Textbook of Family Medicine, 8th Edition

Textbook of Family Medicine EIGHTH EDITION Edited by Robert E. Rakel, MD Professor Department of Family and Community ...

Author: Robert E. Rakel MD | David Rakel MD

753 downloads 4931 Views 62MB Size Report

This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!
Report copyright / DMCA form

DOWNLOAD PDF

Textbook of Family Medicine EIGHTH EDITION Edited by

Robert E. Rakel, MD Professor Department of Family and Community Medicine Baylor College of Medicine Houston, Texas

David P. Rakel, MD Associate Professor Department of Family Medicine University of Wisconsin School of Medicine and Public Health Madison, Wisconsin

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 TEXTBOOK OF FAMILY MEDICINE, EIGHTH EDITION

ISBN: 978-1-4377-1160-8

Copyright © 2011 by Saunders, an imprint of Elsevier Inc. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies, and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/ permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). ISBN: 978-1-4377-1160-8 Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2007, 2002, 1995, 1990, 1984, 1978, 1973 by Saunders. Senior Acquisitions Editor: Kate Dimock Senior Developmental Editor: Agnes Byrnes Publishing Services Manager: Patricia Tannian Senior Project Manager: John Casey Designer: Lou Forgione

Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1

Contributors

Syed M. Ahmed, MD

J. Mark Beard, MD

Professor, Department of Family and Community Medicine Medical College of Wisconsin Milwaukee, Wisconsin Psychosocial Influences on Health

Associate Professor, Department of Family Medicine University of Washington Seattle, Washington Common Office Procedures

Irene Alexandraki, MD, MPH

Wendy S. Biggs, MD

Assistant Professor, Department of Medicine University of Florida College of Medicine Jacksonville, Florida Endocrinology

Associate Professor, Department of Family Medicine Michigan State University College of Human Medicine Lansing, Michigan; Associate Director Midland Family Medicine Residency at MidMichigan Medical Center Midland, Michigan Medical Human Sexuality

Louis F. Amorosa, MD Professor, Department of Medicine University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School New Brunswick, New Jersey Diabetes Mellitus

Gregory J. Anderson, MD Assistant Professor, Department of Family Medicine Mayo Clinic College of Medicine Rochester, Minnesota Obesity

Roberto A. Andrade, MD Assistant Professor, Department of Medicine–Infectious Diseases Baylor College of Medicine Houston, Texas Care of the Adult HIV-Infected Patient

Bruce Bagley, MD Medical Director for Quality Improvement American Academy of Family Physicians Leawood, Kansas Using Health Information Technology for Optimal Patient Care and Service

Bruce Barrett, MD, PhD Associate Professor, Department of Family Medicine University of Wisconsin Madison, Wisconsin Herbs and Other Dietary Supplements

Richard Basilan, MD Infectious Diseases Fellow Department of Internal Medicine University of Missouri Columbia, Missouri Infectious Diseases

Harold Bland, MD Interim Chair, Department of Clinical Sciences Professor and Education Director for Pediatrics Florida State University College of Medicine Tallahassee, Florida Care of the Newborn

John F. Bober, MD Associate Professor of Psychiatry NEOUCOM, Akron Children’s Hospital Akron, Ohio Behavioral Problems in Children and Adolescents

David A. Brechtelsbauer, MD, CMD Associate Professor, Department of Family Medicine Sanford School of Medicine of The University of South Dakota Director of Geriatrics Training Sioux Falls Family Medicine Residency Sioux Falls, South Dakota Delirium and Dementia

Jason N. Buchanan, MD Assistant Professor, Department of Family and Community Medicine Baylor College of Medicine Houston, Texas Gastroenterology

Jennifer J. Buescher, MD, MSPH Associate Director Clarkson Family Medicine Residency Program Omaha, Nebraska Care of the Newborn

v

Contributors

Kara Cadwallader, MD

Frank Verloin DeGruy III, MD, MSFM

Clinical Associate Professor Family Medicine Residency of Idaho University of Washington Department of Family Medicine Seattle, Washington; Medical Director, Planned Parenthood of the Great Northwest–Idaho Boise, Idaho Gynecology

Woodward-Chisholm Chair Department of Family Medicine University of Colorado School of Medicine Aurora, Colorado Difficult Clinical Encounters: Patients with Personality Disorders and Somatoform Complaints

William E. Carroll, MD Adjunct Assistant Professor, Department of Neurology The Ohio State University Medical Center Medical Director, Neurology Grant Medical Center Columbus, Ohio Neurology

Charles Carter, MD Associate Professor, Department of Family Medicine University of South Carolina School of Medicine Residency Director Palmetto Health Family Medicine Residency Program Columbia, South Carolina Urinary Tract Disorders

Douglas Comeau, DO Assistant Professor, Department of Family Medicine Faculty for the Primary Care Sports Medicine Fellowship Boston University School of Medicine Team Physician, Boston College Boston, Massachusetts Rheumatology and Musculoskeletal Problems

Renee Crichlow, MD Assistant Professor North Memorial Family Medicine Residency Program University of Minnesota School of Medicine Minneapolis, Minnesota Preventive Health Care

Earl R. Crouch, Jr, MD Chairman, Department of Ophthalmology Eastern Virginia Medical School Norfolk, Virginia Ophthalmology

Eric R. Crouch, MD Assistant Professor, Departments of Ophthalmology and Pediatrics Eastern Virginia Medical School Norfolk, Virginia Ophthalmology

Alan K. David, MD Professor and Chairman, Department of Family and Community Medicine Associate Dean, Faculty Affairs Medical College of Wisconsin Milwaukee, Wisconsin Hematology

vi

Eric J. Dippel, MD Midwest Cardiovascular Research Foundation Davenport, Iowa Cardiovascular Disease

Jonathan A. Drezner, MD Associate Professor, Department of Family Medicine University of Washington Seattle, Washington Sports Medicine

Denise M. Dupras, MD Assistant Professor of Internal Medicine Department of Internal Medicine Mayo Clinic Rochester, Minnesota Clinical Problem Solving

Bernard Ewigman, MD, MSPH Professor and Chair, Department of Family Medicine University of Chicago Chicago, Illinois Interpreting the Medical Literature: Applying Evidence-Based Medicine in Practice

W. Gregory Feero, MD, PhD Faculty, Maine-Dartmouth Family Medicine Residency Augusta, Maine; Special Advisor to the Director National Human Genome Research Institute National Institutes of Health Bethesda, Maryland Clinical Genetics (Genomics)

Robert E. Feinstein, MD Professor, Department of Psychiatry Senior Associate Dean of Education University of Colorado, School of Medicine Aurora, Colorado Crisis Intervention, Trauma, and Intimate Partner Violence Difficult Clinical Encounters: Patients with Personality Disorders and Somatoform Complaints

Blair Foreman, MD Cardiovascular Medicine Genesis Heart Institute Davenport, Iowa Cardiovascular Disease

Gregory M. Garrison, MD Assistant Professor of Family Medicine Department of Family Medicine Mayo Clinic Rochester, Minnesota Clinical Problem Solving

Contributors

Curtis Gingrich, MD

Donald D. Hensrud, MD, MPH

Clinical Assistant Professor, Department of Family Medicine The Ohio State University College of Medicine Executive Director of Medical Education Grant Medical Center Columbus, Ohio Neurology

Chair, Division of Preventive, Occupational, and Aerospace Medicine Mayo Clinic Associate Professor, Department of Preventive Medicine and Nutrition College of Medicine Rochester, Minnesota Obesity

Andrea Gordon, MD Assistant Professor, Department of Public Health and Family Medicine Tufts University School of Medicine Boston, Massachusetts; Faculty Physician Tufts University Family Medicine Residency Program Malden, Massachusetts Rheumatology and Musculoskeletal Problems

Thomas R. Grant, Jr., MD Faculty, Department of Family and Community Medicine Eastern Virginia Medical School Norfolk, Virginia Ophthalmology

Mary P. Guerrera, MD Associate Professor and Director of Integrative Medicine Department of Family Medicine University of Connecticut School of Medicine Farmington, Connecticut Complementary and Alternative Medicine: Integration into Primary Care

Janelle Guirguis-Blake, MD Clinical Associate Professor, Department of Family Medicine University of Washington Seattle, Washington; Faculty, Department of Family Medicine Tacoma Family Medicine Residency Program Tacoma, Washington Preventive Health Care

Kimberly G. Harmon, MD Clinical Professor Departments of Family Medicine and Orthopaedics and Sports Medicine University of Washington Seattle, Washington Sports Medicine

Kevin Heaton, DO Resident, Department of Family Medicine Boston Medical Center Boston, Massachusetts Rheumatology and Musculoskeletal Problems

Joel J. Heidelbaugh, MD Clinical Associate Professor and Clerkship Director Department of Family Medicine University of Michigan Ann Arbor, Michigan Gastroenterology

Vivian Hernandez-Trujillo, MD Director, Division of Allergy and Immunology Miami Children’s Hospital Miami, Florida Allergy

Arthur H. Herold, MD Associate Professor, Department of Family Medicine College of Medicine University of South Florida Tampa, Florida Interpreting Laboratory Tests

Paul J. Hershberger, PhD Professor, Clinical Health Psychologist Department of Family Medicine Boonshoft School of Medicine Wright State University Dayton, Ohio Psychosocial Influences on Health

Robert Holleman, MD Assistant Professor of Pediatrics University of South Carolina School of Medicine Director, Division of Pediatric Nephrology Residency Director, Palmetto Health Pediatric Residency Program Columbia, South Carolina Urinary Tract Disorders

Keith B. Holten, MD Chief Medical Officer Berger Health System Circleville, Ohio Interpreting the Medical Literature: Applying Evidence-Based Medicine in Practice

Jodi Summers Holtrop, PhD Assistant Professor, Department of Family Medicine College of Human Medicine Michigan State University East Lansing, Michigan Nutrition and Family Medicine

Robert Holleman, MD Assistant Professor, Department of Pediatrics University of South Carolina School of Medicine Director, Division of Pediatric Nephrology Residency Director Palmetto Health Pediatric Residency Program Columbia, South Carolina Urinary Tract Disorders

vii

Contributors

Keith B. Holten, MD

Alicia Kowalhuk, DO

Director, University of Cincinnati–Affiliated Residency Program Clinton Memorial Hospital Wilmington, Ohio Interpreting the Medical Literature: Applying Evidence-Based Medicine in Practice

Assistant Professor, Department of Family and Community Medicine Baylor College of Medicine Medical Director, Insight Program Harris County Hospital District Medical Director, CARE Clinic Santa Maria Hostel Houston, Texas Drug Abuse

Thomas Houston, MD Clinical Professor, Department of Family Medicine and Public Health The Ohio State University Staff Physician, McConnell Heart Health Center Columbus, Ohio Nicotine Addiction

Mark R. Hutchinson, PhD Professor and Director of Sports Medicine Services Department of Orthopaedics College of Medicine, University of Illinois at Chicago Chicago, Illinois Common Issues in Orthopedics

Wayne Jonas, MD Professor, Department of Family Medicine Georgetown University Washington, DC; Associate Professor, Department of Family Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland The Primary Medical Home

Robert B. Kelly, MD, MS Associate Professor, Department of Family Medicine School of Medicine, Case Western Reserve University Faculty, Family Medicine Residency Program Fairview Hospital/Cleveland Clinic Cleveland, Ohio Patient Education

Sanford R. Kimmel, MD Professor and Vice-Chair, Department of Family Medicine University of Toledo College of Medicine Toledo, Ohio Growth and Development

Hoonmo Koo, MD, MPH Assistant Professor, Department of Medicine–Infectious Diseases Baylor College of Medicine Houston, Texas Infectious Diseases

Colin P. Kopes-Kerr, MD, JD, MPH Director of Residency Education, Family Medicine Residency Program Santa Rosa Family Medicine Residency Consortium Physician, Department of Family Medicine Kaiser Permanente Medical Center Santa Rosa, California Lifestyle Interventions and Behavior Change

viii

Jennifer Krejci-Manwaring, MD Assistant Professor, Division of Dermatology and Cutaneous Surgery School of Medicine University of Texas Health Science Center San Antonio, Texas Dermatology

Esther J. Lee, MD Fellow in Endocrinology and Diabetes University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School New Brunswick, New Jersey Diabetes Mellitus

Jeanne P. Lemkau, MD Professor Emerita Department of Family Medicine and Community Health Boonshoft School of Medicine Wright State University Dayton, Ohio Psychosocial Influences on Health

Phil Lieberman, MD Clinical Professor, Departments of Medicine and Pediatrics Division of Allergy and Immunology University of Tennessee College of Medicine Memphis, Tennessee Allergy

Adriana C. Linares, MD, MPH, DrPH Assistant Professor, Department of Family Medicine Baylor College of Medicine Houston, Texas Contraception

David R. McBride, MD Assistant Professor, Department of Family Medicine Boston University School of Medicine Director, Student Health Services Boston University Boston, Massachusetts Infectious Diseases

David McCrary, MD Infectious Disease Fellow, Department of Infectious Diseases University of Missouri Health System Columbia, Missouri Infectious Diseases

Contributors

Stephen P. Merry, MD

Heather L. Paladine, MD

Assistant Professor of Family Medicine Department of Family Medicine Mayo Clinic Rochester, Minnesota Clinical Problem Solving

Assistant Clinical Professor of Medicine Center for Family and Community Medicine Columbia University Medical Center New York, New York Gynecology

David Meyers, MD

Minal Patel, MD

Director, Center for Primary Care, Prevention, and Clinical Partnerships Agency for Healthcare Research and Quality Rockville, Maryland Preventive Health Care

Assistant Professor, Department of Family and Community Medicine Baylor College of Medicine Houston, Texas Back: Cervical and Thoracolumbar Spine

Gregg Mitchell, MD

Gabriella Pridjian, MD

Associate Professor, Department of Family Medicine University of Tennessee Jackson, Tennessee Allergy

Professor and Chair, Department of Obstetrics and Gynecology Tulane University School of Medicine New Orleans, Louisiana Obstetrics

James L. Moeller, MD

David P. Rakel, MD

Sports Medicine Associates, PLC Auburn Hills, Michigan Common Issues in Orthopedics

Associate Professor, Department of Family Medicine University of Wisconsin School of Medicine and Public Health Madison, Wisconsin The Primary Medical Home

Arshag Mooradian, MD Professor and Chair, Department of Medicine University of Florida College of Medicine Jacksonville, Florida Endocrinology

Scott E. Moser, MD Professor, Department of Family and Community Medicine University of Kansas School of Medicine Wichita, Kansas Behavioral Problems in Children and Adolescents

Mary Barth Noel, MPH, PhD, RD Professor and Senior Associate Chair Department of Family Medicine, College of Human Medicine Michigan State University East Lansing, Michigan Nutrition and Family Medicine

John G. O’Handley, MD Clinical Associate Professor, Department of Family Medicine The Ohio State University College of Medicine Columbus, Ohio Otolaryngology

John W. O’Kane, MD Associate Professor, Department of Orthopaedics and Sports Medicine University of Washington Seattle, Washington Sports Medicine

Justin Osborn, MD Clinical Assistant Professor Department of Family Medicine University of Washington Seattle, Washington Common Office Procedures

Robert E. Rakel, MD Professor, Department of Family and Community Medicine Baylor College of Medicine Houston, Texas The Family Physician Care of the Dying Patient Establishing Rapport Nicotine Addiction

Terry G. Rascoe, MD Vice Chair, Department of Family and Community Medicine Texas A&M University College of Medicine Scott & White Memorial Hospital System College Station, Texas Interviewing Techniques

Karen Ratliff-Schaub, MD Associate Professor, Department of Pediatrics The Ohio State University College of Medicine Medical Director, The Nisonger Center for Developmental Disabilities The Ohio State University Columbus, Ohio Growth and Development

Brian C. Reed, MD Assistant Professor and Vice Chair Department of Family and Community Medicine Baylor College of Medicine Houston, Texas Drug Abuse

Michael D. Reis, MD Interim Chair, Department of Family and Community Medicine Texas A&M University College of Medicine Vice Chair, Department of Family Medicine Scott & White Memorial Hospital System College Station, Texas Interviewing Techniques

ix

Contributors

J. Adam Rindfleisch, MD, MPhil

Ann I. Schutt-Ainé, MD

Assistant Professor, Department of Family Medicine University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Herbs and Other Dietary Supplements

Assistant Professor, Department of Obstetrics and Gynecology Baylor College of Medicine Houston, Texas Contraception

R. Hal Ritter, Jr., PhD

Stacy Seikel, MD

Associate Professor, Department of Family and Community Medicine Texas A&M University College of Medicine Family Medicine Residency Behavioral Science Educator Department of Family and Community Medicine Scott & White Memorial Hospital System College Station, Texas Interviewing Techniques

Medical Director The Center For Drug-Free Living Clinical Assistant Professor Department of Psychiatry and Addiction Medicine University of Florida Clinical Assistant Professor Florida State University College of Medicine Orlando, Florida Alcohol Use Disorders

William E. Roland, MD Associate Professor of Clinical Medicine Department of Internal Medicine Division of Infectious Diseases University of Missouri–Columbia School of Medicine Associate Chief of Staff for Education Harry S Truman Memorial Veterans Hospital Columbia, Missouri Infectious Diseases

Brian Rothberg, MD Assistant Professor, Department of Psychiatry University of Colorado Denver School of Medicine Aurora, Colorado Anxiety and Depression

George Rust, MD, MPH Professor, Department of Family Medicine Director, National Center for Primary Care Morehouse School of Medicine Atlanta, Georgia Pulmonary Medicine

Zishan Samiuddin, MD Assistant Professor, Department of Family and Community Medicine Department of Psychiatry and Behavioral Sciences Baylor College of Medicine Houston, Texas Care of the Adult HIV-Infected Patient

Gorge Samraj, MD Associate Professor and Director Family Medicine Obstetrics and Women’s Health Program University of Florida College of Medicine Jacksonville, Florida Endocrinology

Christopher D. Schneck, MD Associate Professor, Department of Psychiatry University of Colorado School of Medicine Aurora, Colorado Anxiety and Depression

Sarina B. Schrager, MD, MS Associate Professor, Department of Family Medicine University of Wisconsin Madison, Wisconsin Gynecology

x

Ashish R. Shah, MD Otolaryngology ENT Ohio ENT Columbus, Ohio Otolaryngology

Krupa Shah, MD, MPH Instructor in Medicine Division of Geriatrics and Aging University of Rochester School of Medicine Rochester, New York Back: Cervical and Thoracolumbar Spine

Nicolas W. Shammas, MS, MD Adjunct Clinical Professor, Department of Internal Medicine University of Iowa School of Medicine Iowa City, Iowa; Midwest Cardiovascular Research Foundation Davenport, Iowa Cardiovascular Disease

Kevin M. Sherin, MD, MPH, MBA Director, Orange County Health Department Clinical Professor of Family Medicine Department of Family Medicine and Rural Health Florida State University College of Medicine Associate Professor, Department of Family Medicine and Department of Education University of Florida Orlando, Florida Alcohol Use Disorders

Jeffrey A. Silverstein, MD Orthopaedic Resident Physician University of Illinois at Chicago Chicago, Illinois Common Issues in Orthopedics

Alan J. Smith, PhD, MEd Assistant Dean and Director Graduate Medical Education Associate Professor of Family Medicine University of Utah Health Sciences Center Salt Lake City, Utah Clinical Problem Solving

Contributors

David A. Smith, MD

Evan J. Tobin, MD

Professor, College of Family and Community Medicine Texas A&M University College of Medicine College Station, Texas Delirium and Dementia

Clinical Assistant Professor Department of Otolaryngology–Head and Neck Surgery The Ohio State University Columbus, Ohio Otolaryngology

Douglas R. Smucker, MD Associate Professor, Department of Family Medicine University of Cincinnati College of Medicine Cincinnati, Ohio Interpreting the Medical Literature: Applying Evidence-Based Medicine in Practice

Abby Snavely, MD Chief Resident, Department of Psychiatry University of Colorado School of Medicine Aurora, Colorado Crisis Intervention, Trauma, and Intimate Partner Violence

James Stallworth, MD Associate Professor, Department of Pediatrics Director, Division of General Pediatrics University of South Carolina School of Medicine Columbia, South Carolina Urinary Tract Disorders

Nancy G. Stevens, MD, MPH Professor, Department of Family Medicine Director, Family Medicine Residency Network University of Washington Seattle, Washington Clinical Genetics (Genomics)

Melissa Stiles, MD Professor, Department of Family Medicine University of Wisconsin Madison, Wisconsin Care of the Elderly Patient

Elizabeth M. Strauch, MD Vice President for Medical Affairs Houston Hospice Houston, Texas Care of the Dying Patient

Jeff Susman, MD Dean and Professor of Family Medicine Northeast Ohio Universities College of Medicine Rootstown, Ohio Interpreting the Medical Literature: Applying Evidence-Based Medicine in Practice

David Swee, MD Professor and Chair Department of Family Medicine University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School New Brunswick, New Jersey Diabetes Mellitus

Peter P. Toth, MD, PhD Clinical Professor Department of Family and Community Medicine University of Illinois School of Medicine Peoria, Illinois; Director of Preventive Cardiology Sterling Rock Falls Clinic Sterling, Illinois Cardiovascular Disease

Richard P. Usatine, MD Professor, Department of Family and Community Medicine and Dermatology School of Medicine, University of Texas Health Science Center San Antonio, Texas Dermatology

William C. Wadland, MD, MS Professor and Chair, Department of Family Medicine College of Human Medicine Michigan State University East Lansing, Michigan Nutrition and Family Medicine

Steven Waldren, MD, MS Director, American Academy of Family Physicians Center for Health Information Technology Leawood, Kansas Using Health Information Technology for Optimal Patient Care and Service

Kathleen Walsh, DO Geriatric Medicine The Monroe Clinic Monroe, Wisconsin Care of the Elderly Patient

Elizabeth A. Warner, MD Associate Professor Department of Internal Medicine University of South Florida Tampa, Florida Interpreting Laboratory Tests

Gloria Westney, MD Associate Professor, Department of Medicine Morehouse School of Medicine Atlanta, Georgia Pulmonary Medicine

Margaret Thompson, MD Associate Professor, Department of Family Medicine College of Human Medicine Michigan State University Grand Rapids, Michigan Nutrition and Family Medicine

xi

Contributors

Russell D. White, MD

Jane E. Wilson, MD, MPH

Professor of Medicine Professor of Orthopedic Surgery Director, Sports Medicine Fellowhip Program Medical Director, Sports Medicine Center Department of Community & Family Medicine University of Missouri Kansas City School of Medicine Head Team Physician, NCAA Division I Athletic Program University of Missouri Kansas City Kansas City, Missouri

Potomac Physicians, P.A. Baltimore, Maryland Preventive Health Care

Dave E. Williams, MD Assistant Professor and Medical Director, Department of Family Medicine Louisiana Health Sciences Center School of Medicine New Orleans, Louisiana Obstetrics

George Wilson, MD Professor and Chair, Department of Community Health and Family Medicine University of Florida College of Medicine Jacksonville, Florida Endocrinology

xii

Tracy Wolff, MD, MPH Medical Officer U.S. Preventive Services Task Force Program Center for Primary Care, Prevention, and Clinical Partnerships Agency for Healthcare Research and Quality Rockville, Maryland Preventive Health Care

Philip Zazove, MD Professor, Department of Family Medicine University of Michigan Health System Ann Arbor, Michigan Clinical Genetics (Genomics)

Anthony Zeimet, DO Assistant Professor of Clinical Medicine Division of Infectious Diseases University of Missouri–Columbia Columbia, Missouri Infectious Diseases

To our wives, Peggy and Denise To all primary care health professionals: Our common goal is to achieve the very best outcome for our patients.

Preface

The Textbook of Family Practice was first published in 1973, just as the new specialty of Family Practice was being established. In 2005 the American Board of Family Practice changed its name to the American Board of Family Medicine, and this eighth edition reflects that name change. For the first time this entire edition is available as an electronic version that can be accessed online. Additional material is available online, including 30 procedural videos from Elsevier’s Procedures Consult. In this edition, David Rakel, Associate Professor of Family Medicine at the University of Wisconsin, joins his father as co-editor. This text is designed to be a resource for family physicians to help them remain current with recent advances in medicine. It will be especially valuable to the family physician preparing for certification or recertification by the American Board of Family Medicine. Our goal is to serve as a resource for all health professionals responsible for providing primary care to patients, especially those professionals who may not have been adequately trained in the large variety of areas that make up comprehensive primary care. Almost all authors are family physicians. For the clinical chapters we have continued the policy established in the

first edition of having an authority in the field co-author the chapter with an experienced family physician to ensure that the information is current and relevant to the needs of the family physician. The use of color in this edition enhances the rapid retrieval of essential information by highlighting Key Points and other essential information. Also included are more than 1000 tables and illustrations. The strength of recommendation taxonomy (SORT) in the Key Treatment boxes is used to indicate the strength of the evidence, focusing primarily on Grade A recommendations. Although this text focuses on problems most frequently encountered by the family physician, significant attention is also paid to the diagnosis of potentially serious problems that would be dangerous if missed. Diagnosing a problem in its early, undifferentiated stage is much more difficult than after symptoms have progressed to the point that the diagnosis is evident. Early diagnosis and treatment decreases morbidity and is much more cost effective. Our thanks to the staff at Elsevier and for their high standards and insistence on quality. Robert E. Rakel, MD David P. Rakel, MD

xv

C H A PTER

1

The Family Physician Robert E. Rakel

Chapter contents The Joy of Family Practice Patient Satisfaction Physician Satisfaction

Development of the Specialty Specialty Certification

Definitions Family Medicine Family Physician Primary Care Primary Care Physician

4 4 4

4 5

5 5 5 5 6

Key Points • T he rewards in family medicine come from knowing patients intimately over time and sharing their trust, respect, and friendship, as well as from the variety of problems encountered in practice that keep the family physician professionally stimulated and challenged. • The American Board of Family Practice was established in 1969 and changed its name to the American Board of Family Medicine in 2004. It was the first specialty board to require recertification every 7 years to ensure ongoing competence of its diplomates. • The American Academy of Family Physicians (AAFP) began as the American Academy of General Practice in 1947 and was renamed in 1971. • Primary care is the provision of continuing, comprehensive care to a population undifferentiated by gender, disease, or organ system. • The most challenging diagnoses are those for diseases or disorders in their early, undifferentiated stage, when there are often only subtle differences between serious disease and minor ailments. • The family physician is the conductor, orchestrating the skills of a variety of health professionals that may be involved in the care of a seriously ill patient. • The most cost-effective health care systems depend on a strong primary care base. The United States has the most expensive health care system in the world but ranks among the worst in overall quality of care because of its weak primary care base. • The greater the number of primary care physicians in a country, the lower is the mortality rate and the lower the cost. ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10001-6

Personalized Care Caring Compassion

Characteristics and Functions of the Family Physician Continuing Responsibility Diagnostic Skills: Undifferentiated Problems The Family Physician as Coordinator

The Family Physician in Practice Practice Content

6 7 7

7 7 12 13

14 14

Patient-Centered Medical Home

15

Looking toward the Future

15

The family physician provides continuing, comprehensive care in a personalized manner to patients of all ages, regardless of the presence of disease or the nature of the presenting complaint. Family physicians accept responsibility for managing an individual’s total health needs while maintaining an intimate, confidential relationship with the patient. Family medicine emphasizes continuing responsibility for total health care—from the first contact and initial assessment through the ongoing care of chronic problems. Prevention and early recognition of disease are essential features of the discipline. Coordination and integration of all necessary health services (minimizing fragmentation) and the skills to manage most medical problems allow family physicians to provide cost-effective health care. Family medicine is a specialty that shares many areas of content with other clinical disciplines, incorporating this shared knowledge and using it uniquely to deliver primary medical care. In addition to sharing content with other medical specialties, family medicine emphasizes knowledge from areas such as family dynamics, interpersonal relations, counseling, and psychotherapy. The specialty’s foundation remains clinical, with the primary focus on the medical care of people who are ill. The curriculum for training family physicians is designed to represent realistically the skills and body of knowledge that the physicians will require in practice. This curriculum is based on an analysis of the problems seen and the skills used by family physicians in their practice. The randomly educated primary physician has been replaced by one specifically prepared to address the types of problems likely to be encountered in practice. For this reason, the “model office” is an essential component of all family practice residency programs.

1

The Family Physician

The Joy of Family Practice

Table 1-1 What Patients Want in a Physician

If you cannot work with love but only with distaste, it is better that you should leave your work and sit at the gate of the temple and take alms from those who work with joy. Kahlil Gibran (1883–1931)

The rewards in family medicine come largely from knowing patients intimately over time and sharing their trust, respect, and friendship. The thrill is the close bond (friendship) that develops with patients. This bond is strengthened with each physical or emotional crisis in a person’s life, when he or she turns to the family physician for help. It is a pleasure going to the office every day and a privilege to work closely with people who value and respect our efforts. The practice of family medicine involves the joy of greeting old friends in every examining room, and the variety of problems encountered keeps the physician professionally stimulated and perpetually challenged. In contrast, physicians practicing in narrow specialties often lose their enthusiasm for medicine after seeing the same problems every day. The variety in family practice sustains the excitement and precludes boredom. Our greatest days in practice are when we are fully focused on our patients, enjoying to the fullest the experience of working with others.

Patient Satisfaction Attributes considered most important for patient satisfaction are listed in Table 1-1 (Stock Keister et al., 2004a). Overall, people want their primary care doctor to meet five basic criteria: “to be in their insurance plan, to be in a location that is convenient, to be able to schedule an appointment within a reasonable period of time, to have good communication skills, and to have a reasonable amount of experience in practice.” They especially want “a physician who listens to them, who takes the time to explain things to them, and who is able to effectively integrate their care” (Stock Keister et al., 2004b, p. 2312). Patient satisfaction correlates strongly with physician satisfaction, and physicians satisfied with their careers are more likely to provide better health care than dissatisfied physicians. If physicians do not enjoy their jobs, their patients are not likely to be happy with these physicians’ job performance.

Physician Satisfaction Physician satisfaction is associated with quality of care, particularly as measured by patient satisfaction. The strongest factors associated with physician satisfaction are not personal income, but rather the ability to provide high-quality care to patients. Physicians are most satisfied with their practice when they can have an ongoing relationship with their patients, the freedom to make clinical decisions without financial conflicts of interest, adequate time with patients, and sufficient communication with specialists (DeVoe et al., 2002). Landon and colleagues (2003) found that rather than declining income, the strongest predictor of decreasing satisfaction 4

• Does not judge. • Understands and supports me. • Is always honest and direct. • Acts as a partner in maintaining my health. • Treats serious and nonserious conditions. • Attends to my emotional as well as physical health. • Truly listens to me. • Encourages me to lead a healthier lifestyle. • Tries to get to know me. • Can help with any problem. • Is someone I can stay with as I grow older. Modified from Stock Keister MC, Green LA, Kahn NB, et al. What people want from their family physician. Am Fam Physician 2004;69:2310.

in practice is loss of clinical autonomy. This includes the inability to obtain services for their patients, control their time with patients, and the freedom to provide high-quality care. In an analysis of 33 specialties, Leigh and associates (2002) found that physicians in high-income “procedural” specialties, such as obstetrics-gynecology, otolaryngology, ophthalmology, and orthopedics, were the most dissatisfied. Physicians in these specialties and those in internal medicine were more likely than family physicians to be dissatisfied with their careers. Among the specialty areas most satisfying was geriatrics. Because the population older than 65 years in the United States has doubled since 1960 and will double again by 2030, it is important that we have sufficient primary care physicians to care for them. The need for and the rewards of this type of practice must be communicated to students before they decide how to spend the rest of their professional lives. Overall, 70% of U.S. physicians are satisfied with their career, with 40% being very satisfied and only 20% dissatisfied (Leigh et al., 2002).

Development of the Specialty As long ago as 1923, Francis Peabody commented that the swing of the pendulum toward specialization had reached its apex, and that modern medicine had fragmented the health care delivery system too greatly. He called for a rapid return of the generalist physician who would give comprehensive, personalized care. Dr. Peabody’s declaration proved to be premature; neither the medical establishment nor society was ready for such a proclamation. The trend toward specialization gained momentum through the 1950s, and fewer physicians entered general practice. In the early 1960s, leaders in the field of general practice began advocating a seemingly paradoxical solution to reverse the trend and correct the scarcity of general practitioners—the creation of still another specialty. These physicians envisioned a specialty that embodied the knowledge, skills, and ideals they knew as primary care. In 1966 the concept of a new specialty in primary care received official recognition in two separate reports published 1 month apart. The first was the report of the Citizens’ Commission on Medical Education of the American Medical Association, also known as the Millis Commission Report.


The second report came from the Ad Hoc Committee on Education for Family Practice of the Council of Medical Education of the American Medical Association, also called the Willard Committee (1966). Three years later, in 1969, the American Board of Family Practice (ABFP) became the 20th medical specialty board. The name of the specialty board was changed in 2004 to the American Board of Family Medicine (ABFM). Much of the impetus for the Millis and Willard reports came from the American Academy of General Practice, which was renamed the American Academy of Family Physicians (AAFP) in 1971. The name change reflected a desire to increase emphasis on family-oriented health care and to gain academic acceptance for the new specialty of family practice.

Specialty Certification The ABFM has distinguished itself by being the first specialty board to require recertification, now called maintenance of certification, every 7 years, to ensure the ongoing competence of its members. In the basic requirements for certification and recertification, the ABFM has included continuing education (CE), the foundation on which the American Academy of General Practice had been built when organized in 1947. A diplomate of the ABFM must complete 300 hours of acceptable CE activity every 6 years and one self-assessment module per year over the Internet to be eligible for recertification. Once eligible, a candidate’s competence is examined by cognitive testing and a performance in practice evaluation. The ABFM’s emphasis on quality of education, knowledge, and performance has facilitated the rapid increase in prestige for the family physician in the U.S. health care system. The logic of the ABFM’s emphasis on continuing education to maintain required knowledge and skills has been adopted by other specialties and state medical societies. All specialty boards are now committed to the concept of recertification to ensure that their diplomates remain current with advances in medicine. The four components of “maintenance of certification” by the ABFM are professional standing, lifelong learning and self-assessment, cognitive expertise, and practice performance assessment. The ABFM also offers subspecialty certificates called certificates of added qualifications in five areas: adolescent medicine, geriatric medicine, hospice and palliative medicine, sleep medicine, and sports medicine. Combined residency programs are available at some institutions combining family medicine and emergency medicine or psychiatry. The combined residency makes candidates available for certification by both specialty boards with 1 year less of training than that required for two separate residencies, through appropriate overlap of training requirements.

Definitions Family Medicine Family medicine is the medical specialty that provides continuing and comprehensive health care for the individual and the family. It is the specialty in breadth that integrates the biologic, clinical, and behavioral sciences. The scope of

family medicine encompasses all ages, both genders, each organ system, and every disease entity (AAFP, 2009). In many countries, the term general practice is synonymous with family medicine. The Royal New Zealand College of General Practitioners emphasizes that a general practitioner provides care that is “anticipatory as well as responsive and is not limited by the age, sex, race, religion, or social circumstances of patients, nor by their physical or mental states.” The general practitioner must be the patient’s advocate; must be competent, caring, and compassionate; must be able to live with uncertainty; and must be willing to recognize limitations and refer when necessary (Richards, 1997).

Family Physician The family physician is a physician who is educated and trained in the discipline of family medicine. Family physicians possess distinct attitudes, skills, and knowledge that qualify them to provide continuing and comprehensive medical care, health maintenance, and preventive services to each member of a family regardless of gender, age, or type of problem (i.e., biologic, behavioral, or social). These specialists, because of their background and interactions with the family, are best qualified to serve as each patient’s advocate in all healthrelated matters, including the appropriate use of consultants, health services, and community resources (AAFP, 2009). The World Organization of Family Doctors (World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians [WONCA]) defines the “family doctor” in part as the physician who is primarily responsible for providing comprehensive health care to every individual seeking medical care, arranging for other health personnel to provide services when necessary. The family physician functions as a generalist who accepts everyone seeking care, whereas other health providers limit access to their services on the basis of age, gender, or diagnosis (WONCA, 1991, p. 2).

Primary Care Primary care is health care that is accessible, comprehensive, coordinated, and continuing. It is provided by physicians specifically trained for and skilled in comprehensive first-contact and continuing care for ill persons or those with an undiagnosed sign, symptom, or health concern (i.e., the “undifferentiated” patient) and is not limited by problem origin (i.e., biologic, behavioral, or social), organ system, or gender. In addition to diagnosis and treatment of acute and chronic illnesses, primary care includes health promotion, disease prevention, health maintenance, counseling, and patient education in a variety of health care settings (e.g., office, inpatient, critical care, long-term care, home care). Primary care is performed and managed by a personal physician, using other health professionals for consultation or referral as appropriate. Primary care is the backbone of the health care system and encompasses the following functions: 1. It is first-contact care, serving as a point of entry for the patient into the health care system. 2. It includes continuity by virtue of caring for patients in sickness and in health over some period. 5

1


3. I t is comprehensive care, drawing from all the traditional major disciplines for its functional content. 4. It serves a coordinative function for all the health care needs of the patient. 5. It assumes continuing responsibility for individual patient follow-up and community health problems. 6. It is a highly personalized type of care. In a 2008 report, Primary Health Care—Now More than Ever, the World Health Organization (WHO) emphasizes that primary care is the best way of coping with the illnesses of the 21st century, and that better use of existing preventive measures could reduce the global burden of disease by as much as 70%. Rather than drifting from one short-term priority to another, countries should make prevention equally important as cure and focus on the rise in chronic diseases that require long-term care and strong community support. Furthermore, at the 62nd World Health Assembly in 2009, WHO strongly reaffirmed the values and principles of primary health care as the basis for strengthening health care systems worldwide.

mary care practice. Rivo and associates (1994) identified the common conditions and diagnoses that generalist physicians should be competent to manage in a primary care practice and compared these with the training of the various “generalist” specialties. They recommended that the training of generalist physicians include at least 90% of the key diagnoses. By comparing the content of residency programs, they found that this goal was met by family practice (95%), internal medicine (91%), and pediatrics (91%), but that obstetrics-gynecology (47%) and emergency medicine (42%) fell far short of this goal.

Primary Care Physician

In the 12th century, Maimonides said, “May I never see in the patient anything but a fellow creature in pain. May I never consider him merely a vessel of disease” (Friedenwald, 1917). If an intimate relationship with patients remains the primary concern of physicians, high-quality medical care will persist, regardless of the way it is organized and financed. For this reason, family medicine emphasizes consideration of the individual patient in the full context of her or his life, rather than the episodic care of a presenting complaint. Family physicians assess the illnesses and complaints presented to them, dealing personally with most and arranging special assistance for a few. The family physician serves as the patients’ advocate, explaining the causes and implications of illness to patients and families, and serves as an advisor and confidant to the family. The family physician receives great intellectual satisfaction from this practice, but the greatest reward arises from the depth of human understanding and personal satisfaction inherent in family practice. Patients have adjusted somewhat to a more impersonal form of health care delivery and frequently look to institutions rather than to individuals for their health care; however, their need for personalized concern and compassion remains. Tumulty (1970) found that patients believe a good physician is one who shows genuine interest in them; who thoroughly evaluates their problem; who demonstrates compassion, understanding, and warmth; and who provides clear insight into what is wrong and what must be done to correct it. Ludmerer (1999a) focused on the problems facing medical education in this environment:

A primary care physician is a generalist physician who provides definitive care to the undifferentiated patient at the point of first contact and takes continuing responsibility for providing the patient’s care. Primary care physicians devote most of their practice to providing primary care services to a defined population of patients. The style of primary care practice is such that the personal primary care physician serves as the entry point for substantially all the patient’s medical and health care needs. Primary care physicians are advocates for the patient in coordinating the use of the entire health care system to benefit the patient (AAFP, 2009). Patients want a physician who is attentive to their needs and skilled at addressing them, and with whom they can establish a lifelong relationship. They want a physician who can guide them through the evolving, complex U.S. health care system. The ABFM and the American Board of Internal Medicine have agreed on a definition of the generalist physician, and they believe that “providing optimal generalist care requires broad and comprehensive training that cannot be gained in brief and uncoordinated educational experiences” (Kimball and Young, 1994, p. 316). The Council on Graduate Medical Education (COGME) and the Association of American Medical Colleges (AAMC) define generalist physicians as those who have completed 3-year training programs in family medicine, internal medicine, or pediatrics and who do not subspecialize. COGME emphasizes that this definition should be “based on an objective analysis of training requirements in disciplines that provide graduates with broad capabilities for primary care practice.” Unfortunately, the number of students entering primary care continues to decline. “In 2009, for the 12th straight year, the number of graduating U.S. medical students choosing primary care residencies reached dismally low levels” (Bodenheimer et al., 2009). Physicians who provide primary care should be trained specifically to manage the problems encountered in a pri6

Personalized Care It is much more important to know what sort of patient has a disease than what sort of disease a patient has. Sir William Osler (1904)

Some managed care organizations have even urged that physicians be taught to act in part as advocates of the insurance payer rather than the patients for whom they care (p. 881). . . . Medical educators would do well to ponder the potential long-term consequences of educating the nation’s physicians in today’s commercial atmosphere in which the good visit is a short visit, patients are “consumers,” and institutional officials speak more often of the financial balance sheet than of service and the relief of patients’ suffering (p. 882).


Cranshaw and colleagues (1995) discussed the ethics of the medical profession: Our first obligation must be to serve the good of those persons who seek our help and trust us to provide it. Physicians, as physicians, are not, and must never be, commercial entrepreneurs, gate closers, or agents of fiscal policy that runs counter to our trust. Any defection from primacy of the patient’s well-being places the patient at risk by treatment that may compromise quality of or access to medical care. . . . Only by caring and advocating for the patient can the integrity of our profession be affirmed (p. 1553).

Caring Caring without science is well-intentioned kindness, but not medicine. On the other hand, science without caring empties medicine of healing and negates the great potential of an ancient profession. The two complement and are essential to the art of doctoring. (Lown, 1996, p. 223)

Family physicians do not just treat patients; they care for people. This caring function of family medicine emphasizes the personalized approach to understanding the patient as a person, respecting the person as an individual, and showing compassion for his or her discomfort. The best illustration of a caring and compassionate physician is “The Doctor” by Sir Luke Fildes (Figure 1-1). The painting shows a physician at the bedside of an ill child in the preantibiotic era. The physician in the painting is Dr. Murray, who cared for Sir Luke Fildes’s son, who died Christmas morning 1877. The painting has become the symbol for medicine as a caring profession.

Compassion The treatment of a disease may be entirely impersonal; the care of a patient must be completely personal. Francis Peabody (1930)

Compassion means co-suffering and reflects the physician’s willingness somehow to share the patient’s anguish and understand what the sickness means to that person. Compassion is an attempt to feel along with the patient. Pellegrino (1979, p. 161) said, “We can never feel with another person when we pass judgment as a superior, only when we see our own frailties as well as his.” A compassionate authority figure is effective only when others can receive the “orders” without being humiliated. The physician must not “put down” the patients, but must be ever ready, in Galileo’s words, “to pronounce that wise, ingenuous, and modest statement—‘I don’t know.’” Compassion, practiced in these terms in each patient encounter, obtunds the inherent dehumanizing tendencies of the current highly institutionalized and technologically oriented patterns of patient care.

Figure 1-1 “The Doctor” by Sir Luke Fildes, 1891. © Tate, London, 2005.

The family physician’s relationship with each patient should reflect compassion, understanding, and patience, combined with a high degree of intellectual honesty. The physician must be thorough in approaching problems but also possess a sense of humor. He or she must be capable of encouraging in each patient the optimism, courage, insight, and the self-discipline necessary for recovery. Bulger (1998) addressed the threats to scientific compassionate care in the managed-care environment: With health care time inordinately rationed today in the interest of economy, Americans could organize themselves right out of compassion. . . . It would be a tragedy, just when we have so many scientific therapies at hand, for scientists to negotiate away the element of compassion, leaving this crucial dimension of healing to nonscientific healers. Time for patient care is becoming increasingly threatened. Bulger (1998, p. 106) described a study involving a “good Samaritan” principle, showing that the decision of whether or not to stop and care for a person in distress is predominantly a function of having the time to do so. Even those with the best intentions require time to be of help to a suffering person.

Characteristics and Functions of the Family Physician The ideal family physician is an explorer, driven by a persistent curiosity and the desire to know more (Table 1-2).

Continuing Responsibility One of the essential functions of the family physician is the willingness to accept ongoing responsibility for managing a patient’s medical care. After a patient or a family has been accepted into the physician’s practice, the responsibility for 7

1


Table 1-2 Attributes of the Family Physician* • A strong sense of responsibility for the total, ongoing care of the individual and the family during health, illness, and rehabilitation. • Compassion and empathy, with a sincere interest in the patient and the family. • A curious and constantly inquisitive attitude. • Enthusiasm for the undifferentiated medical problem and its resolution. • Interest in the broad spectrum of clinical medicine. • The ability to deal comfortably with multiple problems occurring simultaneously in a patient. • Desire for frequent and varied intellectual and technical challenges. • The ability to support children during growth and development and in their adjustment to family and society. • Assists patients in coping with everyday problems and in maintaining stability in the family and community. • The capacity to act as coordinator of all health resources needed in the care of a patient. • Enthusiasm for learning and for the satisfaction that comes from maintaining current medical knowledge through continuing medical education. • The ability to maintain composure in times of stress and to respond quickly with logic, effectiveness, and compassion. • A desire to identify problems at the earliest possible stage or to prevent disease entirely. • A strong wish to maintain maximum patient satisfaction, recognizing the need for continuing patient rapport. • The skills necessary to manage chronic illness and to ensure maximal rehabilitation after acute illness. • Appreciation for the complex mix of physical, emotional, and social elements in personalized patient care. • A feeling of personal satisfaction derived from intimate relationships with patients that naturally develop over long periods of continuous care, as opposed to the short-term pleasures gained from treating episodic illnesses. • Skills for and a commitment to educating patients and families about disease processes and the principles of good health. • A commitment to place the interests of the patient above those of self. *These characteristics are desirable for all physicians, but are of greatest importance for the family physician.

care is total and continuing. The Millis Commission chose the term “primary physician” to emphasize the concept of primary responsibility for the patient’s welfare; however, the term primary care physician is more popular and refers to any physician who provides first-contact care. The family physician’s commitment to patients does not cease at the end of illness but is a continuing responsibility, regardless of the patient’s state of health or the disease process. There is no need to identify the beginning or end point of treatment, because care of a problem can be reopened at any time—even though a later visit may be primarily for another problem. This prevents the family physician from focusing too narrowly on one problem and helps maintain a perspective on the total patient in her or his environment. Peabody (1930) believed that much patient dissatisfaction resulted from the physician’s neglecting to assume personal responsibility for supervision of the patient’s care: “For some reason or other, no one physician has seen the case through from beginning to end, and the patient may be suffering from the very multitude of his counselors” (p. 8). Continuity of care is a core attribute of family medicine, transcending multiple illness episodes, and it includes 8

responsibility for preventive care and care coordination. “This longitudinal relationship evolves into a strong bond between physician and patient characterized by trust, loyalty, and a sense of responsibility” (Saultz, 2003). Trust grows stronger as the physician-patient relationship continues and provides the patient a sense of confidence that care will always be in his or her best interest. It also facilitates improved quality of care the longer the relationship continues. The greater the degree of continuing involvement with a patient, the more capable the physician is in detecting early signs and symptoms of organic disease and differentiating it from a functional problem. Patients with problems arising from emotional and social conflicts can be managed most effectively by a physician who has intimate knowledge of the individual and his or her family and community background. This knowledge comes only from insight gained by observing the patient’s long-term patterns of behavior and responses to changing stressful situations. This longitudinal view is particularly useful in the care of children and allows the physician to be more effective in assisting children to reach their full potential. The closeness that develops between physicians and young patients increases a physician’s ability to aid the patients with problems later in life, such as adjustment to puberty, problems with employment, or marriage and changing social pressures. As the family physician maintains this continuing involvement with successive generations within a family, the ability to manage intercurrent problems increases with knowledge of the total family background. By virtue of this ongoing involvement and intimate association with the family, the family physician develops a perceptive awareness of a family’s nature and style of operation. This ability to observe families over time allows valuable insight that improves the quality of medical care provided to an individual patient. A major challenge in family medicine is the need to be alert to the changing stresses, transitions, and expectations of family members over time, as well as the effect that these and other family interactions have on the health of individual patients. Although the family is the family physician’s primary concern, his or her skills are equally applicable to the individual living alone or to people in other varieties of family living. Individuals with alternative forms of family living interact with others who have a significant effect on their lives. The principles of group dynamics and interpersonal relationships that affect health are equally applicable to everyone. The family physician must assess an individual’s personality so that presenting symptoms can be appropriately evaluated and given the proper degree of attention and emphasis. A complaint of abdominal pain may be treated lightly in one patient who frequently presents with minor problems, but the same complaint would be investigated immediately and in depth in another patient who has a more stoic personality. The decision regarding which studies to perform and when is influenced by knowledge of the patient’s lifestyle, personality, and previous response pattern. The greater the degree of knowledge and insight into the patient’s background, as gained through years of ongoing contact, the more capable is the physician in making an appropriate early and rapid assessment of the presenting complaint. The less background information the physician has to rely on, the greater is the need to depend on costly laboratory studies, and the more likely is overreaction to the presenting symptom.


Families receiving continuing comprehensive care have a decreased incidence of hospitalization, fewer operations, and less physician visits for illnesses compared with those having no regular physician. This results from the physician’s knowledge of the patients, seeing them earlier for acute problems and therefore preventing complications that would require hospitalization, being available by telephone or by e-mail, and seeing them more frequently in the office for health supervision. Care is also less expensive because there is less need to rely on radiographic and laboratory procedures and visits to emergency departments. Continuity of care improves quality of care, especially for those with chronic conditions such as asthma and diabetes (Cabana and Jee, 2004). Because about 90% of diabetic patients in the United States receive care from a primary care physician, continuity of care can be especially important. Parchman and associates (2002) found that for adults with type 2 diabetes, continuing care from the same primary care provider was associated with lower HbA1c values, regardless of how long the patient had suffered from diabetes. Having a regular source of primary care helped these adults manage their diet and improve glucose control.

Collusion of Anonymity The need for a primary physician who accepts continuing responsibility for patient care was emphasized by Michael Balint (1965) in his concept of collusion of anonymity. In this situation the patient is seen by a variety of physicians, not one of whom is willing to accept total management of the problem. Important decisions are made—some good, some poor—but without anyone feeling fully responsible for them. Francis Peabody (1930) examined the futility of a patient’s making the rounds from one specialist to another without finding relief because the patient: . . . lacked the guidance of a sound general practitioner who understood his physical condition, his nervous temperament and knew the details of his daily life. And many a patient who on his own initiative has sought out specialists, has had minor defects accentuated so that they assume a needless importance, and has even undergone operations that might well have been avoided. Those who are particularly blessed with this world’s goods, who want the best regardless of the cost and imagine that they are getting it because they can afford to consult as many renowned specialists as they wish, are often pathetically tragic figures as they veer from one course of treatment to another. Like ships that lack a guiding hand upon the helm, they swing from tack to tack with each new gust of wind but get no nearer to the Port of Health because there is no pilot to set the general direction of their course (pp. 21-22).

Chronic Illness The family physician must also be committed to managing the common chronic illnesses that have no known cure, but for which continuing management by a personal physician is all the more necessary to maintain an optimal state of health for the patient. It is a difficult and often trying job to manage

these unresolvable and progressively crippling problems, control of which requires a remodeling of the lifestyle of the entire family. About 45% of Americans have a chronic condition. The costs to individuals and to the health care system are enormous. In 2000, care of chronic illness consumed 75 cents of every health care dollar spent in the United States (Robert Wood Johnson Foundation Annual Report, 2002). Comorbidity, the coincident occurrence of coexisting and apparently unrelated disorders, is increasing as the population ages. Those age 60 years or older have an average of 2.2 chronic conditions, and physicians in primary care provide most of this care (Bayliss et al., 2003). Diabetes is one of the most rapidly increasing chronic conditions (Figure 1-2). Quality of life is enhanced when care of diabetic patients is provided in a primary care setting without compromising quality of care (Collins et al., 2009).

Quality of Care Primary care provided by physicians specifically trained to care for the problems presenting to personal physicians, who know their patients over time, is of higher quality than care provided by other physicians. This has been confirmed by a variety of studies comparing the care given by physicians in different specialties. When hospitalized patients with pneumonia are cared for by family physicians or full-time specialist hospitalists, the quality of care is comparable, but the hospitalists incur higher hospital charges, longer lengths of stay, and use more resources (Smith et al., 2002). In the United States, a 20% increase in the number of primary care physicians is associated with a 5% decrease in mortality (40 fewer deaths per 100,000 population), but the benefit is even greater if the primary care physician is a family physician. Adding one more family physician per 10,000 people is associated with 70 fewer deaths per 100,000 population, which is a 9% reduction in mortality. Specialists practicing outside their area have increased mortality rates for patients with acquired pneumonia, acute myocardial infarction, congestive heart failure, and upper gastrointestinal hemorrhage. Specialists are trained to look for zebras instead of horses, and specialty care usually means more tests, which lead to a cascade effect and a greater likelihood of adverse effects, including death. A study of the major determinants of health outcomes in all 50 U.S. states found that when the number of specialty physicians increases, outcomes are worse, whereas mortality rates are lower where there are more primary care physicians (Starfield et al., 2005). McGann and Bowman (1990) compared the morbidity and mortality of patients hospitalized by family physicians and by internists. Even though the family physicians’ patients were older and more severely ill, there was no significant difference in morbidity and mortality. The total charges for their hospital care also were lower. A comparison of family physicians and obstetrician-gynecologists in the management of low-risk pregnancies showed no difference with respect to neonatal outcomes. However, women cared for by family physicians had fewer cesarean sections and episiotomies and were less likely to receive epidural anesthesia (Hueston et al., 1995). Patients of subspecialists practicing outside their specialty have longer lengths of hospital stay and higher mortality 9

1

The Family Physician 30

28.1 1995 2005

Percent of visits

25 20

19.9 18.2

17.5

15 11.9

10.4

10 6.0 5 0.7

7.8

7.3

8.7 8.3

4.9

1.5

0 Arthritis

Chronic renal COPD1,2 failure1

Depression1 Diabetes1 Hypertension1 Obesity1 Chronic condition

1Significant difference in percentages between 1995 2COPD, Chronic obstructive pulmonary disease.

and 2005 (p 8%

70–79

>12%

70–79

>11%

*Level at which the number of cardiovascular disease events prevented is closely balanced to the number of serious bleeding events. Shared decision making is strongly encouraged with persons whose risk is close to (either above or below) these estimates of 10-year risk levels. As the potential cardiovascular disease reduction benefit increases above harms, the recommendation to take aspirin should become stronger.

84

adults continued to smoke (CDC, 2008b). The prevalence of smoking is higher among certain subgroups, including Native Americans and Native Alaskans, those with a lower level of education, adults age 25 to 44, and people living below the poverty level (CDC, 2008b).

Screening and Identification of Risk Group Clinics that implement screening systems designed to identify and document a patient’s tobacco use status increase the rate at which clinicians intervene with their patients who smoke. Including tobacco use as a “vital sign” increases the probability that tobacco use is routinely assessed and addressed. However, there is limited evidence that a screening system has a substantial impact on tobacco cessation rates (Fiore et al., 2008).

Effectiveness of Counseling Intervention The optimal duration and frequency of tobacco counseling interventions is unknown, but good evidence indicates that even brief counseling interventions (80%) and specificity (>99%) and can be used with urine, vaginal, and cervical swabs (Meyers et al., 2007). It is important to remember that even with a test with high sensitivity, in a low-prevalence population, a positive screening result is more likely to be a false positive than an actual case. When screening a 20-yearold woman with no other risk factors other than her young age, given a prevalence rate of 1%, the positive predictive value for a positive chlamydial screen with an NAAT is only 47%. Point-of-care tests are becoming available that can be conducted in the office setting in about 30 minutes. Their sensitivity remains substantially lower than for laboratoryconducted NAATs, although their specificity is high (Mahilum-Tapay et al., 2007).

Effectiveness of Early Detection and Intervention Screening and treatment for Chlamydia infection in highrisk, asymptomatic women has been demonstrated to reduce significantly their incidence of PID after 12 months of follow-up. There have been no published studies of the effectiveness of screening women not at increased risk. Although treatment of men eradicates infection, there is no evidence that screening men reduces transmission, acute infection, or sequelae in women. Potential harms of screening and treatment include the effects of false-positive test results, patient anxiety, unnecessary antibiotic use, and adverse drug reactions (Meyers et al., 2007).

Recommendation The USPSTF recommends that clinicians routinely screen all sexually active women age 24 or younger (including pregnant women) and older asymptomatic women at increased risk for chlamydial infection. They recommend against routine screening in asymptomatic women age 25 and older (including pregnant women) who are not at increased risk. Although USPSTF found insufficient evidence to recommend for or against routine screening of men, they counsel clinicians and health care systems to focus on improving screening rates among women at increased risk, a group for whom the benefits of screening are certain (USPSTF, 2007).

Preventive Health Care

The AAFP (2009) concurs with USPSTF. The CDC (2006) recommends annual screening for sexually active women 25 years old and younger and older women with new or multiple sexual partners. Women with asymptomatic untreated chlamydial infection have high rates of morbidity from PID and its sequelae. Screening tests can accurately detect chlamydial infection in those at risk, and treatment is effective. All sexually active women age 24 and younger and all older women at increased risk for PID should be screened for chlamydial infection. The same risk factors and recommendation applies to pregnant women (USPSTF, 2007).

Gonorrheal Infection Burden of Disease In 2006, infection with Neisseria gonorrhoeae was the second most common reportable disease in the United States, with a reported rate just under 119 cases per 100,000 population. Unlike Chlamydia infection, which has seen increasing rates over the past decade, rates of N. gonorrhoeae infection have been stable since the mid-1990s. Infection rates are highest among girls and women between ages 15 and 24 years and men between 20 and 24 years. Although rates are increasing among white and Hispanic populations, the rate among blacks in 2006 (663 cases per 100,000) was almost 20 times higher than for whites. Other risk factors for infection include a history of previous gonorrhea or other STI, new or multiple sexual partners, inconsistent condom use, sex work, and drug use. The prevalence of gonorrhea varies widely among regions of the United States, with the South and Midwest having notably higher rates than the Northeast and West, and among communities (CDC, 2007). In women, infection with N. gonorrhoeae is a major cause of cervicitis and PID. PID may cause ectopic pregnancy, infertility, and chronic pelvic pain. In men, gonorrhea can result in urethritis, epididymitis, and prostatitis. Gonorrheal infection is frequently asymptomatic in women. Infection in men can be asymptomatic as well, but less often than in women (Glass et al., 2005b).

Accuracy of Screening Tests Culture isolates collected from endocervical swabs in women and urethral swabs in men remain an accurate screening test for genital gonorrheal infection. When transport conditions are suitable, the sensitivity is higher than 90%. Because culture remains the “gold standard,” the specificity of culture is 100% when culture isolates are speciated. NAATs and nucleic acid hybridization tests have demonstrated sensitivity and specificity comparable to culture and compare better when transport conditions are not suitable for culture. Some newer tests can be used with urine and vaginal swabs, allowing screening without an invasive procedure (Glass et al., 2005b).

Effectiveness of Early Detection and Intervention Screening can accurately detect gonorrheal infection, and antibiotic therapy can eliminate urogenital infections, prevent complications, and prevent further transmission. Potential harms of screening and treatment include false-positive test results, anxiety, and unnecessary antibiotic use (Glass et al., 2005b).

Recommendation The USPSTF recommends that clinicians screen all sexually active women who are at increased risk for gonorrheal infection. Because of the lower burden of undiagnosed and untreated genital gonorrheal infection in men than women, USPSTF concluded that there was insufficient evidence to recommend for or against routine screening for gonorrhea in men at increased risk for infection. They recommend against routine screening for gonorrhea in men and women who are at low risk for infection (USPSTF, 2005). Unlike chlamydial infection, which is relatively evenly distributed across the United States, gonorrheal infection demonstrates marked regional and local variation. USPSTF recommends that clinicians and health systems work with public health officials to understand the prevalence and distribution of gonorrhea in their communities and adjust their screening practices accordingly. The AAFP and ACOG recommend screening sexually active women, including adolescents, at high risk for gonorrhea. The CDC recommends that clinicians screen all sexually active men who have sex with men for genital gonorrhea at least annually and for rectal and pharyngeal gonorrhea if they are at risk due to exposure. The Infectious Disease Society of America (IDSA) recommends that all HIV-positive individuals be screened for gonorrhea (Glass et al., 2005b). Women with asymptomatic gonorrheal infection have high rates of morbidity from PID and its sequelae. Screening tests can accurately detect gonorrheal infection in those at risk, and treatment is effective. All high-risk, sexually active women (including pregnant women) should be screened for gonorrheal infection (USPSTF, 2005).

Human Immunodeficiency Virus Infection Burden of Disease. In 2007, about 37,000 people in the United States were diagnosed with acquired immunodeficiency syndrome (AIDS), raising the total to more than 1 million diagnosed cases since the recognition of AIDS in 1981. In 2006, more than 450,000 people in the United States were living with AIDS, and an additional 56,300 people were newly infected with HIV. From 2003 to 2007, the total number of new AIDS cases has remained relatively stable, but the proportion of HIV/ AIDS cases has continued to increase steadily (CDC, 2009). With approximately 12,000 deaths in 2007, AIDS is not in the top 15 causes of death in the United States (Heron et al., 2009). Those at increased risk for HIV infection include men who have had sex with men after 1975; men and women having unprotected sex with multiple partners; past or present injection drug users; men and women who exchange sex for money or drugs or have sex partners who do; individuals whose past or present sex partners were HIV infected, bisexual, or injection drug users; persons being treated for STIs; and persons with a history of blood transfusion between 1978 and 1985. Persons who request an HIV test despite reporting no individual risk factors may also be considered at increased risk, because this group is likely to include individuals not willing to disclose high-risk behaviors. A higher prevalence is seen in high-risk settings, such as STI clinics, correctional facilities, 87

6


homeless shelters, tuberculosis clinics, clinics serving men who have sex with men, and adolescent health clinics with a high prevalence of STIs (Chou et al., 2005).

Metabolic, Nutritional, and Endocrine Conditions

Accuracy of Screening Tests

Type 2 Diabetes Mellitus Burden of Disease

Standard testing for HIV infection with the repeatedly reactive enzyme immunoassay, followed by confirmatory Western blot or immunofluorescent assay, has a sensitivity and specificity greater than 99%. False-positive test results are rare, even in low-risk settings. Compared with standard HIV testing, the reported sensitivities of rapid tests on blood specimens range from 96% to 100%, with specificities greater than 99.9%. Reported sensitivities and specificities of oral fluid HIV tests are also high (>99%) (Chou et al., 2005).

Effectiveness of Early Detection and Intervention The wide adoption in the late 1990s of the use of highly active antiretroviral therapy (HAART) regimens with three or more agents has been associated with a marked decline in morbidity and mortality for HIV-infected patients in the United States. HAART regimens are consistently effective in reducing clinical progression and mortality in persons with CD4 cell counts less than 200 cells/mm3. Appropriate prophylaxis and immunization against certain opportunistic infections have also been effective interventions in reducing morbidity (Chou et al., 2005). Because false-positive test results are rare, harms associated with HIV screening are minimal. Potential harms of truepositive test results include increased anxiety, labeling, and deleterious effects on close relationships. Although it is hoped that early diagnosis may lead to decreased transmission of HIV, evidence is lacking on the effect of increased screening leads on transmission (Chou et al., 2007). Additional evidence is also needed to clarify the balance of benefits and harms of early versus delayed treatment of asymptomatic patients with HIV infection.

Recommendation The USPSTF strongly recommends that clinicians screen for HIV in all adolescents and adults at increased risk for HIV infection. They make no recommendation for or against routinely screening for HIV in adolescents and adults who are not at increased risk for HIV infection (USPSTF, 2005). Counseling and HIV testing of high-risk individuals are recommended by the CDC and numerous professional organizations, including the AAFP, AMA, ACOG, ACP, and IDSA. The AAP considers all sexually active adolescents to be a highrisk group and recommends they be counseled and offered HIV testing. The CDC recommends that routine, voluntary testing be offered to all patients seen in health care facilities where the prevalence of HIV infection is 1% or greater and in settings serving client populations at increased behavioral or clinical HIV risk (Chou et al., 2005). Standard and FDA–approved rapid screening tests accurately detect HIV infection, and interventions (e.g., HAART) reduce the risk of clinical progression and premature death. HIV screening should be offered to all adolescents and adults at high risk for HIV infection (USPSTF, 2005). The following topics are discussed online at www.expertconsult.com: • Syphilis infection • Recommendations against routine screening for hepatitis B, C, and herpesvirus infections. 88

The prevalence of type 2 diabetes in the United States is rising, particularly among adults with a body mass index (BMI) of 35 kg/m2 or greater. From 1980 through 2006, the number of Americans with diabetes tripled, from 5.6 to 16.8 million (Norris et al., 2008). Patients with type 2 diabetes are at increased risk for microvascular and macrovascular disease. Microvascular disease leads to high rates of blindness, endstage renal disease, and lower extremity amputations; macrovascular disease accounts for twofold to fourfold increased risk for heart disease and stroke in people with diabetes.

Accuracy of Screening Tests Three tests have been used to screen for diabetes: fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2-hour PG), and hemoglobin A1c (HbA1c). Sensitivity and specificity are in the range of 75% to 80% for all three tests using these thresholds: FPG = 126 mg/dL, 2-hour PG = 200 mg/dL, and HbA1c = 6.4% (Harris et al., 2002). The American Diabetes Association (ADA) has recommended the FPG or 2-hour PG test for screening; the FPG is easier and faster to perform, more convenient, and acceptable to patients, and it is less expensive than other screening tests. The FPG is also more reproducible than the 2-hour PG test and has less intraindividual variation.

Effectiveness of Early Detection and Intervention Early detection of diabetes has the potential to prevent complications of diabetes through early intensive control of cardiovascular disease risk factors and tight glycemic control. Aggressive blood pressure control in those identified with diabetes reduces the incidence of cardiovascular events and cardiovascular mortality. Patients with hyperlipidemia and diabetes who are treated with lipid-lowering agents have a similar reduction in the incidence of coronary heart disease (CHD) events as those without diabetes (RR reduction, 19%42%) (USPSTF, 2008). Intensive glycemic control in persons with clinically detected diabetes can reduce progression of microvascular disease. The benefits of tight glycemic control on microvascular clinical outcomes, such as severe visual impairment or end-stage renal disease, require long-term follow-up. There is inadequate evidence that early diabetes control as a result of screening provides an incremental benefit for microvascular clinical outcomes compared with initiating treatment after clinical diagnosis (USPSTF, 2008). In patients who are screened and identified to have prediabetes, evidence indicates that lifestyle and pharmacotherapy can delay the progression of diabetes. However, there is little direct evidence that identifying persons with prediabetes will lead to long-term health benefits. Aggressive blood pressure control and lipid treatment therapy in patients with type 2 diabetes have been shown to reduce the incidence of CHD events in patients with diabetes (USPSTF, 2008). Potential harms of screening include psychological distress from a false-positive diagnosis and earlier exposure to potential adverse effects of treatment than if the diagnosis were made clinically.


Recommendation The USPSTF (2008) recommends screening for type 2 diabetes in asymptomatic adults with sustained blood pressure (either treated or untreated) greater than 135/80 mm Hg. AAFP (2009) concurs with this recommendation. ACOG recommends FPG testing for women beginning at age 45 years, with an interval of 3 years. On the basis of expert opinion, ADA recommends screening every 3 years to detect prediabetes (IFG or IGT) or diabetes in persons age 45 and older, particularly in those with BMI of 25 kg/m2 or greater. Screening is recommended in those overweight individuals younger than 45 years with one additional risk factor, including inactivity, family history of type 2 diabetes mellitus, membership in a high-risk ethnic group, gestational diabetes, hypertension, dyslipidemia, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), or a history of vascular disease (ADA, 2009).

Osteoporosis in Postmenopausal Women Burden of Disease One half of all postmenopausal women will have an osteoporosis-related fracture in their lifetime, including 25% who will develop a vertebral deformity and 15% who will suffer a hip fracture. Osteoporosis is defined as a bone mineral density (BMD) more than 2.5 standard deviations (SD) below the mean for a healthy woman, and osteopenia is a BMD between 1 and 2.5 SD below the mean. Among white women, it is estimated that 41% older than age 50 have osteopenia, and that 15% between ages 50 and 59 and 70% of those older than 80 have osteoporosis. Mexican American women experience similar rates. The rate among black women is approximately one-half the rate of the other groups. Including all races in the United States, an estimated 14 million women older than 50 years have osteopenia, and 5 million have osteoporosis (Nelson and Helfand, 2002).

Accuracy of Screening Tests There are two major components of screening for osteoporosis: assessment of risk factors and BMD measurement. Older age, low body mass index (BMI), and not using estrogen replacement are associated with increased risk of osteoporosis and fracture. Other risk factors include white or Asian ancestry, positive family history, tobacco use, and low levels of weight-bearing physical activity (Melton et al., 1989). The WHO FRAX is a common assessment tool.* Other specific instruments, such as the Osteoporosis Risk Assessment Instrument (ORAI) and the Simple Calculated Osteoporosis Risk Estimation (SCORE) tool, use these risk factors to identify women at increased risk for fracture or low BMD. The ORAI has sensitivity of 94% and specificity of 41%, and the SCORE has sensitivity of 91% and specificity of 40% (Nelson and Helfand, 2002). The BMD measured at the femoral neck by dual-energy x-ray absorptiometry (DEXA) is the most validated predictor of hip fractures. Several other methods for measuring BMD include single-photon absorptiometry, ultrasound, quantitative CT, single-energy x-ray absorptiometry, and peripheral quantitative CT. The results between tests are not highly correlated with one another, and the likelihood of a diagnosis of osteoporosis varies greatly depending on the site and type *www.shef.ac.uk/FRAX/tool.jsp?locationValue=1

of test used, number of sites tested, brand of densitometer, and relevance of the reference range.

Effectiveness of Early Detection and Intervention Treating osteoporosis with bisphosphonates reduces the risk of fracture (Nelson and Helfand, 2002). Estrogen, calcitonin, and selective estrogen receptor modulators have also been used to increase bone density and reduce fractures. The benefits of these treatments are greater for women at high risk for fracture than women at lower risk. Benefits of screening increase substantially with older age, particularly for women older than 65 and for women with important risk factors. In women age 60 to 64 who have risk factors, the benefits of screening are comparable to those of women age 65 to 69. Several potential harms are associated with screening and treatment. An unwarranted diagnosis of osteoporosis may provoke anxiety. Potential harms may also arise from misinterpretation of BMD tests. Patients may have side effects from the medication; bisphosphonates often cause gastrointestinal side effects. The cost and inconvenience of undergoing multiple confirmatory tests must be considered.

Recommendation The USPSTF (2011) recommends that women age 65 or older be routinely screened for osteoporosis, and that routine screening begin in younger women whose fracture risk equals that of a 65-year-old woman without risk factors. AAFP supports this position. The National Osteoporosis Foundation (NOF, 2008) recommends that adults over age 50 receive 1200 mg of calcium and 800 to 1000 IU of vitamin D3 daily. NOF recommends BMD screening in women age 65 and older and men age 70 and older, as well as in postmenopausal women and men age 50 to 69 based on their risk factor profile. ACOG endorses the NOF guidance.

Obesity Burden of Disease Obesity is a substantial health problem in the United States, and the percentage of the population who is overweight or obese continues to rise. Defined as a BMI of 30 or higher, the prevalence of obesity in adults in the United States has increased from 13% to 27% over the past 40 years (McTigue et al., 2003). The prevalence of overweight rose from 31% to 34%. Obesity and overweight are associated with an increased risk of CHD, hypertension, stroke, type 2 diabetes, sleep apnea, musculoskeletal disorders, gallbladder disease, and several types of cancer. Obesity is associated with a decreased quality of life and social stigmatization.

Accuracy of Screening Tests The BMI (weight [kg] ÷ height [m2]) is the most common test for obesity screening. It is easy to measure, highly reliable, and highly correlated with body fat and body fat mass. The waist-to-hip ratio is a good predictor of cardiovascular morbidity and mortality (McTigue et al., 2003). However, the BMI has been linked with the broadest range of health outcomes and is the most common indicator used in trials.

Effectiveness of Early Detection and Intervention Counseling and behavioral interventions produce small to modest degrees of weight loss sustained over at least 1 year (McTigue et al., 2003). High-intensity or more 89

6


f requent counseling promotes greater weight loss than low-intensity counseling. Moderate intentional weight loss (5%-10% of body weight) decreases the severity of the comorbidities associated with obesity and may reduce mortality. Pharmacotherapy also promotes modest weight loss (3-5 kg); discontinuing the medication may lead to rapid regain. Obesity surgery has been performed on patients with a BMI greater than 40 or with obesity-related comorbidities and has achieved dramatic weight loss. Potential harms associated with screening and treatment include the stigma of being labeled “obese” and the detrimental health effects from cycles of weight loss followed by regain. Medications may cause adverse effects, and their long-term safety is not well known. A patient undergoing surgery may have complications, and 25% require reoperation within 5 years (McTigue et al., 2003).

Recommendation The USPSTF (2003) recommends that clinicians screen all adult patients for obesity and offer intensive counseling and behavioral interventions to promote sustained weight loss for obese patients. AAFP (2008) concurs with this recommendation.

Healthy Diet Counseling Burden of Disease Consuming a healthy diet lowers the risks of morbidity and mortality from chronic disease. Four of the 10 leading causes of death—CHD, some types of cancer, stroke, and type 2 diabetes mellitus—are associated with unhealthy diets (Ammerman et al., 2002). Despite well-established benefits of consuming a healthy diet, more than 80% of Americans of all ages eat fewer than the recommended number of daily servings of fruit, vegetables, and grain products. Also, they consume more than the recommended number of calories from saturated fat and total fat (USDHHS, 2000).

Accuracy of Screening Tests Several brief, validated dietary assessment instruments can identify dietary counseling needs, guide intervention, and monitor change among adult patients in primary care settings. (These can be found in the article at http://escholarship. org/uc/item/9s03p43r jgb.) Most of these instruments can be self-administered, are easily scored, have fewer than 40 items, and take 10 minutes or less to administer. Most assessments are subject to bias and may result in underreporting of calories.

Effectiveness of Early Detection and Intervention. Medium- to high-intensity behavioral interventions produce consistent, sustained, and clinically important changes in dietary intake of saturated fat, total fat, fruits, vegetables, and fiber. The most effective interventions generally combine education, behaviorally oriented counseling, and patient reinforcement and follow-up (Ammerman et al., 2002). More intensive interventions and those of longer duration are associated with greater benefits and more sustained changes in diet. Selfreported dietary changes are often accompanied by improved lipids, BMI, and weight. Patients with hyperlipidemia and other risk factors for CHD and diet-related chronic disease benefit the most from dietary counseling, whereas patients at average risk for chronic disease generally achieve smaller changes in diet. 90

Recommendation The USPSTF (2003) recommends intensive behavioral counseling for all adults with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease. Counseling may be done by the primary care provider or through referral to a specialist. The AAFP (2008) recommends intensive behavioral dietary counseling for adult patients with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease.

Physical Activity Counseling Burden of Disease Sedentary lifestyles are associated with increased risks of chronic diseases, including CHD, diabetes, obesity, and osteoporosis, and increased physical activity can reduce those risks (USDHHS, 2000). Despite the well-established benefits of exercise, only about 20% of adults achieved the recommended Healthy People 2010 level of moderate exercise: 30 minutes of moderate physical activity on most days of the week; only 15% achieved a vigorous level of physical activity for 20 minutes on 3 days of the week (Eden et al., 2002).

Effectiveness of Counseling Existing studies on physical activity counseling are inadequate to determine the overall efficacy, effectiveness, and feasibility of counseling in a primary care setting. Combining provider counseling with behavioral interventions such as patient goal setting, written exercise prescriptions, and individually tailored physical activity regimens may be the most effective way to change physical activity levels and warrants more research. Linking patients to community-based physical activity and fitness programs may enhance the effectiveness of primary care clinician counseling (Eden et al., 2002).

Recommendation The USPSTF (2002) states that the evidence is insufficient to recommend for or against behavioral counseling in primary care settings to promote physical activity. Organizations that include the AAFP, U.S. Department of Health and Human Services (Healthy People 2010), CDC, AAP, American Heart Association (AHA), and ACOG recommend that health care providers counsel all individuals about physical activity. These recommendations are based on the known health benefits of physical activity rather than on the effectiveness of counseling for promoting changes in physical activity (Eden et al., 2002). Hormone therapy for the prevention of chronic conditions in postmenopausal women is discussed online at www. expertconsult.com.

Special Populations Preventive Services for Children and Adolescents Challenges in Evidence-Based Prevention Prevention plays a critical role in all age groups. From a theoretic and practical perspective, however, greater emphasis should be placed on prevention in the earlier years because


the potential benefit is greater. As people age, chronic diseases develop, and a greater proportion of health care becomes dedicated to disease management. Because prevention is most beneficial in the younger years, one would expect that the preventive services provided to children are supported by a strong evidence base. On the contrary, there is a relatively large evidence base for determining beneficial preventive services for adults, but aside from immunizations, the evidence base for childhood services is generally much more limited (Moyer and Butler, 2004). Reasons for this lack of evidence base include length of follow-up required to realize reduction in disease outcomes, historical adoption and therefore standardization of many childhood preventive services, ethical considerations of not offering a potentially beneficial preventive service to children, methodologic challenges in determining developmentally appropriate outcomes in children, and the paradigm that knowledge alone represents a beneficial health outcome for families. These evidence gaps in prevention highlight the challenge of child research rather than invalidate the importance of prevention in children. The message must be made clear to physicians, parents, and children—prevention is important at all ages. Several categories of preventive services are relevant to children: immunizations, counseling and anticipatory guidance, screening tests, and preventive medications. Chapters 22, 23, and 24 discuss care for children, including preventive services.

Immunizations Immunizations, or vaccinations, usually are injections (oral in the case of the oral polio vaccine) that, when administered to an individual, elicit an immune response that protects the individual against the pathogen when future exposure occurs. Childhood is a particularly important time for immunizations because young children are still naïve to many viruses and bacteria, presenting an opportunity for primary prevention of disease. The CDC National Immunization Program has an Advisory Committee on Immunization Practices (ACIP) that meets regularly and annually releases a Childhood and Adolescent Immunization Schedule (www.cdc.gov/vaccines/) (CDC, 2009). A catch-up schedule is available for children who have missed previous immunizations. The ACIP, AAP, and AAFP also release the annual Harmonized Childhood and Adolescent Immunization Schedule, which has been endorsed by the three organizations. Periodic preventive care visits by family physicians provide opportunities for administration of these immunizations.

development and to prevent injury or harm. Examples of anticipatory guidance include providing counseling to caregivers about various safety issues (e.g., use of infant and child car seats, bicycle helmets, water safety, poisoning prevention, childproofing the home), nutrition, appropriate dental care, and physical activity. Injury prevention is particularly important because unintentional injury is the leading cause of death for children and adolescents. In children 1 to 14 years old, the three leading causes of injury-related death are motor vehicle crashes, drowning, and fire. Bright Futures (http://brightfutures.aap.org/web) is a wellknown, frequently implemented example of a program that includes health supervision and anticipatory guidance dedicated to well-child care and prevention. The Bright Futures program was begun by the Maternal and Child Health Bureau (MCHB) of the federal government and is endorsed by the AAFP and AAP. Preventive care of adolescents emphasizes anticipatory guidance and counseling. Important topics to discuss include sexual activity; alcohol, tobacco, and drug use; healthy eating and physical activity; injury prevention; and mental health. The evidence of the benefits of screening and counseling for these conditions in adolescence is not clear. The clinician must also ensure that immunizations are delivered to the adolescent according to the recommended schedule. Vaccination against hepatitis B should be administered if it was not given during infancy, and boosters for varicella; measles, mumps, rubella (MMR); tetanus, diphtheria, and pertussis are given as determined by the schedule. Adolescents, especially college students, are at increased risk for meningococcal meningitis. The risks of disease and the risks and benefits of immunization should be discussed with prospective college students. Screening tests for infants and children are discussed online at www.expertconsult.com.

Preventive Medications Preventive medications provide primary prevention of disease to average-risk or high-risk children. Preventive medications in childhood include fluoride for children with inadequately fluoridated drinking water and iron supplementation between ages 6 and 12 months for infants at high risk for iron deficiency anemia. Some preventive medications may be used in children with chronic diseases to prevent disease symptoms, progression, or complications; however, these medications may be considered disease management (i.e., tertiary prevention) rather than primary or secondary prevention.

Counseling and Anticipatory Guidance

Preventive Services for Pregnant Women

Anticipatory guidance appropriately targeted to a child’s developmental stage is a critical component of preventive care. Also, although good-quality evidence supporting the efficacy of most anticipatory guidance is limited, the standard of care is to provide such advice and counseling for parents (Moyer and Butler, 2004). Anticipatory guidance involves counseling caregivers to prepare for future normal child growth and development and to prepare caregivers for how these changes may need to be accommodated to promote

Preconception counseling and prenatal care largely focus on strategies to prevent or detect potential complications for the pregnant woman, fetus, and newborn. Routine preconception counseling may include risk assessment based on family history, counseling about use of folic acid for the prevention of neural tube defects, and counseling about the harms of smoking, alcohol use, and certain foods (e.g., fish with high levels of mercury) and drugs (prescription and illicit) on pregnancy outcomes. 91

6


Prenatal care includes screening tests, counseling, preventive medications, and immunizations. Screening laboratory tests include a complete blood cell count, blood type, Rh sensitivity, urinalysis for bacteriuria, screening for several STIs (e.g., syphilis, HIV, hepatitis B, gonorrhea [high risk], Chlamydia [high risk]), screening for neural tube defects, gestational diabetes mellitus, and group B streptococci (Kirkham et al., 2005). Counseling is often anticipatory guidance for the upcoming stages of pregnancy, delivery, and the postpartum period. Counseling for breastfeeding is a key preventive component to prenatal care, as is the use of prenatal vitamins and influenza vaccine administration. Chapter 21 discusses care of the pregnant patient, including prenatal preventive services.

Preventive Services for Older Adults An emphasis on a shared decision-making approach is especially important when considering preventive services for older adults. Family physicians and their older patients should consider issues that contribute to the complexity of prevention in older adults, including unique goals of prevention, life expectancy, comorbidities, potential for harm, and patient values and preferences (Harris et al., 2001). The patient’s values and preferences are always important, and shared decision making should occur before the preventive service is provided. Preventive aspirin therapy in elderly persons provides an illustrative example of the need for shared decision making. There are few studies on the use of aspirin for the prevention of cardiovascular disease in older adults. Older adults are at especially high risk of cardiovascular disease but also at high risk of gastrointestinal bleeding from aspirin. Some older men may decide that avoiding a myocardial infarction is of great value, and that having a gastrointestinal bleeding event is not a major problem, and they would probably decide to take aspirin (USPSTF, 2009). Specific preventive services that are of special interest for older adults include immunizations. The CDC recommends the zoster vaccine for all adults over age 60, pneumococcal vaccine for adults over 65, and influenza vaccine annually for adults over 50 (ACIP, 2009). Other preventive interventions of special importance target common causes of disease and disability and include multifactorial interventions for older adults that improve physical function, maintain independent living, and reduce falls (AGS, 2001; Beswick et al., 2008; Gillespie et al., 2006).

Counseling Although the leading causes of death in the United States remain heart disease, cancer, and cerebrovascular disease (stroke), in their landmark paper Actual Causes of Death in the United States, McGinnis and Foege (1993) concluded that 50% of U.S. mortality is caused by 10 lifestyle-related behaviors, including tobacco use, poor dietary habits, lack of physical activity, alcohol misuse, illicit drug use, and risky sexual practices. In a 2004 update, Mokdad and colleagues found that more than one third of U.S. mortality in 2000 was linked to four behaviors: tobacco use, alcohol consumption, poor diet, and physical inactivity. Changing the health behaviors of Americans has the greatest potential impact of 92

any current approach for decreasing morbidity and mortality and for improving the quality of life across diverse populations (Whitlock et al., 2002). A growing body of evidence demonstrates that brief interventions integrated into routine primary care can effectively address the most common and important health risk behaviors encountered in family medicine, including smoking cessation, healthy diet, regular physical activity, appropriate alcohol use, and responsible use of contraceptives. Simple, direct, and brief advice from the physician to change lifestyle habits has been shown to be effective in encouraging smoking cessation, reducing problem drinking, and modifying some cardiovascular risk factors associated with activity and diet (Whitlock et al., 2002). If 60% to 90% of practicing physicians regularly advised patients not to smoke, an additional 63,000 smokers would quit each year (Hollis, 2000). This approach works, and patients expect and want it. More than 95% of adults report that they expect their physicians to give them information about health behaviors and assistance in changing negative ones (Vogt et al., 1998). Not surprisingly, clinician advice has been associated with increased satisfaction with medical care. Behavioral counseling interventions have expanded beyond the limits of one-on-one interactions between physicians and patients. Physicians’ efforts are enhanced when the entire health care team takes appropriate and complementary roles in delivering interventions. For example, many components of successful interventions can take place outside the traditional physician-patient encounter. The patient can complete a health risk assessment while waiting to see the doctor; a trained staff member can do in-office counseling after the clinical encounter; a patient may be referred to a community-based program; and a follow-up visit or telephone call may be arranged. To emphasize the potential impact of a team approach, if a health care team member provides an additional 10 minutes of targeted assistance to one half of the patients who received brief advice on smoking cessation from the physician, the number of people expected to quit increases from 63,000 to 630,000 (Hollis, 2000). The use of additional resources, however, does not lessen the central importance of the clinician-patient relationship in promoting behavioral change. Effective clinician communication is essential in promoting behavior change. Appreciating the impact of behavioral change interventions requires a broad population-based perspective. A family physician may become discouraged if only 5% to 14% of those receiving an intervention make clinically significant changes, such as quitting smoking. However, even modest effects result in tremendous benefits to the community when systematically applied to the large number of those in need. The potential for substantial public health benefit from office-based behavioral change interventions will be realized only when these interventions are applied broadly and regularly (see Chapter 7).

The “5As” Framework In 2000, building on earlier work from the U.S. National Cancer Institute, the CTFPHC proposed a framework to guide physicians and health care systems in organizing their general approach to assisting patients with behavioral counseling interventions. In 2002, USPSTF adopted the


Table 6-6 The Five “A” Components of Behavior Counseling Interventions Assess: Ask about or assess behavioral health risks and factors affecting choice of behavior change goals or methods. Advise: Give clear, specific, and personalized behavior change advice, including information about personal health harms and benefits. Agree: Collaboratively select appropriate treatment goals and methods based on the patient’s interest in and willingness to change the behavior. Assist: Using behavior change techniques, aid the patient in achieving agreed-on goals by acquiring the skills, confidence, and social or environmental supports for behavior change, supplemented with adjunctive medical treatments when appropriate (e.g., pharmacotherapy for tobacco dependence, contraceptive drugs or devices). Arrange: Schedule follow-up contacts (in person or by telephone) to provide ongoing assistance or support and to adjust the treatment plan as needed, including referral to more intensive or specialized treatment. Intervention to help patients change unhealthy behaviors often requires repetition over time. Modified from Whitlock EP, Orleans CT, Pender N, Allan J. Evaluating primary care behavioral counseling interventions: an evidence-based approach. Am J Prev Med 2002;22:267-284.

f ramework, known as the “5As,” for evaluating the effectiveness of behavior counseling interventions (Table 6-6). The 5As framework is a powerful tool that can assist physicians in developing and evaluating their practice’s behavior change interventions. USPSTF offers guidance on the evidence base for behavior change interventions for many specific behaviors.

Assessing Behavior Systematic routine behavior risk factor assessment is the foundation for proactive behavioral counseling interventions and identifies all those in need of assistance. For example, having a system in place to identify and document tobacco use triples the odds of clinician intervention (Fiore et al., 2008). Assessment tools should be brief, easy to complete, and easily scored or interpreted. Assessment may range from a single focused question asked as part of taking the vital signs (e.g., Have you used tobacco products at all in the past 7 days?) to comprehensive tools known as health risk appraisals (HRAs). HRAs may be mailed or e-mailed to patients in advance of their appointments. Some are available for completion or scoring by computer; others are available on the Internet (e.g., HowsYourHealth.org, MyHealthyLiving.net).

physician, I feel I should tell you that . . . ,” the physician conveys respect for and avoids undermining patient autonomy (Whitlock et al., 2002). Placing confidence in the patient’s ability to change and acknowledging past successes build patient’s self-efficacy. Advice messages should not be lectures and should be delivered in 30 to 60 seconds.

Agreeing with the Patient Only when the patient and physician agree that change is desired should goals and options be explored. Assessing the patient’s motivation to change may be useful at this point, because appropriate interventions for those who are ready to change and for those who are not are likely to differ. For people with multiple behavioral risks, agreement is needed about which behavior change to focus on first. Physicians should partner with patients in considering the potential interventions. When patients are actively involved in making health care decisions, their choices are based on realistic expectations and are aligned with their own values.

Additional Assistance Additional assistance within or outside the patient visit is likely to produce better outcomes than advice-only treatment. Busy clinicians, however, often do not have time to provide more than brief counseling (1-3 minutes). Behavior change interventions should incorporate additional team members and linkage to community resources. Many health systems use dieticians, nurse care managers, social workers, and trained medical assistants to provide assistance to patients as part of behavior change interventions. Assistance may take the form of additional behavior-specific counseling, general patient motivation and activation, or referral to a community resource. In addition to traditional print materials, interactive computer and web-based programs that assist behavior change are becoming available.

Arranging Follow-up Behavior change requires follow-up. The physician may simply inform the patient of plans to follow up at their next regularly scheduled visit, making a note in the chart. Usually, however, initial follow-up should be scheduled within a relatively short period. Depending on the change being undertaken, follow-up may consist of a phone call a few days after a scheduled quit date, an e-mail inquiring about progress, or an in-office visit. After the initial follow-up, future contacts may often be spaced at successively longer intervals.

Theories and Models of Behavior Change Advising the Patient Physicians are influential catalysts for patient behavior change. By providing explicit health behavior advice, physicians establish that lifestyle changes are an important part of health care and motivate patients to change. Advice is most powerful when personalized and linked to a patient’s own concerns, experiences, or values. A warm, empathetic, and nonjudgmental style engenders cooperation and less resistance. By qualifying advice with remarks such as, “As your

Behavior change theories and models can help physicians conceptualize the complex context in which individual behavior change occurs and the variability among patients’ acceptance of behavior counseling interventions (Table 6-7). Insights gained from applying the models may help clinicians clarify barriers and opportunities when working with a given individual and customize an intervention based on an individual’s needs, such as determining which patients may respond best to a more intensive intervention. 93

6


Table 6-7 Theories and Models of Individual Behavior Change

Theory or Model

Focus

Key Concepts

Health belief model

Peoples’ perceptions of the threat of a health problem and appraisal of the behavior recommended to prevent or manage the problem.

Perceived susceptibility Perceived severity Perceived benefits of action Perceived barriers to action Cues to action Self-efficacy

Theory of reasoned action, theory of planned behavior

People are rational beings whose intention to perform a behavior is strongly related to its actual performance through beliefs, attitudes, subjective norms, and perceived behavioral control.

Behavioral intention Subjective norms Attitudes Perceived behavioral control

Stages of change, transtheoretical model

Readiness to change or attempt to change a health behavior varies among individuals and within an individual over time. Relapse is a common occurrence and part of the normal process of change.

Precontemplation Contemplation Preparation Action Maintenance Relapse

Behavior is explained by dynamic interaction among personal factors, environmental influences, and behavior.

Observational learning Reciprocal determinism Outcome expectancy Behavioral capacity Self-efficacy Reinforcement

Social cognitive theory, social learning theory

Modified from Whitlock EP, Orleans CT, Pender N, Allan J. Evaluating primary care behavioral counseling interventions: an evidence-based approach. Am J Prev Med 2002;22:267-284.

Most behavior change theories focus on the diverse, interacting levels of influence on an individual’s behavior. For example, the stages of change (transtheoretical) model emphasizes that change is an ongoing process with multiple stages that often include relapse and recycling into new efforts to change. The concept of self-efficacy stresses that individual behavioral change requires the belief that change is needed and possible. Many theories recognize the dynamic interaction between intrapersonal, interpersonal, and environmental issues, including factors such as age, race, ethnicity, and socioeconomic status.

Systems Change Family Physicians within the Health Care System Family physicians are responsible for providing care for acute illnesses and chronic conditions. They also provide preventive services, including screening, immunizations, and 94

behavioral counseling. In the disease-based model of health care, preventive care is often viewed as a competing demand. Americans, however, made more than 480 million visits in 2002 to their primary care physicians. As a trusted and wellused source of information and care, the family physician has a tremendous opportunity to improve the health of individual patients and entire communities through the provision of preventive services. The good news is that family physicians, despite limited face-to-face time with patients, already spend a significant amount of time promoting health behaviors. One large study found that physicians addressed health behaviors during one half of all visits, spending on average more than 10% of the visit promoting health (Stange et al., 2002). Further improvements in the provision of preventive services require more than improving clinician knowledge and attitude. Improving the quality, delivery, and effectiveness of prevention in primary care office practice requires changes in the office system. The family physician and other primary care clinicians must be integrated into a larger health care delivery team.

Using the 5As Model in a System Of the five steps in the 5As model (assess, advise, agree, assist, and arrange), the family physician is likely to be most effective when charged with focusing on the advise and agree steps. The staff member who triages the patient may be assigned the responsibility of administering a brief health risk assessment or reviewing a flow sheet of preventive services and noting on the chart if the patient is due for an immunization or screening test. During the visit, the prompted physician can advise the patient to be more physically active and explore the patient’s motivation to change or recommend a flu shot or cholesterol test. Most importantly, other members of the health care team can assist patients in learning additional information, acquiring new skills, choosing between options, and creating a personalized action plan. Team members, including nurses, medical assistants, social workers, and care managers, can link patients to resources in the community to support health behavior change and arrange follow-up (see Chapter 2).

The Chronic Care Model The chronic care model (CCM) has been proposed as a useful framework for considering the system changes necessary to construct a health care system that proactively promotes healthy behaviors and trains clinician and patients to work as partners in a collaborative care process (Glasgow et al., 2001) (Figure 6-3). The CCM identifies six essential elements of a health care system that together foster interactions between an informed, activated patient and a prepared, proactive health care team. The model defines six broad dimensions that must be considered when redesigning systems of care: organization of care, clinical information systems, delivery-system design, decision support, selfmanagement support, and community resources (Wagner, 1998). As a model, the CCM does not provide a specific set of interventions; instead, it acts as a framework within

Preventive Health Care CHRONIC CARE MODEL

Community

Health system

Resources and policies

Health care organization Selfmanagement support

Delivery system design

Informed, activated patient

Productive interactions

Decision support

Clinical information systems

Prepared, proactive practice team

Outcomes Improved outcomes Figure 6-3 The chronic care model. (Modified from Wagner EH. Chronic disease management: what will it take to improve chronic illness? Effect Clin Pract 1998;1:2-4.)

which improvement strategies can be tailored to local conditions. In an individual office, the application of the CCM toward improving the quality of preventive services may lead to any of the following: • Developing a patient registry for child and adult immunizations (i.e., clinical information system). I • mplementing standing orders that all patients with diabetes receive a home glucose monitor and meet with a nurse educator (i.e., delivery system design). • Referring all prenatal patients to a local La Leche League meeting (i.e., community resources). • Designing a prompt to cue physicians to schedule a mammogram (i.e., decision support). • Integrating achievement of prevention goals into physician performance bonuses (i.e., health system organization). • Training physicians to use the techniques of motivational interviewing to set goals in collaboration with patients and identify personal barriers and supports after advising smokers to quit (i.e., self-management support).

Rethinking the Periodic Health Examination Although the periodic health examination means many things to many people, most agree that it refers to a patient encounter focusing on health maintenance and disease prevention. Exactly which preventive services should be offered during such a periodic examination varies in practice; however, the services discussed in this chapter have been shown to improve patient-oriented health outcomes. Many of these services may be provided during regular office visits and in the context of a periodic health maintenance visit. Batteries

of tests (e.g., screening laboratory tests, ECGs) and general head-to-toe physical examinations often performed during preventive periodic health examinations (e.g., heart and lung auscultation, abdominal palpation) are not effective as general screening strategies in the general population. Instead, a customized preventive service package is most useful.

Conclusions Preventive services should be tailored according to the individual patient’s risk factors, preferences, and comorbid diseases. Although no “one size fits all” prevention plan can work for everyone, the following tenets remain true: 1. Prevention can lead to major health benefits, but all prevention attempts are not necessarily beneficial, and some services may be harmful. 2. Evidence for preventive service effectiveness can be used to prioritize preventive services for averagerisk and high-risk patients in a family physician’s practice. 3. Systems approaches using team models for provision of services, reminder systems, and electronic health records are critical to improving the use of evidence-based preventive services. 4. Counseling is a key component in prevention and requires health professionals trained in counseling modalities. Providing evidence-based preventive services, including immunizations, screening tests, and behavior change interventions, is possible with planning, teamwork, and practice redesign. 95

6


EVIDENCE-BASED SUMMARY The U.S. Preventive Services Task Force (USPSTF) grades its recommendations according to one of five classifications (A, B, C, D, I), reflecting the strength of evidence and magnitude of net benefit (benefits minus harms):

GRADE

DEFINITION

SUGGESTIONS FOR PRACTICE

A

USPSTF recommends the service. There is high certainty that the net benefit is substantial.

Offer or provide this service.

B

USPSTF recommends the service. There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial.

Offer or provide this service.

C

USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.

Offer or provide this service only if other considerations support the offering or providing the service in an individual patient.

D

USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.

Discourage the use of this service.

I Statement

USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

Read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.

From U.S. Preventive Services Task Force Table of Recommended Preventive Services for 2001 to April 2009.

USPSTF CATEGORY A AND B RECOMMENDATIONS SERVICE

POPULATION

COMMENTS

Screening for abdominal aortic aneurysm

Ever-smoking men ages 65-75 years: B

Never-smoking men ages 65-75: C Women: D

Screening for alcohol misuse

Adults: B

Adolescents: I

Aspirin for primary prevention of cardiovascular events

Men age 45-79 to prevent myocardial infarction (MI): A Women age 55-79 to prevent stroke: A

Men younger than 45 to prevent MI: D Women younger than 55 to prevent stroke: D Men and women 80+ to prevent cardiovascular disease: I

Screening for asymptomatic bacteriuria

Pregnant women: A

Nonpregnant women and men: D

Discussion of chemoprevention of breast cancer

Women at increased risk of breast cancer and decreased risk of adverse events: B

Women not at increased risk of breast cancer: D

Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility

Women whose family history is associated with increased risk for deleterious mutations in BRCA1 or BRCA2 genes: B

Women whose family history is not associated with increased risk for deleterious mutations in BRCA1 or BRCA2 gene: D

Screening for breast cancer with mammography

Women age 50+: B

Women 40-49: C Screening with clinical breast exam: I Breast self-exam: D

Counseling to promote breastfeeding

Interventions during pregnancy and after birth to promote and support breastfeeding: B

No subgroups

Screening for cervical cancer with Pap smear

Women younger than age 65 who are sexually active and have a cervix: A

Women over 65 who have had previous negative screens: D Women who have had total hysterectomy for benign disease: D Screening with new technologies: I Screening with HPV: I

Screening for Chlamydia

Sexually active nonpregnant women ≤24 and older nonpregnant women who are at increased risk: A

Pregnant women ≤24 and older pregnant women who are at increased risk: B Women ≥25 and older, whether or not they are pregnant, if they are not at increased risk: C Men: I

Pregnant women 6 years old: B

Screening with low- to moderate-intensity counseling: I Counseling for overweight, not obese: I

Screening for osteoporosis

Women age 65+ and younger women with risk factors: B

Men: I

Screening for phenylketonuria in newborns

Newborns: A

No subgroups

Behavioral counseling to prevent sexually transmitted infections (STIs)

Sexually active adolescents and adults at increased risk for STIs: B

Non–sexually active adolescents and adults not at increased risk: I

Screening for sickle cell disease

Newborns: A

No subgroups

Screening for syphilis in pregnant women

All pregnant women and all persons at risk: A

All persons not at risk: D

Screen for tobacco use and provide tobacco cessation interventions

Adults: A Pregnant women: A

Screening for tobacco use or interventions to prevent or treat tobacco use among adolescents and children: I

Visual impairment to detect amblyopia, strabismus, visual field defect

Children younger than 5 years old: B

No subgroups

HPV, Human papillomavirus; CVD, Cardiovascular disease.

97

6


USPSTF CATEGORY D RECOMMENDATIONS: PREVENTIVE SERVICES NOT RECOMMENDED IN GENERAL POPULATION SERVICE

POPULATION

COMMENTS

Screening for abdominal aortic aneurysm

Women: D

Ever-smoking men age 65-75: B Never-smoking men age 65-75: C

Aspirin for primary prevention of cardiovascular events

Men younger than 45 to prevent myocardial infarction (MI): D Women younger than 55 to prevent stroke: D

Men age 45-79 to prevent MI: A Women age 55-79 to prevent stroke: A Men and women 80+ to prevent cardiovascular disease: I

Aspirin/NSAIDs to prevent colorectal cancer

Adults at average risk: D

No subgroups

Screening for bacterial vaginosis

Pregnant women at low risk for preterm delivery: D

Pregnant women at high risk for preterm delivery: I

Screening for asymptomatic bacteriuria

Men and nonpregnant women: D

Pregnant women: A

Beta-carotene supplements

Adults: D

Supplemental vitamins A, C, and E or folic acid or antioxidant combinations: I

Screening for bladder cancer

Adults: D

No subgroups

Screening for breast cancer

Women breast self-exam: D

No subgroups

BRCA mutation testing for breast and ovarian cancer susceptibility

Women whose family history is not associated with increased risk for deleterious mutations in BRCA1 and BRCA2: D

Women whose family history is associated with increased risk for deleterious mutations in BRCA1 and BRCA2: B

Carotid artery stenosis

Adults: D

No subgroups

Chemoprevention of breast cancer

Women not at increased risk of breast cancer: D

Women at increased risk of breast cancer and decreased risk of adverse events: B

Chemoprevention for hormone replacement therapy

Postmenopausal women: D Postmenopausal women who have had a hysterectomy: D

No subgroups

Screening for chronic obstructive pulmonary disease

Adults: D

No subgroups

Cervical cancer screening with Pap smear

Women over 65 who have had previous negative screens Women who have had total hysterectomy for benign disease: D

Women under 65 who are sexually active and have a cervix: A Screening with new technologies: I Screening with HPV: I

Screening for coronary heart disease (CHD)

Adults not at increased risk, using ECG, ETT, or EBCT: D

Adults at increased risk: I

Screening for colorectal cancer

Adults 85+: D

Adults 50-75: A Adults 76-85: C Computed tomography colonography and fecal DNA testing as screening modalities for colorectal cancer: I

Screening for genital herpes

Asymptomatic pregnant women: D Asymptomatic adolescents and adults: D

No subgroups

Screening for gonorrhea

Men and women at low risk: D

Sexually active women, including those who are pregnant if they are at high risk : B Newborns: A Men at high risk and pregnant women at low risk: I

Screening for hemochromatosis

Asymptomatic general population: D

No subgroups

Screening for hepatitis B infection

General population: D

Pregnant women: A

Screening for hepatitis C

Not at increased risk: D

Increased risk: I

Screening for idiopathic scoliosis

Adolescents: D

No subgroups

Screening for lead in childhood and pregnancy

Children age 1-5 years who are at average risk: D Pregnant women: D

Children age 1-5 years who are at increased risk: I

Screening for ovarian cancer

Women: D

No subgroups

Screening for peripheral arterial disease

General population: D

No subgroups

98


SERVICE

POPULATION

COMMENTS

Screening for prostate cancer

Men >75: D

Men 50 years

Breast cancer: 16% reduction after 20 mammograms

0

Prostate-specific antigen (PSA) testing DRE

Prostate cancer: 0% reduction after 25 PSA tests

0

DRE, breast self-examination (BSE), physical examination

0% reduction after 40 years

0

Statins (AFCAPS/TexCAPS Study)‡

37% reduction in combined myocardial infarction, unstable angina, and stroke

0

Eight major lifestyle studies (see Tables 7-3 and 7-4): chronic disease and death

35%-83% reductions in coronary events 50%-71% reduction in stroke events 58%-93% reduction in onset of diabetes 36%-68% reduction in cancer deaths

40%-65%

4S Simvastatin Study§

34% reduction in major coronary events 42% reduction in coronary mortality in patients with heart disease

30%

West of Scotland Coronary Prevention Study (WOSCOPS)⁋

Statins reduced coronary events by 31% and cardiovascular specific mortality by 32%.

0

The MRC/BHF Heart Protection Study¶

25% reduction in first-event rate for nonfatal myocardial infarction or coronary death, fatal or nonfatal stroke, and for coronary revascularization with 40-mg simvastatin in high-risk patients over 5 years in 20,536 U.K. adults age 40-80 years

12.9%

Beta blockers after myocardial infarction#

27% reduction of nonfatal infarction in 25 randomized trials (>23,000 patients)

22%

Intervention Primary Prevention

Secondary Prevention

*All data from current U.S. Preventive Services Task Force (USPSTF) appraisal of the evidence and recommendations. http://www.ahrq.gov/clinic/uspstf08/colocancer/colors.htm#r ationale; http://www.ahrq.gov/clinic/3rduspstf/cervcan/cervcanrr.htm; http://www.ahrq.gov/clinic/3rduspstf/breastcancer/brcanrr.htm; http://www.ahrq.gov/clinic/uspstf08/pro state/prostaters.htm. †Black WC, Haggstrom DA, Welch HG. All-cause mortality in randomized trials of cancer screening. J Natl Cancer Inst 2002;94:167-173. ‡Downs JR et al., for AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998;279:1615-1622. §Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S Study). Lancet 1994;344:1383-1389. ⁋Shepherd J et al., for West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1994. ¶Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebocontrolled trial. Lancet 2002;360:7-22 #Yusuf S, Wittes J, Friedman L. Overview of results of randomized clinical trials in heart disease. I. Treatments following myocardial infarction. JAMA 1988;260:2088-2093.

endorsed explicit global cardiac risk assessment as the new standard of care:

Most current guidelines focus primarily on the management of individual cardiovascular risk factors, such as high blood pressure, hypercholesterolemia, or diabetes. A more appropriate clinical approach to reducing cardiovascular disease risk would be based on a comprehensive evaluation of risk profile, and 102

accurate stratification of global (absolute) risk in individual patients. . . . The decision to treat a patient should be based on the level of global risk, rather than on the level of a single risk factor. . . . We proposed that global risk should be used as the main determination of whom to treat, how to treat, and how much to treat. . . . We propose to replace the single risk factor–based approach with the assessment of global

Lifestyle Interventions and Behavior Change

cardiovascular risk, both in the clinical management of individual patients and in guidelines. (Volpe et al., 2004) Once the importance of carrying out some form of global cardiac risk assessment is accepted, a physician need only choose a method and use it consistently. A basic quality-ofcare goal process standard would be to use the method of CAD risk assessment systematically for at least 85% of all adult patients over 85% of all years. There are many ways to carry out cardiac risk assessment—from the Framingham tables and equation (United States), by means of the NCEP ATP III risk calculator, to the Sheffield tables and the most recent technique, the QRISK calculator (United Kingdom) (Hippisley-Cox et al., 2008; Wallis et al., 1995). Many of these have been adapted for smart phones and personal digital assistants (PDAs) and are downloadable for free, so few major barriers to implementation exist, primarily time. A time-efficient method that can be used in the office setting includes a preprinted list of the 10 major cardiac risk factors supported by the current literature. Consider making a list that can be incorporated into the patient’s medical record, including the following: • Age >55 (males); >65 (females) • Male gender • Family history of CAD • Smoking • Hypertension • Diabetes • Sedentary lifestyle • Metabolic syndrome • High cholesterol level • Chronic renal insufficiency Other considerations include major adverse life event and high perceived stress at work or home. The purpose of this list is to classify all adults into one of three levels of risk: low, intermediate, or high. Where the dividing lines are drawn between categories is not as important as being consistent. In my practice, I consider up to three risk factors to be low risk, four to six factors to be intermediate risk, and more than six, high risk. This information (e.g., CAD Risk Score: “intermediate risk”) should go directly into the problem list so that the physician can see it each visit. The intervention itself is relatively inexpensive, requiring only 1 to 2 minutes of physician (or better, medical assistant) time and involving simple laboratory tests—lipid panel and serum creatinine. I define the “metabolic syndrome” as a triglyceride level greater than 150 mg/dL and high-density lipoprotein (HDL) level less than 40 mg/dL for men (or 24

150

NCEP Step 1 diet

—

Healthy Aging: A Longitudinal Study in Europe (HALE Project) (2004)

2339

70-95

10

Never, or quit >15 years

--—

200‡

Mediterranean Diet Score = 8§

Alcohol: >0 glass/day

Women’s Health Study (2006)

37,636

>45

10

Never

35

Never/rare 4 x/wk

Composite ⁋

Alcohol: 10.5

Health Professionals Follow-up (2006)

42,847

40-75 in 1986

16

Not currently

150

5 servings of fruits and vegetables daily

Alcohol: 1-14 units/ wk

EPIC-Norfolk (2008)

20,244

45-79

11

Not currently

---—

210

Vitamin C level >50 mmol/L#

Alcohol: 1-14 units

EPIC-Potsdam (2009)

23,153

35-65

7.8

Never

25, BMI >24, and either fasting blood glucose or post–75-g glucose load; 2-hour postprandial glucose elevated but not diagnostic for diabetes. ‡Individuals with a score in the intermediate and the highest tertile on the Voorrips or Morris questionnaire were considered the low-risk group for physical activity. §For the Mediterranean Diet Score, the subject must have had above-average consumption of the six positive variables: (1) polyunsaturated/saturated fatty acid ratio, (2) fruits, (3) vegetables, (4) legumes, (5) fish, and (6) grains. They also must have had below-average consumption of the two adverse factors: (7) red meat and (8) dairy products. ⁋Considered six dietary factors: cereal fiber, folate, polyunsaturated/saturated fat ratio, omea-3 fatty acids, trans fats, and glycemic load, grouped into deciles and scored as 0 to 9. ¶Calculated a summary dietary score based on the Alternate Healthy Eating Index (AHEI). #As a proxy for 5 servings of fruits and vegetables per day. **A healthy diet was considered to consist of high intake of fruits and vegetables, whole-grain bread, and low consumption of meat. NCEP, National Cholesterol Education Program; EPIC, European Prospective Investigation into Cancer and Nutrition. †Subjects

intima-media thickness), angina, left ventricular hypertrophy, and overall mortality. A review of controlled trials using Transcendental Meditation (TM) techniques (many of which also compared TM to progressive muscle relaxation and other stress reduction techniques) found the following (Walton et al., 2004): • Significant blood pressure reductions (11 mm Hg systolic and 6 mm Hg for diastolic) among elderly blacks (Alexander et al., 1996a; Schneider et al., 1995). • A 13% reduction in cigarette use and smaller but significant reductions in drug and alcohol use (Alexander et al., 1994). • Significant reductions in cholesterol after 11 months (Cooper and Aygen, 1979). • A 30% reduction in psychosocial stress (Eppley et al., 1989). • Implied reductions in atherosclerosis in patients with two or more risk factors for coronary heart disease of 33% after 1 year (Alexander et al., 1994, 1996a; Fields et al., 2002). 106

•

eduction in the likelihood of heart attack or stroke of R 11% among elderly blacks (Alexander et al., 1994, 1996a). • Greater exercise tolerance, maximal workload, delayed onset of ST-segment depression after 8 months (Zamarra et al., 1996). • A highly significant reduction in all-cause mortality (Alexander et al., 1989, 1996b). These studies are generally older, small in size, and of relatively poor methodologic quality (University of Alberta, 2007). However, these findings are supported by the INTERHEART study, which identifies psychosocial stress as one of the nine leading risk factors for MI (Rosengren et al., 2004; Yusuf et al., 2004). A relaxation or stress reduction variable is added to the basic lifestyle formula for two main reasons: (1) the mounting support from clinical research and (2) the epidemiologically well-established correlation of stress to overall morbidity and mortality (Figueredo, 2009). Also, a compelling commonsense belief among the general public holds that stress is bad for health and can be reduced by various behaviors.


Table 7-4 Outcomes of the Eight Major Prospective Lifestyle Studies

Study

Healthy Lifestyle at Baseline*

Nurses’ Health Study (2000)

3%

83% reduction in coronary heart disease (CHD) events; follow-up study showed a 91% reduction in the risk of type 2 diabetes.

Lifestyle or Metformin for Prevention of Diabetes (2002)

—

58% reduction in diabetes compared to placebo; vs. 31% reduction with metformin and “standard” lifestyle intervention.

Healthy Aging: A Longitudinal Study in Europe (HALE Project) (2004)

—

65% reduction in all-cause mortality (all 4 points); 77% reduction in CHD; 67% reduction in all cardiovascular diseases; and 68% reduction in all cancers. The lack of any healthy lifestyle characteristics was associated with a population-attributable risk of 60% of all deaths, 64% of deaths from CHD, 61% from all cardiovascular diseases, and 60% from cancer.

Women’s Health Study (2006)

4.7%

55% reduction of total stroke, 71% reduction ischemic stroke, and 27% increase in hemorrhagic stroke.

Health Professionals’ Follow-up Study (2006)

—

87% reduction in men for CHD; 62% of coronary events might have been prevented with the five healthy lifestyle factors; in men taking medication for hypertension or hypercholesterolemia, 57% of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during followup, those who adopted two or more additional low-risk lifestyle factors had a 27% lower risk of CHD.

Atherosclerosis Risk Factors in Communities (ARIC) (2007)

8.5%

During 4 years of follow-up, total mortality and cardiovascular disease events were lower for new adopters (2.5% vs. 4.2%) and 11.7% vs. 16.5% compared to individuals who did not adopt a healthy lifestyle. New adopters had 40% lower all-cause mortality and 35% fewer cardiovascular events.

EPIC-Norfolk (2008)

—

Adjusted relative risks for all-cause mortality for men and women who had 3, 2, 1, and 0 risk factors compared to 4 healthy behaviors were 1.39, 1.95, 2.52, and 4.04, respectively. All 4 behaviors = 14 more years of life.

EPIC-Potsdam (2009)

9%

Subjects with all 4 factors at baseline had a 78% lower risk of developing a chronic disease: diabetes, 93% reduction; myocardial infarction, 81% reduction; stroke, 50% reduction; and cancer, 36% reduction.

Major Findings

*Prior data on the prevalence of healthy lifestyle characteristics among U.S. adults demonstrated that only 3% had all four healthy lifestyle factors: not smoking, 5 servings of fruits and vegetables a day, 150 minutes of exercise a week, and body mass index (BMI) of 18.5 to 25 kg/m2. (Reeves MJ, Rafferty AP. Healthy lifestyle characteristics among adults in the United States, 2000. Arch Intern Med 2005;165:854-857.)

Currently, the data do not precisely define the minimum time needed in meditation or relaxation to achieve health benefits; many studies use 15 to 20 minutes daily (Lane et al., 2007). A reasonable conjecture of the “minimal effective dose,” which follows the work of Depak Chopra (1993), is 10 minutes a day. Chopra believes that nothing more than 10 minutes of silence is required. Progressive increases in time will enhance the benefits, but a place to start is needed, as with the BMI criterion. Thus, the revised list of essential components for a healthy lifestyle is as follows: 1. Not smoking 2. Five (5) servings of fruits and vegetables daily 3. Ten (10) minutes of relaxation or meditation exercise daily 4. BMI less than 30 kg/m2 5. Exercise for at least 150 minutes per week

This can be conveniently expressed by the simple numeric mnemonic 0-5-10-30-150, as follows: 0

Cigarettes a day

5

Servings of fruits and vegetables a day

10

Minutes of relaxation or meditation daily

30

BMI less than 30

150

Minutes of exercise a week

This is a concise notation for a prescription of 0 cigarettes a day, 5 servings of fruits and vegetables every day, 10 minutes of relaxation or meditation daily, a BMI less than 30, and 150 minutes of exercise each week. For a behavioral lifestyle intervention to be practical and acceptable to most physicians, it should be brief, easily memorable, and simple to communicate to patients. 107

7


The nine studies clearly indicate that certain lifestyle characteristics are associated with important reductions in both chronic disease and death. Also, only 3% to 9% of typical populations meet the varying requirements of a healthy lifestyle; the relevant number for the U.S. population from the national Behavioral Risk Factor Surveillance System is 3% (BRFSS, 2002). There is a huge population of people who do not have a healthy lifestyle and whom physicians can help by facilitating their transition to a healthier lifestyle. Of the studies previously described, in many ways the ARIC Study and the Prospective Diabetes Group trial are arguably the most important. These studies show directly that subjects who previously had a suboptimal lifestyle up into middle age can experience proportional benefits in health outcomes by making changes in their behavior at that time. These studies do not, however, tell us that physicians can persuade patients to make corresponding changes in their behaviors.

After the Evidence: Motivational Interviewing Key Points The most promising technique of active listening to help patients change behavior is motivational interviewing. The three essential tools of motivational interviewing are: • A menu • An importance “ruler” • A confidence “ruler” Resistance is to be expected and provides the physician with the best opportunity to assist patients to work on what they need to do for themselves.

The previous studies are adequate to meet information objectives, but this alone is insufficient. To help patients make changes in their lives—and each of these lifestyle habits represents major behavior change—it is necessary to help them discover their own motivations to make changes and to help build confidence in their ability to undertake the task. Providing information is a physician behavior that is usually well supported in traditional medical education and training. The pitfall, however, is that most primary care physicians were trained to use this information as the basis for giving advice to patients. Experience confirms that simply giving advice usually is ineffective, and to the contrary, the usually unwelcome advice often heightens resistance to new behaviors. Physicians cannot provide the motivation for patients to undertake lifestyle change, so it is necessary to ask patients what they want to do. What are their reasons for continuing a lifestyle habit that they usually know is associated with some adverse effects on their health? All patients have such reasons, or the behavior would simply go away. Unhealthy lifestyles are perpetuated when internally the “pros” in favor of a given behavior have reached a stalemate with the “cons,” and a search for new behavior stops. The role of physicians is to help patients break the stalemate by creating opportunities for patients to reflect on their own behavior and values. A physician demonstrates respect for patients’ autonomy and their right to make decisions for themselves when, after an examination of the pros and cons, 108

the physician accepts wherever patients are with change in their life and allows them to guide the clinician to the areas where they are most motivated to change. The greatest problem is that family physicians were never trained to do this; it does not just happen. The way to make it happen is by listening. This is true regardless of which evidence physicians believe and what attitudes patients have. “Long before there was any scientific basis for health care, there were healers who had learned to listen carefully” (Rollnick et al., 2008, p. 65). The most promising new technique of “active listening” for health care practitioners is motivational interviewing (MI). It is beyond the scope of this chapter to provide detailed instructions in the related skills, which must be experienced and practiced over at least a few months. This section discusses the underlying principles and simple ways to start implementing these skills in medical practice. The development of skills requires sufficient understanding of the basic theory of MI to try the related clinical style with patients. Patients will then provide enough direct and immediate feedback to help physicians quickly refine their skills. The relevant basics of theory and practice are readily accessible (Rollnick et al., 1999, 2008; see also Web Resources). The clinical method of MI was first described in 1983 as an approach to problem drinking (Stockwell and Gregson, 1986). MI is a “skillful clinical style for eliciting from patients their own good motivations for making behavior changes in the interest of their health” (Rollnick et al., 2008, p. 6). MI is a collaborative partnership between patients and their physicians based on the assumption that motivation for behavioral change is “malleable” and is formed particularly in the context of relationships. In addition, MI requires of physicians a “certain detachment from outcomes—not an absence of caring, but rather an acceptance that people can and do make choices about the course of their lives” (Rollnick et al., 2008, p. 7). Rollnick identifies four core guiding principles of MI, using the mnemonic RULE, as follows: Resist the “righting reflex” (i.e., “Don’t try to fix it, and don’t give advice”). Understand the patient’s motivations. Listen; use empathic, active listening throughout the clinical interview. Empower the patient. The physician needs to support patients’ beliefs that change is possible and will make a profound difference in their life. The key change in physician behavior required is a transition from asking multiple, “get to the point,” close-ended questions, often mistakenly assumed to be efficient, to a style that employs fewer and predominantly open-ended questions. This allows patients the time to tell their stories. The benefit for patients is the feeling of being heard. For physicians, the benefit can be greater patient satisfaction; patients often feel they had more time with the physician and received more attention, whether or not the visits are actually longer. The challenge is to allow the patient to be in control. Another good example of a systematic approach to MI in the clinical setting is the Kaiser TPMG educational program. The Brief Negotiation Roadmap offers a practical six-step sequence for physicians in practice: (1) open the encounter; (2) negotiate the agenda; (3) assess readiness; (4) explore ambivalence; (5) tailor the transition; and (6) close the


encounter. The Kaiser example offers a good illustration of the use of the three basic tools of MI: a “menu” for the agenda, a motivational “ruler,” and a confidence “ruler.”

The Process in Your Clinical Practice The encounter for lifestyle change opens with the establishment of rapport and trust with your patient. You are assisting the patient to be in control of the encounter and trying to establish a partnership for what needs to be done, which only the patient can decide. Your role is to assess the patient’s level of healthy lifestyle activity, educational needs, emotional state, and readiness to embark on change, and to reflect these back to the patient as they become clear. A good way to open the discussion is to present a list of options (a “menu”) that you and the patient might work on together for the encounter. Ask if this is acceptable. You can identify a patient’s readiness for behavioral change simply by asking the patient about the positive aspects of the patient’s current behavior and then listening. Follow this up with a similar question, What are the negative aspects of this behavior? To assess the current state of the tension between the positive and negative aspects, using a motivational “ruler,” ask the patient how important it is to change the current behavior, on a scale of 1 to 10. If the patient rates the importance of change as only a 2 out of 10, you can ask, “Why isn’t it a zero or a one?” If it is a 6, you can ask, “What would it take to make it a seven?” The goal of this interaction is simply to understand the patient’s readiness for behavioral change and to facilitate the patient’s recognition of his or her own ambivalence. The uncovering of ambivalence is a useful step forward, not a failure on the physician’s part. Ambivalence must exist, or the behavior would have changed already. Ambivalence is the reason for the encounter. The physician must try to understand what creates the tension that results in ambivalence. Ambivalence can be addressed; a clear “no” cannot. If the patient turns out not to be ready for change, the patient is probably right. Only the patient fully understands all the competing values in his or her life. Acknowledge that directly, asking such questions as, “Where does that leave you now?” or “What are you thinking/feeling at this point?” If the patient is ready for change, you want to find out how much and how fast. Let the patient be in charge. A good question is, “How can I help?” If the patient does not have a specific task for you right now, you can always just offer information from a clinical perspective. Ask if this is acceptable. Try to reach mutual clarity about what to expect. “How confident are you that you can cut your smoking in half this week?” On a confidence scale (1-10), physicians are seeking a level of 7 out of 10, to indicate that the patient is really confident about making a change. If the answer is less than 7, you can gently suggest considering a lower goal. For example, “Well, if you only feel a confidence of 5 about cutting your smoking in half, how confident would you feel about reducing your smoking by two cigarettes a day this week?” When you have a firm degree of confidence (≥7) about a mutually agreed goal, you are ready to close the encounter. Affirm the effort the patient is making to enhance the quality of his or her health. Affirm that you will be there for the patient at each turn on this path to lifestyle change.

Basic Steps toward Self-Motivation 1. E licit agreement with the patient that it is acceptable to talk about behavior change for any issue. 2. Ask what the patient sees as positive aspects of his or her current behavior, then ask about the negative aspects. 3. Use the motivational RULE to assess how important it is now for the patient to make a change in the target behavior.” 4. Ask how confident the patient is about making a change. 5. Resolve ambivalence. Revise the degree of anticipated change in the target behavior until the patient’s confidence level is 7 or higher. If this is not possible, explicitly acknowledge that this may not be a good time to undertake change in this area. 6. Close the encounter with encouragement toward the patient’s stated goal or an offer to be of assistance whenever the patient is ready.

Crux of the Lifestyle Dilemma: Do Physicians Believe in Primary Prevention? Key Points • G ood, even great, evidence is not enough to lead to substantial lifestyle changes among patients. • Traditional medical training has not prepared the majority of practice physicians in the science (evidence) of primary prevention or in the tools necessary to make it happen, such as motivational interviewing. • Although many physicians say they believe in primary prevention, their behavior often belies this. Belief in the power and effectiveness of primary intervention strategies among primary care physicians cannot be assumed and must be explored individually with each physician. • Physicians need to go through a series of steps, much as any patient who desires to change a behavior, to become proficient at primary prevention. • The predicted results will reward the efforts for physicians who can take a day-by-day, long-term perspective on health.

Why not primary prevention now? Whether this means systematically performing CAD risk assessments on all adult patients, or whether the physician wants the broadest possible impact on multiple major chronic diseases through primary prevention, the rate-limiting step is the same: motivation. As with patients, too few physicians actively engage in either strategy. What would be required for lifestyle work to become a critical part of every patient encounter? Motivational interviewing theory suggests that the behavior is not important to physicians, or they lack skill in this technique. The data cited have now been long available. Physicians do not lack an evidence base to justify such a behavior change; they lack the will. They should examine this phenomenon as a perfect problem to approach with MI skills. The problem is usually couched in terms of patient compliance and patient resistance as the source of failure to adopt a healthy lifestyle. This may be true in part, but the physician also plays a role. The principles of MI, applied to patients, suggest that physicians need to understand patients’ perspective better and, whatever their resistance, why they do want to take care of 109

7


themselves (Rollinik et al., 2008; Ruback et al., 2005). One can never positively influence the behavior of another person without continuous, positive, empathic, nonjudgmental support. Another barrier in providing primary prevention is that no one has directly observed a primary prevention “miracle.” Although so important to the religious conversion experience, miracles just don’t happen in primary prevention. Prevention of poor outcomes is not an observable event. In usual practice, physicians derive the most satisfaction by testing or treating and seeing a prompt result. The relatively simple “instant gratification” of this approach is addictive. Give sublingual nifedipine, and the patient’s blood pressure decreases; give insulin, and the sugar level is reduced. Tap on a reflex, and the tendon jumps; order a CT scan, and unseen abnormalities become apparent. Primary prevention offers no such satisfaction, even though it may be a favorite subject of interest, with a gratifying sense of sharing a deep belief. Motivating physicians to move toward a primary prevention lifestyle and practice (these must go together) is similar to moving a smoker toward smoking cessation. All patients who are smokers should receive at every physician visit a straightforward, simple, clear, nonjudgmental message that giving up smoking is the single most important thing they could do for their health. This message should be accompanied by a simple question, “Would you like to talk about it?” Although average results from simple, brief counseling are 2.8% quit rates (Lancaster and Stead, 2004), because of the large patient populations, this rate is actually quite important. Physicians must be willing to accept intermediate behavioral outcomes in this range: 3% to 5% increases in smoking cessation (Butler et al., 1999), exercise (Hillsdon et al., 2007; Lawlor and Hanratty, 2001; Ogilvie et al., 2007; Peterson, 2007; Sherman et al., 2007), eating 5 servings of fruits and vegetables (Steptoe et al., 2003), other healthy nutrition practices (Hunt et al., 1995), reducing problem drinking (Fleming, 2005; Ockene et al., 1999), accident prevention (Miller and Galbraith, 1995), and general healthy lifestyle advice (Christian et al., 2008; Steptoe et al., 2001). Each physician should reflect on the following questions: 1. “Do I believe that primary prevention can really work, and that it can substantially outperform other strategies to promote health?” As noted, belief is required. Exposure to high-quality primary prevention information can help, especially with urging from a colleague or mentor. We cannot assume that physicians believe; we have to ask. Belief is a journey, and the physician must explore personal history and professional socialization, first asking, “On a scale of 1 to 10, how great is my belief that primary prevention is the right thing to do and the key to the best results in medicine?” 2. “If I do believe in primary prevention, do I think it is important?” The physician must be convinced that this is a worthwhile focus. The physician’s belief in the relative importance of preventive interventions is influenced by example, information, patient satisfaction, and organizational support. If primary prevention is not important, it does not deserve to be practiced. If the physician thinks it is even somewhat important, however, primary prevention warrants further consideration. 3. “If I believe in primary prevention, and I believe it is of paramount importance, am I convinced that I can do it?” Confidence is also relative and susceptible to both information and example. The physician needs to ask, 110

“On a scale of 1 to 10, how confident am I that I can integrate the behaviors necessary for primary prevention into my life and work flow?” The evidentiary basis, practice, and strategies of motivational interviewing are new enough that many physicians are not even familiar with the term. Many of these physicians, however, intuitively respond to the process and may think,— “I’ve done that; I just didn’t know what it was called.” Usually, however, MI is only targeted at patients with high-risk medical conditions. As a strategy, it has succeeded dramatically for certain patients, but MI has not penetrated far into the U.S. health care environment since it was introduced to a wide audience in 1992. MI simply is not a formal part of most practices, mainly because the power of the intervention has been aimed at the wrong strata of system participants. Insufficient data and insight surround the major question, “How do we nurture physicians in their career development to have firsthand knowledge of the power to change and evolve personally?” If the United States is to become a healthier country, current health care reform policies should address this question directly. Primary prevention can then become a natural, integral part of the health care process, an act as simple as breathing.

Summary The answers to the four questions posed at the beginning of this chapter should now be fairly clear. What is a healthy lifestyle? A healthy lifestyle consists of five essential elements: 1. Not smoking (0 cigarettes) 2. Five (5) servings of fruits and vegetables daily 3. 10 minutes of relaxation, silence, or meditation daily for stress reduction 4. BMI less than 30 kg/m2 5. 150 minutes of exercise over the course of each week. This list may be communicated succinctly to patients by the simple numeric mnemonic 0-5-10-30-150. What is the prevalence of a healthy lifestyle among patients? For the general U.S. population, the prevalence of a healthy lifestyle defined by the four criteria above is 3%. This means that a large number of patients could benefit by being encouraged to adopt a healthy lifestyle. What are the potential benefits for patients who have or who change to a healthy lifestyle? The potential benefits of a healthy lifestyle are: 1. A 40% to 65% reduction in all-cause mortality. 2. An 81% to 87% reduction in coronary heart disease events. 3. A 67% reduction in all cardiovascular diseases. 4. A 50% to 71% reduction in stroke. 5. A 58% to 93% reduction in the risk of developing type 2 diabetes. 6. A 36% to 60% reduction in cancer deaths. What is the major obstacle to lifestyle changes in a family physician’s office? The major obstacle to the behavioral changes required to live a healthy lifestyle is a lack of physician training and skills in motivational interviewing. This is the major challenge to the training of physicians for the 21st century. The effectiveness of improved training and greater organizational support in health care systems for healthy physician lifestyles, as well as enhanced listening and MI skills, should be a major focus of the primary care research agenda for the future.


EVIDENCE-BASED SUMMARY • Individual global cardiac risk assessment performed regularly and followed by appropriate graded interventions is the most effective strategy for preventing heart disease (SOR: C). • Living a healthy lifestyle or changing to one is potentially more effective than focused cardiac risk reduction, because it not only reduces adverse cardiac events and death to a similar degree, but also is associated with major reductions in chronic diseases (diabetes, stroke, all cardiovascular disease, and even cancer) as well as large proportional reductions in all-cause mortality (SOR: B). • A healthy lifestyle consists of the following: Not smoking (SOR: A) 5 servings of fruits or vegetables each day (SOR: B) 10 minutes of relaxation, silence, or meditation each day (SOR: C) Maintaining a BMI less than 30 kg/m2 (SOR: B) • The most promising new technique of active listening to assist patients in making behavioral changes is motivational interviewing (SOR: C).

References The complete reference list is available online at www.expertconsult.com.

Web Resources http://webapp.cdc.gov/sasweb/ncipc/leadcaus.html Centers for Disease Control and Prevention (CDC) Wisqars database of U.S. deaths by cause, gender, age, ethnicity, and region. U.S. Preventive Services Task Force (USPSTF, AHRQ) reports on breast, cervical, colon, and prostate cancer: www.ahrq.gov/clinic/3rduspstf/breastcancer/brcanrr.htm www.ahrq.gov/clinic/3rduspstf/cervcan/cervcanrr.htm www.ahrq.gov/clinic/uspstf08/colocancer/colors.htm#rationale www.ahrq.gov/clinic/uspstf08/prostate/prostaters.htm Web-based cardiac global risk calculators: http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof Interactive Framingham Cardiac Risk Calculator. www.qrisk.org United Kingdom Q-Risk Calculator. www.health.gov/paguidelines/Report/Default.aspx U.S. Activity Guidelines for Adults (2008). www.kphealtheducation.org/bnroadmap/index.html Brief Negotiation Roadmap: Behavioral Tools for Practitioners, Kaiser Health Foundation. A log-in (free) is required, but access is

open to the public. This site includes interactive demonstrations, videos, and various tools for behavior change; a good place to start in learning the techniques of motivational interviewing. www.signup4.net/Public/ap.aspx?EID=DONT10E A list of courses in motivational interviewing offered by Kaiser Regional Health Education; regularly updated. www.motivationalinterview.org/ Motivational interviewing resources for clinicians, researchers, and trainers. www.Kopes-eticHealth.com The author’s personal website featuring collected work on primary prevention, cardiac risk reduction, and other topics. http://community.icontact.com/p/kopes-etichealth/newsletters/kopesetichealth Archive of all the author’s electronic newsletters for primary care physicians: FP Revolution. This electronic newsletter is published free twice monthly. You may sign up at www.Kopes-eticHealth.com.

111

8 CHAPT ER Interpreting the Medical Literature: Applying Evidence-Based Medicine in Practice Jeff Susman, Bernard Ewigman, Keith B. Holten, and Douglas R. Smucker

Chapter contents Building Clinical Evidence from Published Research Case-Control Studies Cohort Studies Structured Reviews and Meta-Analysis The Power of Randomized, Controlled Trials

Understanding the Statistical Significance of Study Results

112 113 113 113 113

114

Key Points • Interpreting the medical literature is a task any physician can do, particularly when using common, evidence-based summaries that are available at low or no cost. • The studies should report statistically significant results that are applicable to the physician’s population of patients and that should evaluate important patient-oriented outcomes, including potential harms. • When potentially changing practice behavior, the physician should assess whether the evidence is from high-quality studies replicated over time. • The medical literature is an evolving body of evidence, and each physician should develop a personal plan to keep up with important changes in medicine and strategies to answer more immediately important clinical questions at the point of care. • Using summary measures, such as the number needed to treat or harm and attributable risk, can make decisions about patient care more collaborative and transparent

Building Clinical Evidence from Published Research Evidence-based medicine (EBM)—asking clear, relevant clinical questions, finding appropriate studies, critically appraising the literature, and implementing changes in practice behavior—has become an essential part of medical care. Most busy physicians do not have the time or the background to answer critically the questions that arise in ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10008-9

Interpreting Study Results: Statistical and Clinical Significance 115 Other Keys to Interpreting Clinical Evidence

115

Using Evidence at the Point of Care

116

Case Example Evidence Levels

116 119

practice. Primary care physicians identify 2.4 clinical questions for every 10 encounters (Barrie and Ward, 1997), but they spend less than 15 minutes on average with each patient. Evidence about common primary care problems is accumulating at an overwhelming pace, and the broad scope of family medicine presents important challenges. Other barriers to the use of EBM include lack of evidence that is pertinent to an individual patient, quick access to information at the point of care, and potentially negative impacts on the art of medicine (McAllister et al., 1999). How can diligent physicians narrow the gap between their current behaviors and best practices? In this chapter, hormone replacement therapy (HRT) for postmenopausal women is used as a case example to understand the evolution of medical practice and the changing landscape of evidence and to review concepts important to interpreting the medical literature. These concepts form the basis for practical EBM tools that family physicians can use to answer important clinical questions. In Chapter 10, information from the Women’s Health Initiative (WHI) about HRT is considered, and similar epidemiologic and statistical issues are covered. Chapter 10 emphasizes the importance of how risk data are framed or presented to the patient and the primacy of patient preference (i.e., ability to make informed decisions about therapy). Unfortunately, evidence concerning the ideal manner of presenting information to patients and clinicians and promoting informed decision-making is still scant. This chapter and Chapter 10 take a slightly different approach to similar clinical questions, and together, these two chapters provide the background for the motivated family physician

Interpreting the Medical Literature: Applying Evidence-Based Medicine in Practice

Observational studies Case series descriptions → Case-control studies → Cohort studies → Structured reviews of observational studies Intervention studies Small randomized trials → Meta-analysis of small RCTs → Larger randomized controlled trials → Progression of studies over time Figure 8-1 Common progression of research in building the strength of evidence; RCTs, randomized, controlled trials.

to better understand concepts of risk and probability and to foster enhanced physician-patient decision-making. Evidence for interventions such as HRT usually begins with observational studies, including unblinded case series, case-control studies, and cohort studies, and it culminates in randomized, controlled trials (RCTs) (Figure 8-1). To better understand how we arrived at the current clinical understanding of HRT and its effects on heart disease, we review the progression of research studies and evidence over the past 30 years. A series of observational studies in the 1970s and 1980s led to regular prescribing of HRT to prevent a number of significant health conditions in postmenopausal women.

Case-Control Studies Case-control studies are often the first step in a progression of building clinical evidence because they are relatively inexpensive and rapid studies to complete. Case-control studies always look backward in time (i.e., retrospective studies) to determine a statistical association between an exposure and an outcome. To complete a case-control study of the association of HRT and coronary heart disease (CHD), a researcher would identify a group of cases (i.e., women with CHD) and a group of controls (i.e., women without CHD) and look back in time to determine how many women in each group had taken HRT. The association between exposure (i.e., HRT) and outcome (i.e., CHD) in a case-control study is typically summarized by a statistical measure called an odds ratio. An odds ratio is an estimation of the true relative risk for the outcome in question. A common form of bias in a case-control study is recall bias: errors in accurately determining whether cases and controls had exposure to HRT in the past.

Cohort Studies Cohort studies are often the next step in building the strength of evidence regarding an association between an exposure and an outcome. Cohort studies typically look forward in time (i.e., prospective studies) and are generally more expensive and take longer to complete than case-control studies. However, they provide a more accurate estimate of the relative risk for women who take HRT and those who do not. A cohort study is also an observational study—one that observes outcomes in groups but does not assign participants to a particular exposure or treatment. In a cohort study of HRT and CHD, a researcher would identify a group of women taking HRT and a similar group of women who

have chosen not to take HRT, and the researcher would then follow them over time and count the number of CHD events. Because outcome events may be uncommon in each group and may take many months to occur, cohort studies often require large numbers of participants and long follow-up periods to show significant differences between groups. The primary statistical measure from a cohort study is relative risk. This is a ratio of the rate of CHD events among women who choose to take HRT divided by the rate among women who choose not to take HRT. A common form of bias in cohort studies related to prevention is the healthy user bias, when participants who choose one preventive measure (e.g., HRT) also tend to make healthier lifestyle decisions (e.g., diet, exercise) that may also prevent the measured outcome (i.e., CHD). Beginning with case-control studies and then using larger cohort studies, observational research showed that HRT might reduce the incidence of CHD, fractures, and colorectal cancer. These observational studies also suggested that the same therapy might cause harm, with a slightly increased risk of breast cancer, stroke, and venous thromboembolism. On balance, however, even a small positive impact of HRT on preventing CHD was thought to far outweigh the potential adverse effects of HRT.

Structured Reviews and Meta-Analysis After a number of studies are completed, whether cohort studies or initial small RCTs, these are often reviewed and summarized in publications called structured reviews. Occasionally, data from a series of studies are combined using a statistical technique called meta-analysis, which allows increased statistical power to determine the weight of evidence from a series of studies. The use of HRT was greatly increased during the 1990s based on a number of case-control and cohort studies and on three meta-analysis studies that further suggested that HRT was protective against CHD (Pettiti, 1998). In 1991, an editorial in the New England Journal of Medicine concluded that “a consensus of epidemiologic reports has demonstrated that women who are given postmenopausal estrogen therapy have a reduction of about 40% to 50% in the risk of ischemic heart disease as compared with women who do not receive such therapy” (Goldman and Tosteson, 1991). HRT became a de facto standard for postmenopausal women through the 1990s.

The Power of Randomized, Controlled Trials In RCTs, study participants are randomly allocated to two or more groups and then assigned to receive an intervention such as HRT or to receive no active treatment (i.e., placebo or to continue with their usual care). RCTs greatly add to the confidence of measured results because the structure of an RCT helps to eliminate many of the inherent biases that are in observational studies. For example, in cohort studies of HRT and CHD, it is hypothesized that women who choose to take HRT are generally healthier and have better healthy lifestyle practices than women who do not choose to take HRT. Because participants in an RCT are randomly assigned to treatment and control groups, they are less likely to have differences in other factors that might prevent or promote heart disease. 113

8

Interpreting the Medical Literature: Applying Evidence-Based Medicine in Practice

Table 8-1 Understanding Study Results

Table 8-2 Examples of Summary Rates from the Women’s Health Initiative (WHI) Study

Typical summary rates from randomized, controlled trials: Number of new cases of disease over a defined period Incidence rate = Number of persons at risk during the period Relative risk (RR) =

Incidence rate among the treated group Incidence rate among the placebo group

Summary measures that may be more meaningful for clinicians: Attributable risk (AR), or risk difference = (Incidence rate among treated group) − (Incidence rate among placebo group) Number needed to treat (NNT) or number needed to harm (NNH) = Reciprocal of AR, or 1 / AR

The decreased likelihood of a healthy user bias in an RCT may explain why HRT appeared to be protective in cohort studies but later proved to be harmful. Because RCTs have this inherent ability to remove many important potential forms of bias (but are not immune to biases themselves), a physician can have more confidence that they reflect the true association between the HRT treatment and CHD outcomes. Despite decades of work, dozens of observational studies, and structured reviews that strongly suggested a protective effect of HRT for CHD, a single, large RCT trumped them all and caused a sudden reversal in physicians’ prescribing behavior. The results of the WHI study, released in 2002, sent a shock wave through the medical community. For the first time, a large, randomized trial showed that HRT—given to otherwise fairly healthy postmenopausal women—caused a statistically significant increase in CHD events. Within days of the release of the WHI primary results, many women called their physicians to decide whether they should continue with HRT. Many physicians drastically changed their prescription of HRT based on the WHI; within 9 months, prescriptions of the most popular formulation of HRT decreased by as much as 61% (Majumdar et al., 2004). Perhaps more than any other single study in modern medical history, the WHI report dramatically changed a widespread, common medical practice.

Understanding the Statistical Significance of Study Results Reports from RCTs such as the WHI study frequently include relative risk as a summary measure of differences between the treatment and placebo groups (Table 8-1). To arrive at the relative risk, the researcher first measures the incidence rate of an outcome in each of the two study groups (i.e., treatment and placebo). The incidence rate for each group is a ratio of the number of new outcome events, such as CHD events, divided by the number of patients at risk for the outcome in that group over a specific period. In multiyear studies, the average annual incidence rate is often reported as a summary measure. In a placebo-controlled RCT, the relative risk is then calculated as a ratio of the incidence rate for the treatment group divided by the incidence rate for the placebo group (Table 8-2). 114

The following equations show how to take a summary rate commonly reported in published studies (i.e., relative risk) and calculate a summary measure (e.g., number needed to treat, number needed to harm) that may be more useful in describing the results to clinicians and patients. The example considers the average annual incidence rates and relative risk for coronary heart disease (CHD) events in the WHI study on the effects of hormone replacement therapy (HRT): Average annual incidence among HRT − treated women = 37 CHD events / year / 10,000 women Average annual incidence among placebo − treated women = 30 CHD events / year / 10,000 women

Relative Riskof CHD =

37 CHD events / 10,000 women = 1.29 (adjusted) 30 CHD events / 10,000 women

The relative risk describes a relative 29% increase in CHD events. It may be more useful to consider the absolute difference in incidence rates between the two groups to understand the magnitude of the potential risk for a given patient: Attributable risk (AR) = =

37 CHD events 30 CHD events − 10,000 women 10,000 women 7 additional CHD events 10,000 women

The number needed to harm (NNH) can be calculated to describe, on average, how many women must be treated for 1 year to cause one additional CHD event attributable to HRT: NNH =

1 10,000 = = 1430 7 CHD events / 1000 women 7

Data from Ebell MH, Messimer SR, Barry HC. Putting computer-based evidence in the hands of clinicians. JAMA 1999;28:1171-1172.

How can a physician determine whether the reported relative risk from a study is significant enough to influence clinical decisions? Typically, the statistical significance of the summary measure is reported, which in this case is relative risk. Statistical significance is usually summarized in published studies by a p value for a given summary measure. The p value describes the statistical probability that the observed difference between the groups could have happened simply by chance alone. A p value of less than 0.05 is the arbitrary cutoff most often used for “statistical significance.” A “p AST include autoimmune hepatitis, hemochromatosis, alpha-1 antitrypsin disease, Wilson’s disease, metastatic disease, and cholestatic liver disease. Mild aminotransferase elevations with AST > ALT are more suggestive of alcohol-related liver disease, but can also occur with cirrhosis and fatty liver. With alcoholic hepatitis, AST levels typically are approximately twice ALT levels, but the AST levels rarely are greater than 300 U/L. Marked elevations (greater than 15 times upper limit of normal) of AST and ALT suggest significant necrosis, such as seen in acute viral or drug-induced hepatitis, in ischemic hepatitis, or as can occur with acute biliary obstruction (Green and Flamm, 2002). However, the magnitude of elevation of the aminotransferases does not necessarily correlate with the severity

of underlying liver disease or the prognosis. In fact, normal or minimally elevated aminotransferases may be seen in patients with end-stage liver disease. When AST is elevated without elevation of ALT, one should consider extrahepatic causes, particularly myocardial or skeletal muscle sources. When AST and ALT are elevated approximately the same, a hepatic origin is most likely. Table 15-6 compares the differences in liver function tests between hepatocellular and obstructive disorders. Lactate dehydrogenase (LDH) is elevated in liver disease but is nonspecific; it is also found in skeletal muscle, cardiac muscle, blood, and some pulmonary disorders. Measurement of LDH rarely adds useful information to the evaluation of liver disease. GGT is a microsomal enzyme that is inducible by alcohol and certain drugs, including warfarin and some anticonvulsants. Although not specific for alcohol abuse, GGT is the most sensitive liver enzyme for alcohol abuse.

Amylase and Lipase Pancreatic disease, particularly acute pancreatitis, is often associated with elevations in amylase and lipase. Table 15-7 lists common causes of elevated amylase and lipase. Lipase levels have greater sensitivity and specificity for pancreatic disease than amylase levels. Because there are many different assays for amylase and lipase, with different reference ranges, physicians should consult their laboratory’s reference range to determine their upper limits of normal. Amylase and lipase values increase 3 to 6 hours after the onset of acute pancreatitis, both peaking at approximately 24 hours. Amylase levels fall to normal in 3 to 5 days; lipase levels return to normal in 8 to 14 days. Because of exocrine insufficiency caused by recurrent pancreatitis, amylase levels tend to be lower when alcohol is the cause of pancreatitis, as opposed to gallstone or drug-induced pancreatitis. Pancreatitis is likely when the amylase is elevated to three times the upper limit of normal. When lipase levels are more than five times normal, pancreatitis is virtually always present. A normal amylase value, however, does not exclude pancreatitis, especially when induced by hypertriglyceridemia.

Antinuclear Antibodies Antinuclear antibodies (ANAs) are autoantibodies against parts of the cell’s nucleus. Combined with clinical features, ANA testing can help diagnose certain collagen vascular 181

15

Interpreting Laboratory Tests

Table 15-7 Causes of Elevated Amylase and Lipase Levels

Amylase

Lipase

Pancreatic Diseases Acute pancreatitis Chronic pancreatitis Pancreatic pseudocyst Pancreatic cancer Pancreatic trauma

ANA very useful for diagnosis Systemic lupus erythematosus

Acute pancreatitis Chronic pancreatitis

Systemic sclerosis

ANA somewhat useful for diagnosis Sjögren’s syndrome Polymyositis-dermatomyositis

Nonpancreatic Diseases Salivary gland disorders Intestinal perforation, ischemia, or obstruction Diabetic ketoacidosis Perforated peptic ulcer Ruptured ectopic pregnancy Renal failure Macroamylasemia Pregnancy

Table 15-8 Conditions Associated with Positive Antinuclear Antibody (ANA) Test

ANA very useful for monitoring or prognosis Acute cholecystitis Intestinal infarction Perforated peptic ulcer Renal failure

Drug-associated lupus Mixed connective tissue disease Autoimmune hepatitis

ANA not useful or has no proven value for diagnosis, monitoring, or prognosis Rheumatoid arthritis

disorders (Table 15-8). The likelihood that an ANA test will help with diagnosis depends on the pretest probability of disease. ANA tests are reported as negative (no staining) or positive at the highest cutoff of dilution of the serum that shows immunofluorescent nuclear staining. If positive, the description of the pattern is noted. When the ANA test is positive, testing for specific nuclear antigens should be guided by the clinical findings. Although the ANA is 95% sensitive for systemic lupus erythematosus (SLE), it is not specific and is seen in other diseases. Higher titers are more specific for SLE but may be seen in the other autoimmune diseases. About 20% of normal people have an ANA titer of 1:40 or higher, and 5% have a titer of 1:160 or higher. Less than 5% of patients with definite SLE have a negative ANA titer. Because of the high prevalence of positive ANAs in normal people, physicians need to reserve the diagnosis of SLE for patients who have clinical findings compatible with SLE. ANA titers correlate poorly with relapses, remission, and severity of disease and are not helpful in monitoring the course or response to therapy. ANA testing should be ordered when a connective tissue disease is considered, but it is not generally helpful in the evaluation of nonspecific complaints, such as fatigue or back pain (Solomon et al., 2002). For patients with a positive ANA titer, further testing for specific nuclear antibodies can be obtained, guided by the pattern of ANA staining and the clinical findings. The interpretation of testing for specific nuclear antigens can also be difficult; most of the “specific” antigens are not 100% specific for a particular disease and need to be interpreted in the clinical context. The anti-DNA test is highly specific for SLE, with about 95% specificity but only 50% to 60% sensitivity, and it can be used as a confirmatory test in patients with a positive ANA. Similarly, the anti-Sm (Smith) test is also highly specific for SLE, but with 30% sensitivity. Anti-SSA/Ro and anti-SSS/La are often used to diagnose Sjögren’s syndrome but can also be found in SLE. Anti Scl-70 is found in scleroderma but is not a requirement for diagnosis. 182

Multiple sclerosis Thyroid disease Infectious diseases Idiopathic thrombocytopenia purpura Fibromyalgia From Solomon DH, Kavanaugh AJ, Schur PH, et al. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum 2002;47:434-444.

Bilirubin Bilirubin is produced by catabolism of hemoglobin in extrahepatic tissues. Hepatocytes conjugate the bilirubin, and it is then excreted into bile. Blood bilirubin levels are a function of production rate and biliary excretion. Total bilirubin is a combination of lipid-soluble unconjugated bilirubin and water-soluble conjugated bilirubin. Total bilirubin is less than 1.5 mg/dL and is normally primarily unconjugated bilirubin. The initial step in the evaluation of an elevated bilirubin level is to distinguish conjugated (direct) from unconjugated (indirect) hyperbilirubinemia. Probably the most common cause of unconjugated hyperbilirubinemia is Gilbert’s syndrome, a benign condition that affects up to 5% of the population. In Gilbert’s syndrome, only the unconjugated bilirubin is elevated; the rest of the liver enzymes are normal. Other causes of unconjugated hyperbilirubinemia include hemolysis, ineffective erythropoiesis (as in megaloblastic anemias), or a recent hematoma. With normal hepatic function, hemolysis is not associated with bilirubin levels greater than 5 mg/dL. In an asymptomatic person with mildly elevated unconjugated hyperbilirubinemia (100 fL) is present. Vitamin B12 and folate deficiency causes a megaloblastic anemia, which is one type of macrocytic anemia. The hematologic picture is identical for both folate and vitamin B12 deficiency. Megaloblasts are enlarged blastic cells (precursors to the erythroid and myeloid cell lines) found in the bone marrow and caused by aberrant DNA synthesis. The peripheral blood smear typically shows the presence of oval macrocytes, hypersegmented neutrophils (>5% neutrophils with 5 lobes or any neutrophil with 6 lobes). Anisocytosis (size variation) and poikilocytosis (shape variation) of the red blood cells (RBCs) are often present, so the RBC distribution width (RDW) is increased. The reticulocyte count is usually decreased. Thrombocytopenia is present in 12% and leukopenia in 9% of cases; occasionally, B12 or folate deficiency will present with pancytopenia. Coexisting disease such as iron deficiency, inflammatory process, renal failure, or thalassemia trait also may normalize the mean corpuscular volume (MCV) value in the patient with vitamin B12 or folate deficiency. The clinician must distinguish folate from B12 deficiency, because supplementing one will not correct the symptoms from deficiency of the other, i.e., folate replacement will not improve the neuropsychiatric abnormalities caused by vitamin B12 deficiency. The neurologic signs and symptoms, such as paresthesias, memory loss, dementia, and weakness, may precede hematologic abnormalities. Vitamin B12 and folate deficiency often coexist because some causes overlap (Table 15-11). Because vitamin B12 is a cofactor in the conversion of methylmalonic acid to succinyl coenzyme A (CoA) and homocysteine to methionine, deficiencies of vitamin B12 will lead to increased levels of methylmalonic acid and homocysteine. Folate is required in the conversion of homocysteine to methionine, but not in the conversion of methylmalonic acid to succinyl CoA. Folate deficiency is associated with elevated homocysteine, but not methylmalonic acid. The reference range for vitamin B12 is often listed as 200 to 900 pg/mL;

however, it is now recognized that a significant portion of patients with vitamin B12 levels of 200 to 400 pg/mL have symptoms of vitamin B12 deficiency. Folate levels greater than 4 ng/mL are considered normal; levels of 2 to 4 ng/mL are indeterminate. A person in negative folate balance will become serum deficient before tissue folate stores decrease; therefore a low serum folate level indicates a negative folate balance, but not necessarily tissue folate deficiency. Intake of folate may normalize serum levels initially, so serum folate levels should be determined before a hospitalized or potentially deficient patient is fed, takes vitamins, or is given a transfusion. Measuring RBC folate levels is not recommended because it is difficult to interpret. Instead, testing for methylmalonic acid and homocysteine can help determine if patients with levels in the low-normal range actually have vitamin B12 or folate deficiency. Folic acid is absorbed in the upper small bowel, whereas B12 is absorbed mainly in the ileum with the help of intrinsic factor, which is secreted by the gastric parietal cells. Nutritional factors and malabsorption syndromes are principal reasons for deficiency of both vitamin B12 and folic acid. Hemolysis will falsely elevate serum folic acid levels.

Complete Blood Count The complete blood count (CBC) measures circulating blood cells, including RBCs, white blood cells (WBCs), and platelets (Table 15-12). Current technology uses electronic cell counters that can count and size the cells, providing an estimate of cell volume (MCV) and variation in cell size (RDW), and give a five-part WBC differential, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils (Tefferi et al., 2005). Typically, peripheral blood smears are prepared for manual review only when requested or when automated hematology analyzers flag abnormal results. By analyzing large numbers of cells, current instruments can generate more accurate data than by manual review for most parameters. Indications for manual review of a blood smear include the evaluation of hemolysis, RBC inclusions, myelodysplasia, megaloblastic changes, thrombocytosis, throm-

Table 15-11 Cobalamin (Vitamin B12) and Folate Deficiency

Most Common Cause

Vitamin B12 Deficiency

Folate Deficiency

Inadequate intake

Strict vegetarian diet (rare) Alcoholism, elderly patients

Malnutrition Alcoholism

Increased need

Pregnancy, lactation

Pregnancy, lactation, infancy Neoplasia, hyperthyroidism, hemolysis

Defective absorption or storage

Decreased intrinsic factor (e.g., pernicious anemia, congenital deficiency of intrinsic factor, gastrectomy) Zollinger-Ellison syndrome Pancreatitis Ileal mucosal disease (e.g., sprue, regional enteritis, surgery, lymphoma) Tapeworm infestation, other parasites Bacterial overgrowth in blind-loop syndrome Drugs (e.g., colchicine, aspirin, metformin)

Malabsorption caused by: Drugs (e.g., anticonvulsants, antituberculosis agents, oral contraceptives, folate antagonist) Jejunal mucosal disease (e.g., amyloidosis, sprue, lymphoma, surgery) Liver disease (cirrhosis, hepatoma)

186


bocytopenia, leukocytosis, and immature or abnormal cells (Bain, 2005).

Red Blood Cells A mild anemia is the most common abnormality found on a CBC. Factors that help determine whether further testing should be performed include the degree of anemia and the presence of other abnormalities in the CBC. The first step is to classify the anemia, based on MCV, as microcytic (100 fL). With a microcytic anemia, the most important test is the ferritin level, which is diagnostic of iron deficiency anemia when less than 12 ng/mL. With a normocytic anemia, potentially treatable causes should be excluded

(e.g., recent bleeding, hemolysis, renal insufficiency, vitamin deficiency). Other causes of a normocytic anemia (e.g., anemia of chronic disease, primary bone marrow disorder) may need a bone marrow biopsy for definitive diagnosis. For a macrocytic anemia, important determinations are the medication history, alcohol use, and vitamin B12 or folate deficiency. Erythrocytosis refers to a hematocrit above the reference range. In true erythrocytosis, the total circulatory RBC mass is increased, whereas in relative erythrocytosis, the RBC mass is normal, but the plasma volume is decreased, so the hematocrit is elevated. With true erythrocytosis, elevated erythropoietin levels suggest a secondary cause and can help distinguish secondary erythrocytosis from polycythemia vera (Table 15-13).

Table 15-12 Complete Blood Count Components

95% Reference Range Conventional

Reference Range International

Measure of oxygen-carrying capacity of blood expressed as grams per unit volume (usually deciliters; g/dL).

M: 13.5-17.5 g/dL F: 12.0-16.0 g/dL

135-175 g/L 120-160 g/L

Hematocrit (Hct)

Measure of solid elements of blood (mostly RBCs), as percentage of whole blood (remainder is plasma). Hct = MCV × RBC. Expressed in%, usually about three times Hb. Both Hct and Hb usually are low in anemia, but may not be apparent early in acute blood loss, because plasma volume needs about 12-24 hours to equilibrate.

M: 39%-49% F: 35%-45%

0.39-49, volume fraction 0.35-0.45, volume fraction

Red blood cell (RBC) mass

Erythrocyte count; true measure of cells/L.

M: 4.3-5.7 × 106 cells/μL F: 3.8-5.1 × 106 cells/μL

4.3-5.1 × 1012 3.8-5.1× 1012

Red cell indices

MCH, MCHC, MCV. Note: In early anemia, MCV may change before Hb and Hct.

Mean corpuscular hemoglobin (MCH)

Hb divided by RBC; represents the content (weight) of Hb in average RBC; not as useful as MCHC.

26-34 pg/cell

0.40-0.53 fmol/cell

Mean corpuscular hemoglobin concentration (MCHC)

Hb divided by Hct, concentration of Hb per unit volume of packed RBCs. Appearance of erythrocytes on peripheral smear is affected by Hb concentration in cell; low, hypochromic; normal, normochromic; high, hyperchromic.

31.37% Hb/cell or g Hb/dL RBCs

4.81-574 mmol Hb/L RBCs

Mean corpuscular volume (MCV)

Hct × 1000 divided by the RBC count; reflects RBC size; small, microcytic; normal, normocytic; large, macrocytic. Note: Presence of microcytosis and macrocytosis in same sample may result in normal MCV.

80-100 fL 1fL (femtoliter) = 10−15 L = 1 cubic micrometer (μm3)

80-100 fL

Red cell distribution width (RDW)

Estimate of RBC size variability (anisocytosis); standard deviation (SD) of RBC size divided by MCV.

11.5-14.5

11.5-14.5

Reticulocyte count (%)

Expressed as percent of reticulocytes per 1000 RBCs counted.

0.5%-1.5%

0.005-0.015 (number fraction)

Reticulocyte count (absolute)

Reticulocyte (%) × RBC count; more meaningful expression of erythropoiesis.

50 × 103/μL

50 × 109/L

150-450 × 103/μL

150-450 × 109/L

Test

Description

Hemoglobin (Hb)

Platelet count

187

15


Table 15-13 Classification of Erythrocytosis

Relative Erythrocytosis Diminished plasma volume Spurious polycythemia

Absolute Erythrocytosis Genetic disorders Familiar polycythemia Primary marrow disorders Polycythemia vera Secondary conditions with appropriately increased erythropoietin High altitude, pulmonary disease, congenital heart disease, sleep apnea syndrome, carboxyhemoglobin High-affinity hemoglobin Secondary conditions with inappropriately increased erythropoietin production Erythropoietin producing tumors (renal carcinoma, cerebellar hemangioma, hepatoma) Polycystic kidney disease Modified from Cazzolo M. Serum erythropoietin concentration as a diagnostic tool for polycythemia vera. Haematologica 2004;89:1160.

White Blood Cells The WBC count is often requested to support a diagnosis of infection or an inflammatory process. The WBC count is useful as a means of monitoring the course of a disease or response to treatment. The cell types that make up the WBC count include neutrophils (segmented and band forms), lymphocytes, monocytes, eosinophils, and basophils. Bands are immature neutrophils, and segmented forms are mature neutrophils. To diagnose neutropenia, the absolute neutrophil count (ANC) should be determined. The ANC is obtained from the cell counter or calculated by multiplying the total WBC count by the percentage of bands plus mature neutrophils (segmented forms): ANC = WBC count × ( % Bands + % Segmented forms)

When severe neutropenia, the ANC drops below 500 cells/ mm3, and the patient is at risk for infections. Causes of neutropenia include drug reactions, bacterial and viral infections, hematopoietic diseases, cachexia, hypersplenism, and autoimmune diseases. Lymphocytopenia is present when the lymphocyte count is less than 1500 cells/mm3 in the adult or 3000 cells/mm3 in children. Causes of lymphocytopenia include immunosuppressant drugs, corticosteroid therapy, viral infections (including HIV), and genetic immunodeficiencies. Leukocytosis, or an elevated WBC count, occurs when the total WBC count is greater than 10,000 cells/mm3. An elevated WBC count may be the result of a reactive process (leukemoid reaction) or leukemia. Leukemoid reactions can 188

result from infections, toxic conditions, neoplasms, myeloproliferative diseases, and other hematologic disorders. The first step in the evaluation of leukocytosis is to determine what type of WBC is elevated. Leukocytosis may be caused by neutrophilia, eosinophilia, basophilia, monocytosis, or lymphocytosis (Table 15-14).

Platelets Platelets, cellular fragments of the bone marrow precursorcell megakaryocytes, are essential to clot formation and have a life span of about 10 days. Clinically, a disorder in platelets is usually suspected in a patient with excessive bleeding, typically from a mucocutaneous source or after trauma. Clinical evidence of bleeding does not occur until the platelet count drops below 50 to 70 × 103/μL. Platelet counts of less than 10 to 20 × 103/μL are associated with major spontaneous bleeding. Thrombocytopenia may be caused by disorders of production, distribution, or destruction (Table 15-15). In evaluating thrombocytopenia, first examine the peripheral smear for platelet clumping, or repeat the test using sodium citrate as the anticoagulant. Thrombocytosis, or an increased platelet count, may be caused by a reactive process or a myeloproliferative disorder. Reactive processes do not usually produce platelet counts greater than 1000 × 103/μL. Common causes of thrombocytosis include iron deficiency, acute blood loss, inflammatory disorders, malignancies, splenectomy, and myeloproliferative disorders.

Carbon Dioxide or Bicarbonate Acid-base disturbances are often recognized by abnormalities in the carbon dioxide (CO2) content of blood, which is composed primarily of bicarbonate (HCO3−), with small amounts of carbonic acid and dissolved carbon dioxide. The reference range for CO2 is 22 to 29 mmol/L. A reduced serum bicarbonate concentration frequently suggests metabolic acidosis, particularly when combined with a low pH. An elevated serum bicarbonate level frequently occurs with metabolic alkalosis. Bicarbonate is often used as a buffer for excess acid production, and levels are reduced in metabolic acidosis. In the evaluation of acidosis, calculation of the serum anion gap is helpful in determining the cause of the acidosis, as follows: Anion gap = Na − (Cl + CO2 )

The normal range is 10 to 12 mmol/L. An increased anion gap generally indicates the presence of metabolic acidosis with elevation of unmeasured ions, such as lactic acid, phosphates, sulfates, and ketoacids. A normal anion gap acidosis is seen with bicarbonate losses and increased chloride resorption and most frequently occurs with chronic diarrhea, but also with certain types of renal tubular acidosis. Low anion gaps can occur with hypoalbuminuria, congestive heart failure, and occasionally, multiple myeloma. An elevated serum bicarbonate level frequently occurs in the setting of metabolic alkalosis. Metabolic alkalosis can be generated by loss of acid, such as in vomiting, but normally the kidney corrects the abnormality promptly by excreting excess bicarbonate. To maintain a metabolic alkalosis, the kidney must not be able to excrete excess bicarbonate. This


Table 15-14 Common Causes of Leukocytosis or Leukopenia Stratified by White Blood Cell (WBC, Leukocyte)Type

Condition

Description

Leukocytosis Neutrophilia

Infections, leukemia, rheumatic and autoimmune disorders, neoplastic disorders, chemicals, trauma, endocrine and metabolic disorders, hematologic disorders, drugs

Eosinophilia

Infectious diseases, parasitic infections, allergic diseases, myeloproliferative and neoplastic diseases, cutaneous diseases, gastrointestinal diseases

Basophilia

Allergic reactions, chronic myeloid leukemia, myeloid metaplasia, polycythemia vera, ionizing radiation, hypothyroidism, chronic hemolytic anemia, splenectomy

Monocytosis

Infections, neoplastic disorders, gastrointestinal disorders, sarcoidosis, drug reactions, recovering from marrow suppression

Lymphocytosis

Viral infections, lymphocytic leukemia, other infectious diseases, neoplastic disorders

Leukopenia Neutropenia

Overwhelming bacterial infection, viral infection, drug reaction, ionizing radiation, hematopoietic diseases, hypersplenism, anaphylactic shock, cachexia, autoimmune disease

Eosinopenia

Acute stress (usually physical), acute inflammatory states, Cushing’s syndrome, corticosteroids

Basopenia

Sustained treatment with glucocorticoids, acute infection or stress, hyperthyroidism

Monocytopenia

Onset of steroid therapy; hairy cell leukemia

Lymphocytopenia

Immunodeficiency disorders, adrenocortical hormone excess, chemotherapeutic drugs, irradiation, impaired drainage of intestinal lymphatics, advanced lymphomas and carcinomas

From Speicher CE. The Right Test, 3rd ed. Philadelphia, Saunders, 1998.

abnormality usually occurs in the setting of volume depletion, when sodium reabsorption is enhanced and the sodium must be accompanied by an anion to maintain electroneutrality. In the absence of available chloride in the urine, bicarbonate is reabsorbed with sodium, thereby maintaining the alkalosis. As mentioned earlier, urine chloride levels can assist in determining the cause of the metabolic alkalosis.

C-Reactive Protein An acute-phase reactant glycoprotein, C-reactive protein (CRP) is associated with inflammation. CRP is one of the first proteins to become elevated after an inflammatory process has begun and disappears rapidly when inflammation subsides. In healthy persons, CRP levels are usually less than 0.8 mg/L and are often below the detection limit for standard assays. Serum levels may increase dramatically to exceed 100 mg/L in the presence of bacterial and viral infections, inflammation, severe trauma, surgery, neoplastic proliferation, tissue injury, or necrosis, and transplant rejection. Moderate elevations may be seen with myocardial infarction, autoimmune diseases, rheumatic fever, pregnancy, and postoperatively, as well as in obese persons and women taking estrogen replacement therapy or with an intrauterine device in place. CRP is not affected by age, race, or food intake and does not have significant circadian variation. Drugs that may reduce or suppress CRP levels by controlling inflammation include statins, fibrates, niacin, nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, salicylates, angiotension-converting enzyme (ACE) inhibitors, and beta-adrenergic blockers. CRP has some advantages over erythrocyte sedimentation

rate (ESR). The CRP rises before the ESR, returns to baseline sooner, and is less influenced by altered physiologic states. The levels of CRP used to assess atherosclerotic risk are much lower than those associated with inflammation (Myers et al., 2004). More sensitive immunoassays were developed to measure levels lower than those detected in conventional assays. These highly sensitive CRP tests (hsCRP; Cardiac-CRP) can accurately measure to a lower limit of 0.3 mg/L. Many studies have found that hsCRP levels predict the long-term risk of myocardial infarction, ischemic stroke, peripheral vascular disease, and all-cause mortality in healthy subjects. The hsCRP also predicts outcomes in patients with stable coronary artery disease, acute coronary syndromes, and after percutaneous coronary intervention. In 2004 the American College of Cardiology and American Heart Association (AHA) recommended hsCRP testing to further evaluate patients judged to be at intermediate risk for the development of coronary heart disease (those with 10-year CHD risk of 10% to 20%). CRP levels are divided into tertiles: low risk (3.0 mg/L). A CRP in the highest tertile is associated with a twofold risk of major coronary events compared with a CRP in the lowest tertile. Unexplained levels of hsCRP levels higher than 10 mg/L should be repeated and evaluated for noncardiovascular causes, such as infection or inflammation (Smith et al., 2004).

Erythrocyte Sedimentation Rate The ESR is one of the oldest laboratory tests still in clinical use. The test measures the distance that erythrocytes (RBCs) fall in a column of anticoagulated blood in 1 hour. Plasma 189

15


Table 15-15 Causes of Thrombocytopenia

Decreased Production

Table 15-16 Factors Affecting the Erythrocyte Sedimentation Rate (ESR)

Increase

Decrease

No Effect

Radiation or chemotherapy

Anemia

Polycythemia

Body temperature

Vitamin B12 or folate deficiency

Macrocytosis

Microcytosis

Recent meal

Drugs

Female gender

Spherocytosis

Aspirin

Systemic lupus erythematosus

Advanced age

Extreme leukocytosis

NSAIDs

Aplastic anemia

Sickle cell disease

First-trimester pregnancy

Acute leukemia

Second- and third-trimester pregnancy

Lymphomas

Hypoalbuminemia

Excessive anticoagulant

Alcohol abuse

Tilted ESR tube

Short ESR tube

Viral infections (including HIV)

High room temperature

Low room temperature Clotted blood sample

Congenital disorders

Increased Destruction Immune thrombocytopenia

NSAIDs, Nonsteroidal anti-inflammatory drugs.

Drugs Quinine Quinidine Heparin Sulfa drugs Valproic acid Disseminated intravascular coagulation (DIC) Hemolytic-uremic syndrome Hemolysis, liver dysfunction, and low platelets (HELLP syndrome) Sepsis Cardiopulmonary bypass Toxemia of pregnancy, eclampsia

Splenic Sequestration

proteins known as acute-phase reactants facilitate erythrocyte aggregation, which in turn affects the rate at which the solid component of blood will settle in a capillary tube. The plasma proteins most responsible for this aggregation (rouleaux formation), in decreasing order, are fibrinogen, beta (β-) globulins, alpha (α-) globulins, gamma (γ-) globulins, and albumin. Inflammatory, infectious, neoplastic, and collagen vascular diseases increase the ESR. The ESR is helpful in the diagnosis of polymyalgia rheumatica and temporal arteritis; otherwise, it is both nonsensitive and nonspecific. In studies of patients with biopsy-proven temporal arteritis, 90% of patients had an ESR greater than 30 mm/hr with mean ESR of 90 mm/hr. About 4% of patients with biopsy-proven temporal arteritis have a normal ESR (Smetana and Shmerling, 2002). When there is strong clinical evidence for temporal arteritis and a normal ESR, however, a temporal artery biopsy or a trial of corticosteroids should be considered. Although 190

used to follow the response to corticosteroid therapy in polymyalgia rheumatica and temporal arteritis, ESR should be used in conjunction with clinical findings. Typically, ESR drops within a few days of corticosteroid therapy, falling to a level that is higher than normal. In addition, relapse can occur without ESR elevation. Table 15-16 lists physiologic, pathologic, and technical factors that alter ESR, which is higher in women than men and higher in older persons. To determine ESR for healthy adult men, age in years is divided by 2, and for women, age in years plus 10, divided by 2. Clinical considerations for using ESR have been defined (Brigden, 1998; Sox and Liang, 1986). It should not be used as a screening test for disease in asymptomatic persons. As a single test after a normal history and physical examination in asymptomatic persons, ESR contributes to disease detection of a serious illness in less than 6 of 10,000 persons. The underlying cause of an elevated ESR is usually apparent by the history and physical examination, especially for extreme elevations of about 100 mm/hr. Many cases of unexplained elevated ESR are transient and not associated with serious disease. If no obvious cause is seen for elevated ESR, repeating the test in several months is recommended, rather than searching for occult disease.

Fecal Occult Blood Test The fecal occult blood test (FOBT) is used to detect blood loss in the stool that is not clinically apparent. Patients who report rectal bleeding or those with frank blood by rectal examination should undergo further diagnostic evaluation and do not need an FOBT. Although mainly used to screen for colorectal cancer, the FOBT is not specific for colorectal cancer. The two main FOBTs commercially available are the guaiac-based tests, which detect pseudoperoxidase in the heme portion of hemoglobin, and the more expensive immunochemical tests, which detect the globulin portion of human hemoglobin. Most RCTs using the FOBT as a screening test


for colorectal cancer used guaiac testing. Newer methods using immunochemical testing are also used in clinical practice. Stool assays that identify colon neoplasia are still being developed and tested. Guaiac FOBT kits include Hemoccult and Hemoccult II SENSA; Hemoccult II has been widely used in clinical practice as well as RCTs. The basis of the guaiac test is that the pseudoperoxidase of hemoglobin oxidizes guaiac to form a blue-colored quinone compound, after the addition of a hydrogen peroxide developer. The likelihood of a positive guaiac test is related to the amount of blood present in the stool. Normally, about 0.5 to 1.5 mL of blood is lost daily into the GI tract. The FOBT test requires approximately 2 mL/day of blood to be positive; to be consistently positive requires more. Several factors have an impact on FOBT performance characteristics. Bleeding from proximal gastrointestinal lesions, including the right colon, may allow for degradation of the heme, which will then not catalyze the guaiac reaction. The myoglobin or hemoglobin in red meat can give a false-positive reaction, although ingesting 8 oz of cooked red meat daily has only a 5% probability of giving a positive test result. Peroxidaserich raw vegetables and fruits (turnips, parsnips, horseradish, artichokes, mushrooms, radishes, broccoli, cauliflower, beets, apples, oranges, bananas, melons, grapes, pears, plums, cantaloupe) may give a false-positive result if fecal specimens are tested immediately after collection. However, plant peroxidases are unstable with time; therefore, if a specimen is developed several days after collection, the likelihood of a false-positive test result because of plant peroxidases is reduced. Gastric irritants such as aspirin, NSAIDs, and excessive alcohol consumption may also produce positive results. Oral iron supplements and acetaminophen do not affect the guaiac test. Ascorbic acid (vitamin C) in excess of 250 mg/day or multivitamins with vitamin C may cause a falsenegative result because ascorbic acid is a reducing agent and interferes with the oxidation of guaiac. Other antioxidants should also be avoided. Antacids may also cause false-negative results. The processes of collecting and processing FOBTs are important in the evaluation of the results. Delaying the processing of the slides allows for dehydration of the specimen, which allows degradation of peroxidase activity and will decrease the sensitivity of testing. The delay between preparation and laboratory testing should not exceed 6 days. The issue of rehydration of dried slides with water is controversial. Rehydration of slides increases sensitivity and decreases specificity (false-positive rate increases). Rehydration increases the positivity rate of Hemoccult II fourfold, from 2% to 3% to 8% to 16% (10% average), but this rate can be minimized if the patient adheres to a low-peroxidase diet. Proper patient instruction and preparation are essential during collection of specimens (Bresalier, 2002). Patients should not collect specimens until 3 days after menses have stopped or if obvious rectal bleeding or hematuria is noted. For 3 days before testing, patients should avoid ingesting red meat, vegetables with high amounts of peroxidase (broccoli, turnip, cantaloupe, cauliflower, radishes), aspirin, NSAIDs, and vitamin C. The detection of the blue color of a positive test may be affected by other factors, including a thick stool smear, exposure to high ambient temperatures, and black stools from iron ingestion.

As a screening test for colorectal cancer, FOBT has low sensitivity and specificity. Other GI lesions, including hemorrhoids, angiodysplasia, diverticular disease, and upper GI lesions, can lead to increased blood in the stool. Bleeding from colon cancers can be intermittent or undetectable, and other factors can give false-positive or false-negative readings. About 2% to 6% of asymptomatic adults have a positive FOBT test, 10% of whom have cancer and 20% to 30%, adenomas. The rest have upper GI sources of bleeding, nonneoplastic lower GI sources of bleeding (e.g., hemorrhoids), or no identified source of bleeding. The sensitivity of the FOBT in patients with colon cancer is approximately 30%. With home-based testing, FOBT has best been studied using a regimen of three stools. Because only one specimen is obtained during a digital rectal examination (DRE), office collection is less sensitive than three at-home determinations. A study compared FOBT during DRE (without rehydration) in the office and home-based six-sample FOBT (with rehydration) to colonoscopy. The digital FOBT was positive in 6.4% of patients with adenomas with high-grade dysplasia and 9.5% of patients with cancer, whereas the home-based FOBTs were positive in 29.8% of patients with adenomas with high-grade dysplasia and in 42.9% of patients with cancer (Collins et al., 2005). A single digital FOBT has poor sensitivity and therefore cannot be recommended as the sole test for screening for colon cancer. Because of the concerns about sensitivity and specificity with the FOBT, new tests have been developed. With a change in the developer fluid, the Hemoccult SENSA is more sensitive than Hemoccult or Hemoccult II but less specific. Newer fecal immunochemical tests (FITs; Hema Select, FlexSure, Insure) have been developed to increase the sensitivity and specificity over FOBT. These tests are based on an antigen-antibody reaction that is specific for human hemoglobin. They do not react with animal hemoglobin or peroxide-containing foods. Moreover, the FIT is not affected by ingestion of vitamin C, iron, or rehydration, and testing can be delayed for up to 30 days. Therefore, dietary restrictions and specimen handling are not critical issues. The FIT can detect stool hemoglobin at one-tenth the concentration of the FOBT. Some brands (e.g., Insure) detect the globulin portion of hemoglobin, which is degraded in the upper GI tract. Therefore, these tests are more specific for identifying bleeding from the colon.

Glucose The reference range for a fasting plasma glucose level is between 70 and 99 mg/dL. Hypoglycemia is best documented by a plasma venous glucose level less than 50 mg/ dL, although there is considerable variability in the level of hypoglycemia that causes symptoms. Asymptomatic hypoglycemia in a patient not taking insulin or oral hypoglycemic agents may be a laboratory artifact caused by ongoing metabolism of glucose in the specimen, especially if a delay has occurred in processing the specimen. The diagnosis of hypoglycemia is best made with typical symptoms associated with a laboratory confirmation of venous hypoglycemia, followed by relief of symptoms after ingesting glucose. The glucose tolerance test (GTT) can produce hypoglycemia in normal persons and should not be routinely ordered in the evaluation of hypoglycemia. 191

15


Hypoglycemia can be defined as iatrogenic, postprandial, or fasting. Postprandial hypoglycemia occurs after meals and is usually mild and self-limiting. Alimentary hypoglycemia occurs when patients have rapid gastric emptying. Insulin levels rise rapidly after a meal and fall more slowly than glucose levels, which results in hypoglycemia. Fasting hypoglycemia is seen much less often than reactive hypoglycemia and may be a harbinger of more severe disease, including insulin-producing pancreatic tumors and hepatic, adrenal, or renal insufficiency, or it may be the result of excess insulin or sulfonylurea administration. True fasting hypoglycemia needs to be confirmed by a prolonged fast, with simultaneous measurement of glucose and insulin. This technique can help determine whether the hypoglycemia is associated with excess insulin. Diabetes mellitus is characterized by hyperglycemia. The American Diabetes Association has defined normal fasting plasma glucose as less than 100 mg/dL (5.6 mmol/L), prediabetes as 100 to 125 mg/dL (5.6-6.9 mmol/L), and diabetes mellitus as 126 mg/dL (7.0 mmol/L) or greater.

Glycosylated Hemoglobin (Hemoglobin A1c) The hemoglobin A1c (HbA1c) fraction measures nonenzymatic glycosylation of hemoglobin, which is related to level of glucose concentration over the life span of the erythrocyte. The HbA1c fraction can be used to estimate glucose control in the previous 3 months. In persons with normal erythrocyte survival, the glucose levels in the last 30 days contribute to 50% of the HbA1c, whereas the glucose levels in the preceding 90 to 120 days contribute only 10% to the HbA1c measurement. Although previously laboratories varied considerably in the reporting of HbA1c results, virtually all U.S. laboratories now have adopted the National Glycohemoglobin Standardization Program (NGSP) methods. Recent standards propose reporting HbA1c in the familiar percentage and in international units (mmol/mol), combined with the HbA1c-derived average glucose (ADAG) (Saudek et al., 2008). Using NHANES III data that the population average for HbA1c was 5.17 with standard deviation (SD) of 0.45, the International Expert Committee (2009) selected an HbA1c of 6.5% (~3 SD above average) as the cutoff point to diagnose diabetes mellitus, with confirmation by a fasting glucose greater than 126 mg/dL or oral GTT greater than 200 mg/ dL, or a repeat HbA1c greater than 6.5%. Goals for achieving optimal control of diabetes are controversial, but a reasonable goal in most persons is an HbA1c less than 7%. Conditions that shorten erythrocyte survival, such as hemolysis or recent bleeding, give a lower HbA1c level.

Helicobacter pylori A spiral, urease-producing bacterium, Helicobacter pylori is associated with almost 90% of duodenal ulcers. Testing is indicated in patients with either active or previously documented peptic ulcer disease, in the evaluation of dyspepsia who have no “alarm features,” and for patients with a history of gastric MALT (mucosa-associated lymphoid tissue) lymphoma (MALToma) (Chey and Wong, 2007). Several tests can be performed during endoscopy. Rapid urease testing of a biopsy specimen has sensitivity over 90% and specificity over 95%, with results available within 1 to 24 hours. The sensitivity of rapid urease tests is reduced by drugs that treat 192

H. pylori, including bismuth, antibiotics, and proton pump inhibitors (PPIs). Histologic examination of gastric biopsies can also detect H. pylori. Culturing H. pylori has a lower yield, is more expensive, and is not widely done. Serologic tests for immunoglobulin G (IgG) antibody to H. pylori are helpful in determining previous infection and have sensitivity of approximately 88% but specificity of only 70% to 80%. Even though titers may decline slowly after eradication of the organism with antibiotics, these tests have limited use in evaluation of the effectiveness of antibiotic therapy and cannot reliably distinguish current from past infection. The value of H. pylori antibody testing in the evaluation of uninvestigated dyspepsia depends on the prevalence of H. pylori infection. In areas of high prevalence (>20%), serologic testing may be cost-effective for a test-and-treat strategy. Antibody testing is inexpensive and has a very good negative predictive value. Urease breath tests using carbon 13 (13C)–urea or 14C-urea can detect ongoing replication of H. pylori. These tests are most helpful in determining whether H. pylori has been successfully eradicated after a course of treatment, but they can also confirm active infection in the presence of positive serologic findings. After the ingestion of labeled urea, urease-producing H. pylori organisms break down the urea and produce labeled CO2, which is absorbed into the circulation and exhaled, and can be measured by collecting an exhaled breath sample in a bag. False-negative breath tests may occur with the recent use of antibiotics, bismuth, or PPIs. Most studies find the sensitivity and specificity of the urease breath test to be greater than 95%. Testing for H. pylori antigen in the stool by ELISA assays has been found to have sensitivity over 90% and specificity approaching 100%, thereby making it an accurate noninvasive method to diagnose active H. pylori infection in untreated patients. As in urease breath testing, recent antibiotics, PPIs, and bismuth can cause false-negative results. Stool tests can also be used to confirm eradication, but no sooner than 4 weeks after completion of therapy.

Hepatitis Serology Hepatitis A virus (HAV), hepatitis B virus (HBV), and less often hepatitis C virus (HCV) are the usual causes of acute viral hepatitis. A person with symptoms of acute hepatitis should have these four hepatitis serologies performed: immunoglobulin M (IgM) anti-HAV, hepatitis B surface antigen (HBsAg), IgM anti-HBc, and anti-HCV. At present, stool and blood assays for HAV antigen are not available. The diagnosis of hepatitis A is made by the detection of IgM anti-HAV during acute illness. A positive anti-HAV with only IgG antiHAV indicates previous infection. In hepatitis B, HBsAg is the earliest serologic marker of infection and is present before elevation of the aminotransferases. If HBsAg is present for more than 6 months, the patient should be considered chronically infected (carrier). Antibodies to HBsAg (anti-HBs) indicate immunity to hepatitis B and appear several weeks to months after HBsAg disappears. The gap between the presence of HBsAg and anti-HBs is a window period; during this time antibody to hepatitis core antigen (anti-HBc) can be detected in the blood. AntiHBc can be differentiated into an IgM anti-HBc, which indicates recent infection, and an IgG anti-HBc, which indicates


previous infection. HBeAg, a subparticle of core antigen, is present only when HBsAg is present and is a marker for infectiousness. Anti-HBe appears after HBeAg disappears, indicates decreasing infectivity, a good prognosis, and remains detectable for years. HBV DNA testing can be used to follow titers in patients receiving antiviral therapy for chronic hepatitis B infection. Hepatitis delta virus (HDV) infection coexists with hepatitis B in about 4% of hepatitis B infections and carries an increased mortality rate. HDV depends on the presence of HBV for expression and replication and can cause acute or chronic infection. Previous vaccination for hepatitis B should produce a positive titer only for anti-HBs. Hepatitis C occasionally presents as acute hepatitis, but more frequently is detected in the evaluation of patients with elevated aminotransferases or chronic liver disease. With chronic hepatitis, aminotransferases are often only mildly elevated and occasionally, normal. The diagnosis is made by detecting antibody to hepatitis C (anti-HCV). Anti-HCV does not differentiate acute from chronic infection and does not indicate immunity. In acute hepatitis C the antibody may not be detected initially, and the test may need to be repeated later to confirm infection. In a patient with abnormal liver enzymes and a risk factor for hepatitis C (e.g., injection drug use, hemophilia, history of blood transfusions before 1985), a positive anti-HCV is sufficient to make the diagnosis. A quantitative HCV-RNA assay can be used for diagnosis of acute infection as early as 1 to 2 weeks after exposure, and before anti-HCV appears. Quantification of viral ribonucleic acid (RNA) by the reverse-transcriptase polymerase chain reaction (RT-PCR) also can confirm hepatitis C infection, as well as measure viral load. These tests are particularly useful in the absence of risk factors or abnormal liver enzymes, when antibody testing is indeterminate, or with immunodeficiency. In addition, quantification of viral RNA can assess response to treatment.

Human Immunodeficiency Virus The diagnosis of HIV infection usually depends on the detection of antibodies to the virus. The recommended screening test for HIV infection is an initial enzyme immunoassay, the ELISA test, which can detect the presence of antibody to HIV 2 to 8 weeks after infection. HIV ELISA testing studies in blood donors have found specificities of 99.7% and 99.99% (Chou et al., 2005). An initially positive ELISA should be repeated, and repeatedly positive ELISAs need to be confirmed by a more specific test, most often the Western blot. A positive ELISA combined with a negative Western blot should be considered a false-positive HIV test and indicates that HIV infection is not present. A positive ELISA and an indeterminate Western blot result can be a marker for early HIV infection or advanced acquired immunodeficiency syndrome (AIDS), or it can be a false-positive test result. The predictive value of a positive HIV test depends on the prevalence in the population being tested. Rapid HIV tests are currently available that check saliva, whole blood, and plasma. The whole-blood tests measure capillary blood with a finger stick and do not require centrifugation. These tests are interpreted visually, do not require instrumentation, and provide test results in minutes. Rapid tests may be preferred for testing in patients who are not likely to return for results of standard testing, for pregnant women at delivery with

no HIV testing during their pregnancy, and for testing during occupational exposure. Rapid tests for HIV have similar sensitivity and specificity to the standard ELISA tests. Clusters of false-positive oral rapid tests have been reported, emphasizing the need for confirmatory testing of positive rapid tests. Tests to measure HIV directly include quantitative HIV RNA testing by PCR, which measures viral load or actual viral replication. Quantitative HIV RNA measurements are useful in evaluating indeterminate Western blot results and acute HIV infection, when the patient presents before seroconversion. Because neonates born to HIV-infected mothers often have maternal antibodies for months, early testing with HIV-1 DNA PCR can identify infants with HIV infection. In 2006 the U.S. Centers for Disease Control and Prevention (CDC) recommended routine, voluntary HIV screening for all patients age 13 to 64 in any health care setting.

Iron Studies Iron deficiency is the most common type of anemia worldwide and therefore a significant cause of human morbidity. Other than menstrual blood losses, negligible iron is lost in a healthy person. Normally, regulation of iron absorption in the proximal small intestine controls iron balance. Iron deficiency results from increased need (growth of infancy or childhood, pregnancy), excessive loss (menstruation, hemorrhage, GI loss), inadequate intake (iron-deficient diet), or defective absorption (gastrectomy or sprue). In adult men or postmenopausal women with adequate iron stores, it takes 3 to 4 years for these stores to be depleted once negative iron balance starts. During early iron deficiency anemia, the erythrocytes may be normochromic normocytic, and later the peripheral blood smear may show microcytosis, anisocytosis, poikilocytosis, and hypochromia. The reticulocyte count is low, and RDW is high (>16). Bone marrow stores of iron are decreased or absent. Serum iron has marked diurnal variation (higher in morning, lower later in day) and is increased transiently after meals. Because morning levels determine the reference range, iron levels should be performed on a fasting morning specimen. Obtaining a serum iron level without determining the level of transferrin (total iron-binding capacity, TIBC) is of limited value. Serum iron is decreased with inflammation, infection, and ascorbate deficiency and increased with iron ingestion, transfusions, liver disease, aplastic anemia, and ineffective erythropoiesis. TIBC is an approximation of transferrin and can be calculated when the transferrin is known, as follows: TIBC( g / dL) = Transferrin(mg / dL) × 1.25

The total iron-binding capacity or transferrin is not subject to diurnal fluctuation, but it is reduced in chronic inflammation and malnutrition. Iron deficiency is the only microcytic hypochromic anemia associated with absent iron stores (Brittenham, 2005). The serum ferritin is the best indirect marker for the assessment of iron stores. However, serum ferritin is an acute-phase reactant and can be elevated in some patients with liver disease, malignancy, or inflammatory or infectious diseases. Therefore, although a low ferritin (1:320) of IgG to VCA; positive early antigen antibody (anti-EA); and initial absence of antibody to Epstein-Barr nuclear antigens (EBNAs). The most useful EBV-specific antibody to diagnose acute mononucleosis is the IgM VCA, which appears soon after the onset of symptoms and has sensitivity of 91% to 98%

Table 15-18 Effects of Drugs on Lipid Values

Drug

Total Cholesterol

LDL Cholesterol

HDL Cholesterol

Triglycerides

Androgens

—

↑

↓

—

Antiepileptics

—

↑

↑

↑

Thiazide diuretics

↑/—

↑

—

↑

Beta blockers

—

—

↓

↑

Alpha blockers

↓/—

↓/—

↑

↓

Corticosteroids

↑

↑

↑

↑

Cyclosporine

↑

↑

—

—

C-19 Progestin

—

↑

↓

—

C-21 Progestin

—

—

↓

—

Oral estrogens

↓

↓

↑

↑

Phenothiazines

↑

—

↓

↑

Retinoids

↑

↑

↓

↑

Modified from Henkin Y, Como JA, Oberman A. Secondary dyslipidemia: inadvertent effects of drugs in clinical practice. JAMA 1992;267:961-968. HDL, High-density lipoprotein; LDL, low-density lipoprotein.

195

15


Table 15-19 Causes of Magnesium Abnormalities

Hypermagnesemia Overingestion (usually in setting of renal insufficiency) Antacids Cathartics Laxatives Renal insufficiency Addison’s disease Hypothyroidism Lithium intoxication

Hypomagnesemia Gastrointestinal causes Low-magnesium diet Malabsorption Diarrhea Renal tubular disorders Ketoacidosis Alcohol abuse Drugs Diuretics Digitalis Cyclosporine

Natriuretic Peptides (BNP and N-terminal pro-BNP) Blood levels of natriuretic peptides are used in the evaluation of heart failure. Cardiac cells release natriuretic peptides, in response to stretch and wall tension. Ventricular myocytes release a pro–B-type natriuretic peptide (pro-BNP), which is cleaved into the active B-type natriuretic peptide (BNP) and the inactive N-terminal pro-BNP (NT–pro-BNP). Levels of both BNP and NT–pro-BNP increase with age and in renal insufficiency and are reduced in women and obese patients. Some medications, including spironolactone, ACE inhibitors, and angiotensin receptor blockers, lower BNP/NT– pro-BNP levels. Other conditions that increase natriuretic peptides include myocardial ischemia, atrial fibrillation, pulmonary embolus, pulmonary hypertension, chronic kidney disease, and sepsis. The major established use of BNP testing is evaluating acute dyspnea, when the cause is uncertain, to differentiate whether the etiology is from heart failure versus another cause. A normal level in a patient with acute dyspnea has a high negative predictive value and suggests that heart failure is unlikely the etiology. Elevated levels of BNP and NT–proBNP also are predictive of death or increased cardiovascular events. The optimal cutoffs for BNP/NT–pro-BNP vary with age. BNP less than 100 pg/mL or NT–pro-BNP less than 400 pg/mL makes the diagnosis of heart failure unlikely. Levels of BNP greater than 400 pg/mL or NT–pro-BNP greater than 2000 suggest heart failure (Dickstein et al., 2008). Using BNP measures to guide therapy in patients with established heart failure did not improve overall survival, quality of life, or total hospitalization but did reduce hospitalizations for heart failure in patients less than 75 years old (Pfisterer et al., 2009).

Cisplatin

Phosphorus

Aminoglycosides

The usual serum phosphorus level is approximately 2.5 to 4.8 mg/dL in adults and 4.0 to 6.0 mg/dL in children. Disorders of phosphorus metabolism are caused by variations in dietary intake, phosphorus excretion, and transcellular shifts. Because postprandial phosphorylation of glucose can decrease serum phosphorus levels, fasting specimens are more accurate. Hyperphosphatemia most often occurs in the setting of reduced renal excretion from renal insufficiency. Other causes of hyperphosphatemia include excess phosphate ingestion, either orally or with phosphate-containing enemas, hypoparathyroidism, and spurious causes such as thrombocytosis. Less common causes include acromegaly, hyperthyroidism, acidosis, and massive cell lysis from hemolysis, rhabdomyolysis, and tumor lysis after chemotherapy. Hypophosphatemia is defined as a serum phosphorus level below 2.5 mg/dL. Clinically significant hypophosphatemia occurs at levels less than 1.5 mg/dL. The three major mechanisms associated with hypophosphatemia are decreased intestinal absorption, increased phosphate loss from the kidney, and increased phosphorus shift into the bones. Decreased absorption occurs most often with antacid use. Persistent hypophosphatemia most frequently results from disorders causing increased phosphate loss in the kidney, including hyperparathyroidism, renal tubular disease, and chronic acidosis. Intracellular shifts into cells and bones,

Carbenicillin Amphotericin B

and specificity of 99%. Convalescent testing should document the appearance of IgG EBNA and disappearance of IgM VCA and anti-EA. Syndromes mimicking infectious mononucleosis, but with negative heterophile antibodies, are considered heterophile-negative infectious mononucleosis. The most common syndromes are related to cytomegalovirus infection and toxoplasmosis. Occasionally, viral hepatitis, rubella, lymphoma, leukemia, and the drugs isoniazid and phenytoin can cause a mononucleosis-like syndrome. Because heterophile antibodies are not uniformly positive early in the disease, serial tests may often be needed weekly to confirm mononucleosis. Specific serologic tests for EBV are relatively expensive and take longer to obtain results, so they are generally reserved for unclear cases and are not necessary in most patients with infectious mononucleosis. In an adolescent or young adult with appropriate clinical symptoms, heterophile antibodies are 95% sensitive and specific. 196


during acute respiratory alkalosis, hyperalimentation, intravenous carbohydrate administration, rapid tumor growth, or treatment of respiratory failure or diabetic ketoacidosis, can cause hypophosphatemia.

Potassium Potassium is the most abundant cation in the body and has a much higher concentration in the intracellular space than in extracellular fluids. Normal potassium levels are maintained despite fluctuating potassium intake by adjustments in renal secretion of potassium. Hyperkalemia is defined as a serum potassium level greater than 5.1 mmol/L. Occasionally, hyperkalemia can be an artifact (pseudohyperkalemia) of phlebotomy, associated with thrombocytosis, leukocytosis, or hemolysis during phlebotomy. In a patient with hyperkalemia of no apparent cause, a plasma potassium level can eliminate these effects on the potassium measurement. Because the normal response to increased potassium intake is to increase excretion, hyperkalemia is not likely to be attributed to increased intake unless there is a deficiency in potassium excretion. Shifts of potassium from intracellular to extracellular fluids, such as with acute metabolic acidosis, crush injury, burns, insulin deficiency, beta-adrenergic blockade, and hemolysis, can be associated with a transient hyperkalemia. Persistent hyperkalemia is usually associated with decreased potassium excretion. Potassium excretion by the kidney is flow dependent; therefore, oliguria and anuria are important causes of hyperkalemia. Because aldosterone deficiency is an important cause of decreased potassium excretion, hyperkalemia is seen with hyporeninism, hypoaldosteronism, type 4 renal tubular acidosis, and drugs that inhibit aldosterone (Table 15-20). Hypokalemia is associated with a serum potassium level of less than 3.5 mmol/L. Symptoms are nonspecific and include muscular weakness. Occasionally, hypokalemia is associated with sustained inadequate potassium intake, particularly in patients with alcohol abuse. Transient episodes of hypokalemia are associated with increased extracellular to intracellular potassium shifts and occur with catecholamine increase, hyperinsulinemia, and adrenergic drugs such as bronchodilators. More frequently, hypokalemia is a result of GI loss of potassium, such as with protracted vomiting, diarrhea, and laxative abuse. Other causes of hypokalemia include drugs, metabolic alkalosis, skin losses, and increased urinary losses. Hypomagnesemia is an important cause of refractory hypokalemia.

Pregnancy Tests Current pregnancy tests use immunoassays with monoclonal antibodies to measure the beta subunit of human chorionic gonadotropin (hCG). Serum assays and sensitive urine assays can now detect pregnancy approximately 1 week after conception. Home pregnancy tests are generally sensitive enough to diagnose pregnancy accurately when done on the first day of the missed period. The most common reason for a false-negative pregnancy test is incorrect timing, such as performing the test too soon. In the first 4 to 8 weeks of pregnancy, hCG levels double approximately every 2 days. Failure to double in 48 to 72 hours suggests an ectopic pregnancy or abnormal intrauterine

pregnancy. For the first 2 weeks after conception, serum levels of hCG are higher than those in urine. However, beginning at approximately 3 weeks and for the remainder of the pregnancy, urine levels are higher than serum levels. Levels of hCG return to normal approximately 2 weeks after delivery. After an abortion, levels return to normal in approximately 3 to 8 weeks. Other conditions that can raise hCG levels include gestational trophoblastic neoplasms, such as hydatidiform mole and choriocarcinoma.

Prostate-Specific Antigen Prostate-specific antigen (PSA) is a glycoprotein protease enzyme produced by the epithelial cells of the prostate. This protein circulates in the serum and can become elevated because of benign and malignant conditions of the prostate. From 50% to 90% of PSA is protein bound and the remainder is free. PSA is used as a tumor maker for the screening, diagnosis, and management of prostate cancer. PSA lacks specificity for cancer, however, because it can be elevated in benign conditions such as benign prostatic hypertrophy (BPH). Estimates suggest that a PSA higher than 4 ng/mL has sensitivity of 70% to 80% and specificity of 60% to 70% for prostate cancer. Factors other than prostate cancer can affect the PSA level (Table 15-21). Controversy surrounds the effect of the digital rectal examination (DRE) on PSA. Theoretically, digitally palpating the prostate gland should elevate the serum PSA. However, it appears that PSA elevations after DRE are probably not significant, so there is no recommendation to withhold PSA testing immediately after DRE. Although elevations of the PSA are associated with increased risk of prostate cancer, the upper limit of normal of 4 ng/mL may be somewhat arbitrary. During an initial screening examination, prostate cancer was found in 27% of men with PSA levels of 4.1 to 9.9 ng/mL and 59% with PSA over 10 ng/mL (Hernandez and Thompson, 2004). However, prostate cancer is found in 23.9% of men with PSA of 2.1 to 3.0 ng/mL and 26.9% with PSA of 3.1 to 4.0 ng/mL (Thompson et al., 2004). The positive predictive value (PPV) of the PSA is improved if used complementary to DRE (Table 15-22). The PPV is doubled if the patient also has an abnormal DRE. A normal PSA does not exclude cancer; 20% to 40% of men with organ-confined prostate cancer will have PSA within the reference range. One report of men with confirmed, untreated, clinically significant prostate cancer found these PSA values: less than 4 ng/mL (27%), 4 to 10 ng/mL (21%), 10 to 20 ng/ mL (16%), and greater than 20 ng/mL (36%). The use of PSA for screening for prostate cancer remains controversial. Although it is clear that PSA testing can lead to earlier detection of prostate cancer, it is not clear that early diagnosis and treatment offers significant reduction in prostate cancer mortality. Given that the lifetime risk of death from prostate cancer is only 3% in U.S. men, a large portion of men detected by screening may not have clinically significant disease. In addition to screening, PSA is used to monitor the response to treatment for localized prostate cancer. After radical prostatectomy, PSA levels should become undetectable. Any detectable levels suggest residual or recurrent tumor and may occur months or years before it becomes clinically apparent. PSA levels fall after radiation therapy, although usually do not become 197

15


Table 15-20 Causes of Abnormal Potassium Levels

Hyperkalemia

Renal losses

Pseudohyperkalemia

Diuresis

Thrombocytosis

Renal tubular acidosis (proximal, distal)

Leukocytosis

Hypomagnesemia

Prolonged tourniquet use during venipuncture

Hyperaldosteronism

Hemolysis

Cushing’s syndrome

Reduced excretion

Nonrenal losses

Oliguria

Diarrhea

Renal failure

Vomiting

Hyporeninemic hypoaldosteronism

Periodic paralysis

Adrenal insufficiency

Burns

Type IV renal tubular acidosis

Cellular shifts

Cellular shifts

Alkalosis

Acute acidosis

Beta-adrenergic therapy

Insulin deficiency

Catecholamine excess

Rhabdomyolysis

Drugs

Drugs

Thiazide diuretics

Beta blockers

Loop diuretics

ACE inhibitors

Epinephrine

Angiotensin receptor blockers

Albuterol

Spironolactone

Carbenicillin

Triamterene

Ticarcillin

Amiloride

Licorice

NSAIDs

Glucocorticoids

Heparin

Mineralocorticoids

Cyclosporine Pentamidine

Hypokalemia Inadequate diet Malnutrition Alcoholism ACE, Angiotensin-converting enzyme; NSAIDs, nonsteroidal anti-inflammatory drugs.

undetectable. A PSA recurrence has been defined as three successive increases in the PSA level after radiation therapy.

Total Protein Total protein includes albumin and globulin. The factors that affect the total protein level include changes in fluid status, the balance of protein synthesis and catabolism, and protein 198

losses. While dehydration can cause a relative increase in serum protein concentration, volume expansion causes a relative decrease in protein concentration. Elevated protein levels in the absence of dehydration are usually related to increased globulin levels. As previously discussed, acute-phase reactants are proteins that are increased in inflammatory conditions and include C-reactive protein, haptoglobin, fibrinogen, ceruloplasmin, and α1-antitrypsin.


Table 15-21 Noncancer Factors that May Influence ProstateSpecific Antigen

Table 15-22 Positive Predictive Value (PPV) of Total ProstateSpecific Antigen (PSA) for Prostate Cancer

Factor

Change

Acute urinary retention

Increase

Digital Rectal Examination

Androgens

Increase

Antiandrogens

Decrease

Negative

Bed rest

Decrease

Positive

Benign prostatic hypertrophy

Increase

Cirrhosis

Increase

Data from Oesterling JE. Prostate-specific antigen: a valuable clinical tool. Oncology 1991;5:112.

Cystoscopy

Increase

Digital rectal examination

Not significant

Diurnal variation

No change

Ejaculation

Increase

Extensive exercise

Increase

Finasteride

Decrease

Physiologic variation

May fluctuate by 30%

Prostate needle biopsy

Increase

Prostatic massage

Increase

Prostatitis

Increase

Radial prostatectomy

Decrease

Radiation therapy

Increase initially then decrease

Transurethral resection of prostrate

Increase

Transurethral ultrasound of prostrate

No change

Urethral instrumentation

Increase

Serum protein electrophoresis separates proteins based on their mobility in an electric field and can provide a visual estimate of albumin and globin levels. The five bands on the electrophoresis column include albumin, α1-globulin, α2-globulin, β-globulin, and γ-globulin. The main component of the α1 band is α1-antitrypsin, which may increase with pregnancy, estrogen therapy, and inflammation. α2Globulin is composed of haptoglobin, ceruloplasmin, and α2-macroglobulin. The main component of β-globulin is transferrin, which functions to transport iron. Transferrin levels are reduced in liver disease, nephrotic syndrome, protein-losing enteropathy, and starvation. Levels of transferrin are helpful in monitoring nutritional status in hospitalized patients. Elevations may be seen in iron deficiency anemia, pregnancy, and estrogen use. The β-lipoprotein band can be found in the α2-globulin or β-globulin zone. The immunoglobulins are found primarily in the γ region. Diffuse elevations in the γ region can occur with chronic infections, liver disease, autoimmune disorders, and granulomatous diseases. A monoclonal spike in the γ region indicates proliferation of a single immunoglobulin, as

PSA Value 0.0-4.0 ng/mL

4.1-10 ng/mL

>10 ng/mL

9%

20%

31%

17%

45%

77%

seen in myeloma or a monoclonal gammopathy of uncertain significance. Immunoglobulin abnormalities noted on protein electrophoresis can be further characterized by immunoelectrophoresis.

Rheumatoid Factor and Anti–Cyclic Citrullinated Peptide Antibodies The diagnosis of rheumatoid arthritis (RA) is usually made based on clinical findings, supported by laboratory testing. The mainstay of testing has been the IgM rheumatoid factor (RF), which is an autoantibody directed against the Fc portion of the IgG molecule. The sensitivity of RF is approximately 54% to 88% and the specificity 48% to 92%, depending on the method used (Lee and Schur, 2003). RF is not specific for RA and may be detected in the serum of persons with other rheumatoid conditions, chronic infections, or inflammatory conditions, as well as in healthy older adults. Results are usually reported as a titer determined by using a tube dilution method. A significant titer is 1:80 or greater. In RA, titers are often 1:640 to 1:520 but can even be found up to 1:320,000. Very high titers more likely indicate severe disease or systemic involvement. Increasing serial titer elevations can be used to monitor RA disease progression, but not response to therapy. RF titers may decrease during remission, but only rarely do they become undetectable. The ESR is a better index of disease activity. Anti–cyclic citrullinated peptide (anti-CCP) antibodies show promise in the diagnosis of RA. Citrulline is an amino acid produced by modification of arginine and is found in filaggrin, a component of keratin. Recently, sensitivity and specificity of anti-CCP antibodies was reported as 67% and 95%, respectively. The advantage of anti-CCP over RF is that it is much more specific for RA. Its optimal use is uncertain, but anti-CCP testing shows greatest benefit with false-positive RF, such as in hepatitis C with cryoglobulinemia. In patients with a moderate pretest probability of RA, positive anti-CCP significantly increases the likelihood of RA (Shmerling, 2009).

Sodium Abnormal serum sodium levels are markers for impaired water balance. The reference range for serum sodium concentration is 135 to 145 mmol/L. In the evaluation of abnormal 199

15


Table 15-23 Classification of Hyponatremia

Clinical Findings

Causes

Volume depletion Tachycardia Hypotension Urine sodium serum osmolality Normal thyroid and adrenal function

CNS disorders: infection, mass lesion, head trauma, acute intermittent porphyria Pulmonary: lung cancer, infection Drugs: chlorpropamide, opiates, nicotine, diuretics, phenothiazines, vincristine, carbamazepine, SSRIs

Psychogenic polydipsia CNS, Central nervous system; SSRIs, selective serotonin reuptake inhibitors.

Table 15-24 Classification of Hypernatremia

Total Body Sodium (Na)

Causes

Urine Measurements

Reduced total body sodium (both Na and water losses, but relatively more loss of water)

Gastrointestinal losses: diarrhea, lactulose Skin losses: excess sweating Renal losses: loop diuretics, osmotic diuretics

Urine Na 20 mEq/L Hypertonic or isotonic urine

Modified from Schrier RW. Renal and Electrolyte Disorders, 4th ed. Boston, Little, Brown, 1992, p 43.

sodium levels, it is helpful to measure or calculate the plasma osmolarity, which typically has a range of 280 to 295 mOsm/ kg H2O. Calculated osmolarity = (2 × Na) + (BUN / 2.8) + (Glucose / 18)

In most cases, hyponatremia is associated with hypo-osmolality. Pseudohyponatremia can occur in the presence of other osmotically active substances, such as ethanol, methanol, mannitol, and glucose. Pseudohyponatremia is associated with an osmolar gap, which means the laboratory’s measured osmolarity is greater than the calculated osmolarity by 10. In the setting of hyperglycemia, every 100-mg/dL rise in glucose lowers serum sodium by 1.6 mmol/L. In hyponatremia associated with hypo-osmolarity, the determination of the patient’s volume status is essential to determine the cause of hyponatremia (Verbalis, 2007). 200

Hyponatremia can occur in states of volume deficiency, euvolemic states, or hypervolemic conditions (Table 15-23). The clinical significance of hyponatremia depends on the severity and rate of development. In general, symptoms are seen when sodium levels are less than 120 mmol/L. Hypovolemic hyponatremia is associated with low total-body sodium. The most common sources of sodium loss are the GI tract or kidney and, less often, third-space losses. With nonrenal losses, the kidney responds by reducing sodium and water excretion in the urine. In the absence of diuretic therapy, the urine sodium concentration is usually less than 30 mmol/L, and urine osmolarity is high. Hypovolemic hyponatremia responds readily to isotonic fluid replacement. Hypervolemic hyponatremia can occur with advanced congestive heart failure, cirrhosis, nephrotic syndrome, and renal failure in the presence of total-body sodium overload and edema. In these disorders, effective renal blood flow is reduced, thus stimulating the release of antidiuretic hormone


Table 15-25 Causes of Hyperuricemia*

Overproduction Myeloproliferative disorders Polycythemia vera Hemolytic anemia Malignancies Psoriasis Toxemia of pregnancy Ethanol

Decreased Excretion Renal failure Volume depletion Hypothyroidism Hyperparathyroidism Diabetic ketoacidosis

Drugs Thiazides Furosemide Aspirin (low dose) Ethambutol Pyrazinamide Cyclosporine Niacin Vitamin B12 therapy *Normal

range: 3.5 to 5.1 mmol/L.

levels are not helpful because most causes of hyponatremia are associated with elevated ADH levels. The major causes of SIADH are drugs and pulmonary and central nervous system diseases. SIADH can respond to fluid restriction or correction of the underlying disorder. Another cause of euvolemic hyponatremia is called primary polydipsia, which occurs in people who consume massive amounts of water and have very large volumes of urine. In general, plasma osmolarity is mildly decreased. These individuals have low urine sodium and dilute urine. The hyponatremia readily responds to a reduction in fluid intake. Hypernatremia is a serious electrolyte abnormality, but it generally occurs in the setting of a significant underlying medical illness (Table 15-24). Determination of the patient’s volume status is also critical in the evaluation of hypernatremia (Schrier, 1992). Hypernatremia can occur in the setting of reduced total-body sodium, normal total-body sodium, and increased total-body sodium. Hypernatremia is seen with reduced total-body sodium when sodium and water losses occur but more water than sodium is lost. For example, when a patient has significant diarrhea, hypernatremia can develop when the patient cannot ingest enough water to compensate for the loss. Clinical evidence of dehydration is noted, urine osmolarity is high, and the urine sodium level is low. Water loss not connected with sodium loss is associated with hypernatremia and normal total-body sodium. Inadequate ADH secretion (central diabetes insipidus) or renal tubules unresponsive to ADH (nephrogenic diabetes insipidus) can lead to hypernatremia because of an inability to concentrate the urine. Uncommon disorders of the hypothalamus and pituitary can cause a high-set osmoreceptor in which osmotic, but not volume, regulation is impaired. The trigger for the release of ADH may be closer to 300 instead of the normal 285 mOsm/kg. Less frequently, hypernatremia can occur in a setting of increased total-body sodium from an excessive exogenous sodium load. Hypertonic intravenous fluids, saltwater neardrowning, and hypertonic dialysis can cause hypernatremia.

Streptococcal Testing (ADH), which reduces renal excretion of water. Both sodium and water are increased, but water is increased proportionally more than sodium. In the absence of diuretic therapy, urine sodium is generally less than 30 mmol/L, and urine osmolarity is increased. The most common cause of euvolemic hyponatremia is the syndrome of inappropriate ADH secretion (SIADH), which occurs when the stimulus for ADH secretion is not related to osmolarity or reduced renal blood flow. No edema is present, although mild volume expansion and a modest increase in weight are seen. Continued release of ADH occurs despite low plasma osmolarity. SIADH should be considered a cause of hyponatremia in the absence of evidence of volume loss, edema, and adrenal insufficiency or hypothyroidism. The major laboratory finding, in addition to hyponatremia, is urine that is not maximally dilute (i.e., urine osmolarity >100 mOsm/kg H2O). The urine sodium level is greater than 30 mmol/L, assuming adequate sodium intake. Other clinical findings that suggest SIADH include a uric acid level less than 3 mEq/dL and BUN less than 10 mg/dL. Serum ADH

“Pharyngitis” is a frequent office diagnosis, but the only common form of pharyngitis that requires antibiotic treatment is that caused by group A beta-hemolytic streptococci (GABHS). Approximately 15% to 30% of children and 5% to 10% of adults with sore throat have streptococcal pharyngitis. Suggestive clinical features include fever, no cough or rhinorrhea, tonsillar exudates or beefy-red pharynx, and tender anterior cervical lymphadenopathy. For an acutely ill patient, the rapid antigen detection test (RADT) and traditional bacterial throat culture are available to identify GABHS. In the setting of pharyngitis and a typical syndrome, a positive culture or RADT is sufficient to begin treatment. The sensitivity of both is affected by throat swab technique. Using Dacron or rayon rather than cotton swabs will enhance the chances of detection. Testing should be done of both tonsils or tonsillar pillars and the posterior pharynx. Antigen or bacterial recovery from the throat is increased by rigorous swabbing. Avoid swabbing just the soft palate, tongue, buccal mucosa, or lips. The RADT has the advantage of giving immediate results, which allows for 201

15


early antibiotic therapy and thus decreases the duration of illness, complications, and contagiousness. Current RADTs use immunoassay or nucleic acid testing to detect the group A streptococcal carbohydrate. This antigen disappears rapidly after antibiotic therapy, so a history of recent antibiotic use may give a false-negative result. The major limitation of rapid streptococcal tests is low sensitivity (75%-80% on average), but specificity is high (95%-98%). Therefore, a positive test can be accepted as evidence of disease and therapy begun without further testing. However, a negative result does not exclude the possibility of GABHS as the source of the pharyngitis. Children and adolescents with a negative RADT should have a throat culture for confirmation. Because of the low incidence of streptococcal pharyngitis and the extremely low risk of rheumatic fever in adults, the American Society of Infectious Diseases supports the use of RADT alone in adults, without confirmation by cultures (Bisno et al., 2002). The throat culture is performed on sheep blood agar plate under aerobic conditions. If proper collection and plating technique are used, throat culture sensitivity is 95% to 96% and specificity 99.5%. With poor technique, sensitivity can be as low as 30%. To differentiate group A from other streptococci, a bacitracin disk is placed on this agar. Hemolysis is inhibited in over 95% of group A streptococci by bacitracin, whereas only 10% to 20% of groups C and G and a small percentage of group B are inhibited by bacitracin. Previous antibiotic use may diminish the colony count. If clinical conditions suggest the presence of other pharyngeal pathogens, such as Candida albicans, Corynebacterium diphtheriae, or Neisseria gonorrhoeae, the laboratory test should be altered because different collection and plating techniques are required. Throat culture results are generally reported 24 to 28 hours after plating. Antibiotic sensitivities are not routinely reported because GABHS is uniformly sensitive to penicillin.

become negative within 1 year. A fourfold decline in titer 6 months after treatment suggests an adequate response to treatment of primary or secondary syphilis. A fourfold rise in titers after treatment suggests reinfection. Low titers may persist after treatment of late and latent syphilis. Approximately 20% of nontreponemal screening tests are false positive; false-positive tests usually have titers less than 1:8. Causes of false-positive nontreponemal tests include autoimmune disorders, HIV infection, infectious mononucleosis, endocarditis, and lymphoma. The treponemal tests, such as the fluorescent treponemal antibody absorption (FTA-ABS) test or T. pallidum enzyme immunoassay (EIA), are used to confirm infection in a patient with a positive nontreponemal test. The FTA has a sensitivity of 84% in primary syphilis and almost 100% in other stages of syphilis. The specificity is 96%; approximately 1% of the population has a false-positive treponemal antibody, and it is not routinely used for screening. The treponemal tests are reported as positive or negative. Treponemal tests remain positive in 95% of patients, even after treatment, and are not used to monitor treatment response. In neurosyphilis, cerebrospinal fluid (CSF) abnormalities include elevated protein, a lymphocytic pleocytosis, and a positive VDRL. The CSF VDRL is the preferred test because it is more specific than the CSF FTA. However, the sensitivity is low enough that a negative CSF VDRL does not rule out neurosyphilis. In congenital syphilis, the diagnosis can be difficult because both FTA and VDRL antibodies can be transferred passively to newborns, and their identification at birth in the baby does not necessarily indicate infection. Passively transmitted antibodies generally decline in the first 2 months of life. If titers rise after birth, congenital syphilis is likely. Testing using specific T. pallidum EIA IgM may allow earlier diagnosis of congenital syphilis.

Syphilis Testing

Thyroid Testing

The sexually transmitted disease (STD) syphilis is usually diagnosed with serologic testing. Although darkfield microscopy can identify spirochetes in fluid obtained from lesions of primary syphilis, the test has many false-negative readings, and many physicians are not trained to perform these tests. PCR for Treponema pallidum DNA is now commercially available for diagnosing early syphilis, with early reports showing good sensitivity and specificity. The major serologic tests for syphilis are the nonspecific nontreponemal Venereal Disease Research Laboratories (VDRL) and rapid plasma reagin (RPR) tests, which measure antibody production to a cardiolipin-cholesterol-lecithin antigen, and the specific treponemal antibody tests, which measure antibodies against the spirochete T. pallidum. The usual screening for syphilis is a two-step process, beginning with the RPR or VDRL test, followed by treponemal antibody testing for confirmation. The RPR or VDRL is reported as a titer of the highest dilution giving a positive test. The VDRL usually becomes positive approximately 1 to 4 weeks after the development of a chancre. The highest titers of nontreponemal tests are seen in secondary syphilis. The sensitivity of the RPR or VDRL is 78% to 86% in primary syphilis, 100% in secondary syphilis, and 95% to 98% in latent syphilis. Titers of VDRL or RPR parallel disease activity. After appropriate treatment of primary or secondary syphilis, titers decline and usually

Currently available tests for assessing thyroid function measure functional activity of the thyroid, the hypothalamicpituitary-thyroid axis, or thyroid hormone levels. The third-generation thyroid-stimulating hormone (TSH) test is the best method to confirm or exclude thyroid disease in an ambulatory population. TSH is produced by the pituitary and is inhibited by circulating thyroxine (T4) and triiodothyronine (T3). In general, a normal TSH level is approximately 0.5 to 5 mIU/L and excludes hyperthyroidism or primary hypothyroidism. Supersensitive tests measure TSH at levels at least as low as 0.01 mIU/L. TSH levels less than 0.1 mIU/L suggest hyperthyroidism. Levels of 0.1 to 0.5 mIU/L may represent subclinical hyperthyroidism or excess thyroid hormone administration. Levels of 6 to 10 mIU/L are often considered subclinical hypothyroidism, are usually associated with normal free T4 levels, and are not usually associated with symptoms. In patients with subclinical hypothyroidism, the presence of thyroid antibodies suggests a risk of conversion to frank hypothyroidism of about 5% per year. Symptomatic hypothyroidism occurs with TSH levels greater than 10 mIU/L. The TSH test is also the best way to monitor the results of replacement or suppressive therapy. Although the TSH level is an excellent screen for thyroid function in ambulatory patients, it must be interpreted with caution in acutely ill patients. TSH levels should be used to diagnose

202


thyroid disorders in acutely ill hospitalized patients only when less than 0.1 mIU/L or greater than 20 mIU/L. Measurements of circulating thyroid hormone should be obtained to confirm abnormal TSH levels. Measurement of free T4 levels measure the total amount of hormone in blood, free and protein bound. Total T4 or T3 levels can be misleading in the setting of protein-binding abnormalities, such as estrogen therapy and liver disease. An approximate reference range in the adult for free T4 is 0.7 to 2.5 ng/dL and for free T3 0.2 to 0.5 ng/dL. Free T3 testing is usually not necessary. One exception is in early hyperthyroidism, when the TSH is suppressed, free T4 is normal, and free T3 is elevated. Primary hypothyroidism accounts for more than 95% of cases of hypothyroidism and is associated with an elevated TSH and reduced free T4. Central hypothyroidism (secondary or tertiary) is associated with low free T4 and normal to low TSH. Primary hyperthyroidism is associated with a suppressed TSH and elevated free T4. Subclinical hyperthyroidism is associated with a reduced TSH, but normal free T4 and T3 levels. The radioactive iodine uptake scan measures 24-hour thyroid uptake of a labeled quantity of radioactive iodine. In normal persons, uptake is 8% to 30%. Lower limits of normal cannot be reliably differentiated from hypothyroidism in the radioactive iodine uptake scan. Its major value is to help identify causes of thyrotoxicosis associated with low levels of iodine uptake, such as thyroiditis and fictitious hyperthyroidism from overingestion of thyroid hormones. Other causes of reduced thyroid hormone uptake include recent iodine contrast administration and amiodarone.

Uric Acid Uric acid is produced in the liver as a byproduct of purine metabolism. Measurement of uric acid is useful in the evaluation of gout and monitoring of certain types of chemotherapy. Uric acid levels are increased in situations with increased dietary purine intake, reduced excretion, or increased production. In addition, volume status affects uric acid secretion. With a decrease in extracellular volume, uric acid excretion declines, and serum uric acid levels increase. Conversely, volume expansion increases uric acid excretion and leads to hypouricemia. Several drugs inhibit the reabsorption of uric acid in the kidney and therefore lead to uricosuria (Table 15-25). Progressively higher levels of hyperuricemia predict the likelihood of gout; however, most authorities believe that asymptomatic hyperuricemia should not be treated. At 37° C, saturation in plasma occurs when uric acid levels are greater than 6.8 mg/dL. Most patients with gout have uric acid levels greater than 7 mg/dL at some time, but they can have normal serum uric acid levels at the time of an acute gouty attack. Although a biologically significant uric acid level is greater than 6.8 mg/dL, the upper limits of “normal” based on population studies are 7.7 mg/dL for men and 6.8 mg/dL for women. The incidence of gout is approximately 5% per year in men with uric acid levels greater than 9 mg/ dL, but only 0.5% per year with uric acid levels of 7.0 to 8.9 mg/dL. A distinction between production of uric acid and reduced uric acid excretion as a cause of hyperuricemia may be helpful in evaluating patients with gout. This can

be accomplished by measurement of 24-hour urinary uric acid and creatinine excretion. “Underexcretion” is identified when the fractional excretion (excretion of uric acid/ excretion of creatinine) is less than 6%. When a person is consuming a regular diet, excretion of uric acid greater than 800 mg/day is considered hyperuricosuria. Follow-up testing for patients with hyperuricosuria can be repeated on a lowpurine diet, with 24-hour excretion of uric acid greater than 600 mg indicating uric acid overproduction. Of patients with gout, an estimated 90% have reduced uric acid excretion, and less than 10% have overproduction of uric acid as the cause. Drugs that lower serum uric acid include losartan, amlodipine, fenofibrate, and atorvastatin.

Urine Drug Screens The standard urine drug screen in a clinical setting is a panel of immunoassays designed to detect common drugs of abuse. The panel can include the five drugs required by federal workplace testing: amphetamines, cocaine, opiates, marijuana, and PCP. Other drugs that are prevalent in the community can be added to the panel, including benzodiazepines and barbiturates. Point-of-care testing kits can be ordered for office use that are individualized to the need of the practice. These point-of-care tests provide results in minutes and have generally good sensitivity. The manufacturers recommend follow-up testing with a different laboratory technique to confirm positive tests. The guidelines that mandate testing procedures for federal workplace testing do not apply in clinical settings. For example, there are no required chain-of-custody policies to safeguard the processing of specimens in clinical settings. Clinical laboratories are not required to perform tests to ensure that the urine sample provided has not been diluted or adulterated. The cutoff points designated to define a positive and negative test are somewhat arbitrary, are chosen mainly to maximize sensitivity and specificity, and do not correlate with the degree of impairment or toxicity. Urine that contains a drug concentration below the cutoff will be reported as negative, even though the drug is present. With standard drug screens, the immunoassays can produce falsepositive results. In workplace settings, positive screening tests are followed by more specific tests, such as gas chromatography/mass spectroscopy (GC/MS), and a specimen is not reported as positive unless the GC/MS is also positive. In clinical settings, confirmatory tests are not routinely available and are rarely ordered. Therefore, urine drug screens are designed to help the physician take care of the patient; they are not intended to be used for forensic or legal purposes. Generally, drugs and their metabolites are detectable in urine tests for about 3 days after use. A notable exception is marijuana, which can be present in the urine for weeks after heavy use. Urine drug screens have significant limitations, which are not always recognized. For example, most immunoassays for “opiates” are designed to detect heroin and measure codeine, which is a byproduct of heroin and morphine metabolism. However, synthetic opioids such as fentanyl or methadone do not cross-react with codeine immunoassays and will produce a negative result. A negative urine drug screen for opiates might falsely lead the physician to believe that the person does not use any opioids. To help determine the sensitivity and the known false-positive results associated 203

15


with a urine drug screen, the physician should review the package inserts (Warner and Sharma, 2009).

Vitamin D Vitamin D is now recognized not only for its importance in preventing rickets, but also in preventing osteopenia, osteoporosis, muscle weakness, and falls. Testing levels of vitamin D can be considered in patients at increased risk of vitamin D deficiency, including elderly patients and those with osteoporosis, osteopenia, fat malabsorption, chronic kidney disease, and increased skin pigmentation. The term “vitamin D” includes vitamin D2 and vitamin D3. Vitamin D2 (calciferol) is manufactured from the plant sterols in yeast, and vitamin D3 (cholecalciferol) is manufactured from lanolin. Vitamin D is hydroxylated by the liver into 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D in the body. The kidney converts 25(OH)D into 1,25dihydroxyvitamin D [1,25(OH)2D], which is the active form of vitamin D.

The laboratory diagnosis of vitamin D deficiency relies on measuring the levels of 25(OH)D. Measuring 1,25(OH)2D is not recommended in clinical practice because it is not a reliable indicator of vitamin D status. 1,25(OH)2D has a half-life of only 4 hours, whereas 25(OH)D has a halflife of about 3 weeks. In addition, vitamin 1,25(OH)2D levels can actually increase with vitamin D deficiency, because increasing PTH levels result in increasing levels of 1,25(OH)2D. The 25(OH)D is a measurement of vitamin D intake and that made in the body after sun exposure. Although some laboratories may report 25(OH)D2 and 25(OH)D3 levels, it is the total level that is used clinically to monitor vitamin D status. PTH rises when the 25(OH)D levels are less than 30 ng/mL. Although labs may list 20 to 100 ng/mL as the reference range for 25(OH)D, most experts define a preferred level of 25(OH)D as 30 to 60 ng/mL, with deficiency defined as less than 20 ng/mL and insufficiency as 20 to 20 ng/mL. Currently, a 25(OH)D greater than 30 ng/mL is considered the preferred level for both adults and children.


Web Resources www.nlm.nih.gov/medlineplus/laboratorytests.html An overview for patients that explains basic laboratory principles, also gives links to other resources. www.labtestsonline.org/understanding/analytes/microalbumin/test.html Developed by American Association for Clinical Chemistry, site allows patients to search for explanation of specific tests.

204

www.ahrq.gov/CLINIC/uspstfix.htm Homepage of the U.S. Preventive Services Task Force (USPSTF), which lists recommendations for screening tests.

C H A P T ER

16

Infectious Diseases Anthony Zeimet, David R. McBride, Richard Basilan, William E. Roland, David McCrary, Hoonmo Koo

Chapter contents BRONCHITIS Chronic Bronchitis: Acute Exacerbation

208 209

Prostatitis

227

TICK-BORNE INFECTIONS

228

PNEUMONIA

209

INFLUENZA

210

Ehrlichiosis

228

SYSTEMIC VIRAL INFECTIONS

212

Babesiosis

230

Varicella and Herpes Zoster

213

Rocky Mountain Spotted Fever

228

Lyme Disease

230

Measles

214

Tularemia

230

Epstein-Barr Virus and Cytomegalovirus

214

Colorado Tick Fever

231

TUBERCULOSIS

215

Prevention of Tick-Borne Disease

231

CELLULITIS

231

Epidemiology Presentation Diagnosis Treatment Latent Tuberculosis Infection and Purified Protein Derivative Interferon-γ release Assays

SEXUALLY TRANSMITTED INFECTIONS Prevention Genital Ulcers Herpes Simplex Syphilis Chancroid Lymphogranuloma Venereum and Granuloma Inguinale

215 215 216 216 216 218

218 219 219 219 220 221 222

Urethritis and Cervicitis

222

Chlamydia trachomatis Neisseria gonorrhoeae Nongonococcal Urethritis Trichomonas vaginalis

222 223 223 223

Pelvic Inflammatory Disease

224

Human Papillomavirus

224

Ectoparasites

225

GENITOURINARY INFECTIONS

225

Urinary Tract Infection in Pregnancy

226

Catheter-Associated Urinary Tract Infection

227

Recurrent Urinary Tract Infection

224

Urinary Tract Infections in Children

227

©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10016-8

FURUNCLES AND CARBUNCLES

232

DIABETIC ULCERS

234

BITE INFECTIONS

235

Animal Bites

235

Human Bites

235

Treatment

237

BONE AND JOINT INFECTIONS

237

Osteomyelitis

Diabetic Foot Osteomyelitis

237

239

Orthopedic Hardware Infections

239

Septic Arthritis

240

FEVER OF UNKNOWN ORIGIN

240

COMPLICATED INTRA-ABDOMINAL INFECTIONS

242

SPONTANEOUS BACTERIAL PERITONITIS

242

CENTRAL NERVOUS SYSTEM INFECTIONS

243

Bacterial Meningitis

243

Viral Encephalitis

244

Brain Abscess

244

INFECTIOUS DIARRHEA

244

Viral Gastroenteritis

245

Travelers’ Diarrhea

246

Antibiotic-Associated Diarrhea

246

16

Infectious Diseases

BRONCHITIS David R. McBride Key Points • A cute bronchitis is part of the continuum of “acute respiratory tract infection” most often caused by viruses. • Antibiotics are not routinely recommended for the treatment of bronchitis. • The cough of bronchitis may last up to 4 weeks. • Beta-adrenergic agonists are not helpful unless patients have signs of bronchospasm associated with the infection. • Acute exacerbations of chronic bronchitis with increased sputum production should be treated with antibiotics to decrease mortality.

Infections of the upper respiratory tract accounted for more than 36 million ambulatory medical visits in 2005, according to the National Ambulatory Medical Care Survey (Cherry et al., 2007). Although a large percentage of these infections are viral in origin, antibiotics are still prescribed for more than 50% of patients with acute respiratory tract infection (ARTI). Acute bronchitis, in the ARTI category, is defined as a respiratory infection in which cough is the predominant symptom and there is no evidence of pneumonia. Antibiotics are often prescribed despite limited evidence that they shorten the duration of acute bronchitis. With increasing incidence of antibiotic resistance, bronchitis allows physicians to practice “prescriptive restraint” and to provide supportive therapy. Consider using the phrase “chest cold” to help patients understand the viral and benign nature of this infection. Chronic bronchitis is one of the manifestations of chronic obstructive pulmonary disease (COPD) and is defined clinically as cough and sputum production on most days for 3 months annually for 2 years. Chronic bronchitis is thought to be primarily inflammatory in origin, although infection may be associated with acute exacerbations; with increased sputum production and worsening dyspnea, antibiotics have proved effective in acute episodes. However, systemic corticosteroids are the mainstay of COPD exacerbation management. The patient with acute bronchitis presents with cough, often productive. Patients may report clear or colored mucus in association with the presumed diagnosis of acute bronchitis. Despite what many patients believe, the color of sputum, even purulent sputum, is not predictive of bacterial infection. The cough of bronchitis can last up to 4 weeks, sometimes even longer. Typically, acute bronchitis is associated with other manifestations of infection, such as malaise and fever. Respiratory viruses are thought to cause the majority of cases of acute bronchitis. Influenza A and B, parainfluenza, respiratory syncytial virus (RSV), coronavirus, adenovirus, and rhinovirus are common pathogens in the viral category. Clues to a specific virus may be found in the patient history; for example, RSV might be considered when there is household exposure to infected children. Influenza typically presents with sudden onset of symptoms, including fever, myalgias, cough, and sore throat. Neuraminidase inhibitors are modestly effective in shortening the duration of influenza in ambulatory and healthy 208

patients (by about 1 day), if initiated in the first 48 hours of illness. The resistance patterns of influenza A and B have shifted in the last several years and may vary based on yearly viral strains. Influenza B has remained, as of 2010, sensitive to zanamivir (Relenza) and oseltamivir (Tamiflu). Currently circulating strains of influenza A, both H1N1 and H3N2, and influenza B have generally remained sensitive to both oseltamivir and zanamivir (Fiore et al., 2011). Family physicians are advised to consider restraint in the prescribing of these agents, since resistance is of great concern. Yearly influenza immunization and cough etiquette and hygiene are likely the most useful techniques for influenza management. Studies have identified other pathogens, such as Mycoplasma pneumoniae and Chlamydophila pneumoniae, in a small minority of cases of clinical acute upper respiratory illness with cough as the predominant symptom. No significant benefit has been found in treating these infections with antibiotics. An exception in the treatment of acute bronchitis-like illness with antibiotics is when confirmed or probable Bordetella pertussis is present. Early treatment with a macrolide antibiotic and patient isolation will likely decrease coughing paroxysms and limit spread of disease (Braman, 2006). Although common upper respiratory bacterial pathogens, such as Moraxella (Branhamella) catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae, may be isolated from patients with acute bronchitis, their relevance is questionable because these bacteria can be present in the respiratory tract of healthy individuals. Obtaining sputum for culture when bronchitis is the diagnosis generally is not useful. Antibiotics may offer a modest benefit in the treatment of acute bronchitis, with many studies showing no statistical significance in the outcome of treated versus not-treated groups. Measures of function, such as duration of illness, loss of work, and limitation of activity, have not shown clinically significant improvement in those with acute bronchitis taking antibiotics. Coupled with cost and the potential for side effects, the use of antibiotics for acute bronchitis is not recommended. If a provider decides to use an antibiotic in a specific patient situation, narrow-spectrum respiratory agents are preferred, such as a first-generation macrolide or doxycycline. Treating the symptom of cough in acute bronchitis is an important concern for patients. In adults with acute bronchitis with signs of airway obstruction, evidenced by wheezing on examination or decreased peak expiratory flow rate, beta-2 agonists may be helpful in alleviating cough. These agents are not helpful for children with acute cough or adults with cough and no evidence of airway obstruction. Side effects of tremor and an anxious feeling must be weighed against this benefit. Patients often are primarily interested in alleviating symptoms caused by respiratory illness. Unfortunately, there is mixed evidence for the use of over-the-counter (OTC) and prescription cough medications. Dextromethorphan and codeine may be somewhat effective, although they have not been evaluated in randomized, double-blinded, placebo-controlled trials for acute bronchitis. Combination first-generation antihistamine-decongestant products may be effective for the cough associated with colds. Naproxen showed efficacy against cough in one upper respiratory model study (Sperber et al., 1992). Guaifenesin acts as an expectorant and may have some effect on cough by its mucus-thinning properties.

Infectious Diseases

Chronic Bronchitis: Acute Exacerbation Acute exacerbations of chronic bronchitis may be triggered by bacterial or viral infection or may be noninfectious. H. influenzae accounts for 50% of bacterial exacerbations with S. pneumoniae and M. catarrhalis causing an additional third (Moussaoui et al., 2008). For acute exacerbation of COPD associated with purulent sputum and increased shortness of breath, antibiotic therapy decreases mortality by 77% and treatment failure by 53% (Ram et al., 2009). This finding was true regardless of the antibiotic choice, although coverage for the organisms just noted seems rationale. Consideration of the frequency of beta-lactamase production within these organisms in a community is important. More recent meta-analysis shows that a shorter course, no longer than 5 days, is as effective as longer treatment with antibiotic (Moussaoui et al., 2008). Other features of the management of acute exacerbation of chronic bronchitis include systemic corticosteroids, inhaled beta agonists and anticholinergics (e.g., ipratropium), and support for oxygenation status and ventilation. Patients with chronic bronchitis may have multiple hospital admissions and may remain colonized with both community-acquired and hospital-acquired organisms. It is advisable to reserve the use of antibiotics, unless absolutely necessary to prevent the development of resistant organisms.

KEY TREATMENT Antibiotics for the treatment of bronchitis is not recommended because of the cost, potential for side effects, and lack of clinical benefit (Braman, 2006; Smith et al., 2009) (SOR: A). In the treatment of Bordetella pertussis, early administration of a macrolide antibiotic and patient isolation will likely decrease coughing paroxysms and limit spread of disease (Braman, 2006) (SOR: A). In adults with acute bronchitis with signs of airway obstruction, as evidenced by wheezing on examination or decreased peak expiratory flow rate, beta-2 agonists may be helpful in alleviating cough (Braman, 2006) (SOR: B). For acute exacerbation of COPD associated with purulent sputum and increased shortness of breath, treatment with antibiotics decreases mortality by 77% and treatment failure by 53% (Ram et al., 2009) (SOR: A).

PNEUMONIA

pain, and dyspnea are common symptoms of CAP. Nausea, vomiting, and diarrhea also may occur, and in elderly patients, CAP may present with mental status changes. Although its absence usually makes pneumonia less likely, fever can be absent in the elderly patient. Other physical examination findings include an elevated respiratory rate, conversational dyspnea, tachycardia, and rales. Egophony and dullness to percussion may be noted with focal consolidation. Typical laboratory findings include leukocytosis. The diagnosis of pneumonia is based on the presence of symptoms and the presence of an infiltrate on chest radiograph. If infiltrate is not present, consider obtaining a chest tomography scan (which has higher sensitivity) to rule in or rule out CAP. If negative, other diagnoses should be considered. The most common microbiologic agent of pneumonia is often not isolated (Table 16-1). Furthermore, studies have shown that bacteriologic causes of pneumonia cannot be determined by radiographic appearance (i.e., “typical” vs. “atypical”). In the proper clinical setting, certain clinical microbes should be considered because they can affect treatment considerations and epidemiologic studies. These include Legionella spp., influenza A and B, and communityacquired methicillin-resistant Staphylococcus aureus (MRSA). Certain diagnostic tests are performed based on clinical setting. Blood cultures are not routinely done in the outpatient setting but should always be done if the patient is being admitted to the hospital, ideally before antibiotics are given. The use of Gram stain and sputum culture remains controversial but can provide more evidence of a bacterial cause (e.g., many PMNs). If sputum cultures are being obtained, it is recommended that the physician have the patient expectorate directly into a specimen cup and have it sent immediately for processing. This can increase the yield of isolating Streptococcus pneumoniae among

Table 16-1 Most Common Etiologies of Community-Acquired Pneumonia

Patient Type

Etiology

Outpatient

Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory viruses*

Inpatient (non-ICU)

S. pneumoniae M. pneumoniae C. pneumoniae H. influenzae Legionella spp. Aspiration Respiratory viruses*

Inpatient (ICU)

S. pneumoniae Staphylococcus aureus Legionella spp. Gram-negative bacilli H. influenzae

Anthony Zeimet Key Points • A ssessment tools for pneumonia severity (e.g., CURB-65) can help determine the treatment approach. • The therapy of pneumonia is often empiric because the infecting organism is not readily isolated in more than 50% of cases. • Chest radiography is one of the most useful diagnostic tools in pneumonia.

Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma and, along with influenza, is the seventh leading cause of death in the United States. Fever, cough, sputum production, pleuritic chest

Modified from Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society–American Thoracic Society Consensus Guidelines on Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis 2007;44:S27-S72. ICU, Intensive care unit. *Influenza A and B, adenovirus, respiratory syncytial virus, and parainfluenza.

209

16

Infectious Diseases

other respiratory pathogens. Other tests include urine antigen tests for S. pneumoniae, Legionella pneumophila serogroup 1, and nasal swab for influenza A and B. In young children, RSV, adenovirus, and parainfluenza in addition to influenza are common causes. Nasal swab for RSV and influenza can be rapidly done, but the other causes can be determined with viral cultures, serology, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR), although results usually are received after resolution of the acute symptoms. Perhaps the most important decision for clinicians is to determine the location of treatment. The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) recommend use of the pneumonia severity index (PSI), which uses 20 variables to risk-stratify the patient into five mortality classes, or the CURB-65, which measures five clinical variables in this decision making. The CURB-65 may be the easiest and most convenient to use at the site of decision making. A score of 0 or 1 indicates treatment as an outpatient; a score of 2 requires hospital admission to the general medical ward; and a score of 3 or more indicates admission to an intensive care unit (ICU) (Box 16-1). Treatment of CAP should be targeted toward the most likely etiology (Table 16-2). Outpatient therapy for patients who have no comorbidities and have not received antibiotics within the last 3 months includes doxycycline or a macrolide antibiotic. Use of a fluoroquinolone antibiotic (levofloxacin or moxifloxacin) should be reserved for patients with more complicated pneumonia and those requiring hospitalization. Patients who have comorbid conditions or recent antibiotic exposure, or who will be hospitalized, should receive a respiratory fluoroquinolone or combination therapy with a betalactam drug plus a macrolide, for 48 to 72 hours after fever abates (usually 5-7 days’ total therapy). If an organism is isolated, therapy may be narrowed to cover the causative agent. The clinician should consider longer therapy and appropriate antibiotics to cover for infection by less common organisms such as Staphylococcus aureus or Pseudomonas aeruginosa. If the patient has no more than one abnormal value (temperature 60 on room air) and the patient is able to maintain oral intake and has a normal mental status, the clinician can safely switch to oral therapy and discharge the patient from the hospital. Unless the etiology of the pneumonia is known, the physician should switch to oral antibiotics in the same class as the intravenous antibiotics used.

Box 16-1 CURB-65 Criteria Assign a value of 1 for each variable: • Confusion: Is the patient disoriented to person, place, or time? • BUN >20 mg/dl • Respiratory rate > 30 breaths/min • Blood pressure: systolic 3: inpatient treatment in an intensive care unit BUN, Blood urea nitrogen.

210

The U.S. Preventive Services Task Force (USPSTF) along with IDSA and ATS recommend annual influenza vaccinations to those over 50 years of age, those who are (or who reside with those who are) at high risk for influenza complications, and all health care workers. Furthermore, the pneumococcal vaccine should be given to all those over age 65. Smoking cessation is also important and should be discussed at each clinic visit.

KEY TREATMENT Locally adapted guidelines should be implemented to improve the processing of care variables and relevant clinical outcomes in pneumonia (Mandell et al., 2007) (SOR: B). Objective criteria or scores should always be supplemented with physician determination of subjective factors, including the patient’s ability to take oral medication safely and reliably and the availability of outpatient support resources (Mandell et al., 2007) (SOR: B). For patients with CURB-65 score of 2 or higher, more intensive treatment (i.e., hospitalization or, where appropriate and available, intensive in-home health care services) is usually warranted (Mandell et al., 2007) (SOR: C).

INFLUENZA Anthony Zeimet Key Points • C oncerns about development of resistant seasonal and H1N1 swine-derived influenza virus should be considered in the decision to administer antiviral medications to healthy patients with these infections. • The abrupt onset of fever with chills, headache, malaise, myalgias, arthralgias, and rigors during “flu season” is sufficient to diagnose influenza. • Prevention of influenza is generally with vaccination.

Influenza deserves special mention because it is an important cause of pneumonitis and can precede a bacterial pneumonia. Influenza viruses are medium-sized enveloped ribonucleic acid (RNA) viruses that consist of a lipid bilayer with matrix proteins with spiked surface projections of glycoproteins (hemagglutinins, neuraminidase) on the outer surface (Figure 16-1). Both influenza A and influenza B have eight segmented pieces of single-stranded RNA. The only difference between influenza A and B is that B does not have an M2 ion channel. Hemagglutinins, three types of which typically infect humans (H1, H2, H3), bind to respiratory epithelial cells and allow fusion with the host cell. Neuraminidase, consisting of two types (N1, N2), allows release of virus from the infected cells. A unique aspect of influenza is that antigenic variation occurs annually. Antigenic shift is caused by a genetic reassortment between animal and human influenza strains, producing a novel virus that generally causes the worldwide pandemics. Influenza viruses circulate mostly among humans, birds, and swine. Sometimes; a human strain and an animal strain can intermingle and create a new, unique virus. This is what happened during spring 2009, heralding the most recent pandemic and creating “Novel H1N1 Influenza” (swine influenza). Genotype analysis

Infectious Diseases

Table 16-2 Guide to Empiric Choice of Antimicrobial Agent for Treating Patients with Community-Acquired Pneumonia (CAP)

Patient Characteristics

Preferred Treatment Options

Patient Characteristics

Preferred Treatment Options

Outpatient

Intensive Care Unit (ICU)

Previously Healthy

Pseudomonas infection is not an issue

A β-lactam†† plus either an advanced macrolide or a respiratory fluoroquinolone

Pseudomonas infection is not an issue but patient has a β-lactam allergy

A respiratory fluoroquinolone, with or without clindamycin

Pseudomonas infection is an issue‡‡ (cystic fibrosis, impaired host defenses)

Either (1) an antipseudomonal βlactam§§ plus ciprofloxacin, or (2) an antipseudomonal agent plus an aminoglycoside## plus a respiratory fluoroquinolone or a macrolide

Pseudomonas infection is an issue but the patient has a β-lactam allergy. Health care–associated exposure

Aztreonam plus aminoglycoside plus levofloxacin¶¶ or other respiratory quinolone Anti-Pseudomonas cephalosporin, carbapenem (not ertapenem) or β-lactam/β-lactamase inhibitor with antiPseudomonas activity plus vancomycin (for MRSA coverage) ± quinolone or aminoglycoside

No recent antibiotic therapy

Oral-based β-lactam, macrolide,* or doxycycline

Recent antibiotic therapy†

A respiratory fluoroquinolone‡ alone, an advanced macrolide* plus high-dose amoxicillin,§ or an advanced macrolide plus high-dose amoxicillin-clavulanate.¶

Comorbidities (COPD, diabetes, renal failure or congestive heart failure, or malignancy) No recent antibiotic therapy

An advanced macrolide* plus β-lactam or a respiratory fluoroquinolone

Recent antibiotic therapy

A respiratory fluoroquinolone‡ alone or an advanced macrolide plus a β-lactam**

Suspected aspiration with infection

Amoxicillin-clavulanate or clindamycin

Influenza with bacterial superinfection

Vancomycin, linezolid, or other coverage for MRSA or community-acquired MRSA

Inpatient Medical Ward No recent antibiotic therapy

A respiratory fluoroquinolone alone or an advanced macrolide plus a β-lactam††

Recent antibiotic therapy

An advanced macrolide plus a β-lactam, or a respiratory fluoroquinolone alone (regimen selected will depend on nature of recent antibiotic therapy)

Nursing Home Receiving treatment in nursing home

A respiratory fluoroquinolone alone or vancomycin (for S. aureus including MRSA) plus a β-lactam (cefepime or piperacillin/ tazobactam if Pseudomonas is suspected; ceftriaxone if Pseudomonas is not suspected)

Hospitalized

Same as for medical ward and ICU

Data from Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27-S72. COPD, Chronic obstructive pulmonary disease; MRSA, methicillin-resistant Staphylococcus aureus. *Azithromycin or clarithromycin. †That is, the patient was given a course of antibiotic(s) for treatment of any infection within the past 3 months, excluding the current episode of infection. Such treatment is a risk factor for drug-resistant Streptococcus pneumoniae and possibly for infection with gram-negative bacilli. Depending on the class of antibiotics recently given, one or another of the suggested options may be selected. Recent use of a fluoroquinolone should dictate selection of a nonfluoroquinolone regimen, and vice versa. ‡Moxifloxacin, levofloxacin, or gemifloxacin. §Dosage: 1 g orally (PO) three times daily (tid). ¶Dosage: 2 g PO twice daily (bid). **High-dose amoxicillin (1 g tid), high-dose amoxicillin-clavulanate (2 g bid), cefpodoxime, cefprozil, or cefuroxime. ††Cefotaxime, ceftriaxone, ampicillin-sulbactam, or ertapenem. ‡‡The antipseudomonal agents chosen reflect this concern. Risk factors for Pseudomonas infection include severe structural lung disease (e.g., bronchiectasis) and recent antibiotic therapy, health care–associated exposures or stay in hospital (especially in the ICU). For patients with CAP in the ICU, coverage for S. pneumoniae and Legionella species must always be considered. Piperacillin-tazobactam, imipenem, meropenem, and cefepime are excellent β-lactams and are adequate for most S. pneumoniae and H. influenzae infections. They may be preferred when there is concern for relatively unusual CAP pathogens, such as P. aeruginosa, Klebsiella spp., and other gram-negative bacteria. §§Piperacillin, piperacillin-tazobactam, imipenem, meropenem, or cefepime. ##Data suggest that older adults receiving aminoglycosides have worse outcomes. ¶¶Dosage for hospitalized patients, 750 mg/day.

of this strain determined that components came from an influenza virus circulating among swine herds in North America that combined with a virus circulating among ill swine in Eurasia, creating a new influenza strain capable of causing disease in humans. Because this virus had not previously infected humans, it had the potential to cause

widespread morbidity and mortality worldwide. During pandemics, the U.S. Centers for Disease Control and Prevention (CDC) estimates an additional 10,000 to 40,000 deaths caused by influenza. Although higher than in nonpandemic years, mortality was significantly less than initially predicted in 2009. 211

16

Infectious Diseases

Neuraminidase

Viral envelope

Hemagglutinin

Gene segment -RNA -Nucleoprotein -Polymerase proteins M1 protein

M2 Protein

Figure 16-1 Schematic model of influenza A virus. (From Treanor JJ: Influenza viruses, including avian influenza and swine influenza. In Mandell GL, Bennett JE, Dolin RD (eds). Mandell, Douglas, and Bennett’s Principles and Practices of Infectious Diseases, 7th ed. Philadelphia, Churchill Livingstone, 2010, p 2266.)

The abrupt onset of fever, along with chills, headache, malaise, myalgias, arthralgias, and rigors during “flu season,” is sufficient to diagnose influenza. As the fever resolves, a dry cough and nasal discharge predominate. A rapid nasal swab or viral cultures can be used to confirm the diagnosis of influenza but is rarely needed. In fact, the sensitivity of these rapid tests can range from 50% to 70%, so a negative test does not rule out influenza. The primary care physician needs to determine if the patient has influenza or the common cold, because symptoms of both illnesses generally overlap (Table 16-3). Treatment of influenza is generally not necessary because it is usually a self-limiting condition. Treatment should be reserved for those with comorbidities who present within 48 hours of symptom onset. Neuraminidase inhibitors (zanamivir and oseltamivir) prevent the release of virus from the respiratory epithelium and are approved for both influenza A and influenza B. The M2 inhibitors (amantadine and rimantadine) are approved by the U.S. Food and Drug Administration (FDA) for the treatment of influenza A because these drugs block the M2 ion protein channel, preventing fusion of the virus to host cell membrane (influenza B has no M2 ion channel). The use of M2 inhibitors is limited because of increasing resistance among influenza A viruses, as well as causing central nervous system (CNS) problems that are usually exacerbated in elderly persons, who are more likely to seek treatment for influenza (Table 16-4). The major complication of influenza is a secondary bacterial pneumonia or exacerbation of underlying COPD. Initial improvement in clinical symptoms followed by deterioration usually suggests a secondary bacterial pneumonia, which can usually be confirmed with a chest radiograph showing an infiltrate. Other, less common complications of influenza 212

Table 16-3 Common Cold versus Influenza Symptoms

Symptom

Common Cold

Influenza

Fever

Rare

Abrupt onset

Cough

Frequent, usually hacking

Frequent, usually severe

Sore throat

Frequent

Rare

Nasal congestion

Frequent

Rare

Sneezing

Frequent

Rare

Myalgia

Rare

Frequent

Headache

Rare

Frequent

Fatigue

Mild

Severe

include myositis, myocarditis, pericarditis, transverse myelitis, encephalitis, and Guillain-Barré syndrome. Prevention of influenza is generally with vaccination. Box 16-2 outlines patients at risk for influenza complications who should be vaccinated yearly. Although anyone wanting an influenza vaccine should be vaccinated, during periods of vaccine shortage, high-risk groups have priority. A well-matched vaccine can prevent influenza among 70% to 90% of adults and decrease work absenteeism. Conversely, a poorly matched vaccine only prevents influenza in 50% of healthy adults. Proper hand hygiene and covering one’s cough are two additional important components in preventing the spread of influenza virus.

KEY TREATMENT Early treatment (within 48 hours of onset of symptoms) with oseltamivir or zanamivir is recommended for influenza A (Jefferson et al., 2006) (SOR: A). Use of oseltamivir and zanamivir is not recommended for patients with uncomplicated influenza with symptoms for more than 48 hours (Kaiser and Hayden, 1999) (SOR: A). Oseltamivir and zanamivir may be used to reduce viral shedding in hospitalized patients or to treat influenza pneumonia (Mandell et al., 2007) (SOR: C).

SYSTEMIC VIRAL INFECTIONS Anthony Zeimet Key Points • P opulation-based vaccination programs have been highly effective in decreasing the incidence of many viral infections. • Acyclovir can be used in adults and children with varicella to decrease symptoms if given in the first 48 hours after rash onset, but its benefit must be weighed against its cost and the possibility of development of viral resistance. • Antiviral medications should be considered to decrease the incidence of postherpetic neuralgia, particularly in older patients.

Infectious Diseases

Table 16-4 Treatment and Chemoprophylaxis Recommendations for Influenza

Agent/ Group

Treatment

Chemoprophylaxis

Neuraminidase Inhibitors Oseltamivir Adults

75-mg capsule twice daily (bid) for 5 days

75-mg capsule once daily (qd)

Children (age >12 mo) 40 kg

160 mg/day in 2 doses

75 mg qd

Two 5-mg inhalations (10 mg bid)

Two 5-mg inhalations (10 mg qd)

Two 5-mg inhalations (10 mg bid)(age >7 yr)

Twp 5-mg inhalations (10 mg qd)(age >5 yr)

Zanamivir Adults Children

M2 Inhibitors (Adamantadines)* Rimantadine† Adults

200 mg/day as either a single daily dose or divided into 2 doses


1-9 yr

6.6 mg/kg/day (max, 150 mg/day) divided in 2 doses

5 mg/kg qd, not to exceed 150 mg

>10 yr





1-9 yr

5-8 mg/kg/day divided into 2 doses or as a single daily dose (max, 150 mg/day)

5-8 mg/kg/day divided into 2 doses or as a single daily dose (max, 150 mg/day)

9-12 yr

200 mg/day divided into 2 doses

200 mg/day divided into 2 doses

Children

Amantadine Adults

Children

Modified from Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis, and institutional outbreak management. Clinical Practice Guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003-1032. *The amantadines should be used only when influenza A (H1N1) infection or exposure is suspected. The amantadines should not be used for infection or exposure to influenza A (H2N3) or influenza B. †Rimantadine has not been approved by the U.S. Food and Drug Administration for treatment of children, although published data exist on safety and efficacy in the pediatric population.

Box 16-2 Groups at risk for Influenza Complications* Unvaccinated infants age 12 to 24 months Persons with asthma or other chronic pulmonary disease, such as cystic fibrosis in children or chronic obstructive pulmonary disease in adults Patients with hemodynamically significant cardiac disease Patients with immunosuppressive disorders or receiving immunosuppressive therapy Patient with human immunodeficiency virus (HIV) infection Patients with sickle cell anemia and other hemoglobinopathies Patients with disease requiring long-term aspirin therapy (e.g., rheumatoid arthritis, Kawasaki disease) Patients with chronic renal obstruction Patients with cancer Patients with chronic metabolic disease, such as diabetes mellitus Patient with neuromuscular disorders, seizure disorders, or cognitive dysfunction that may compromise the handling of respiratory secretions Adults older than 66 years Residents of any age of nursing homes or other long-term care facilities Modified from Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis, and institutional outbreak management. Clinical Practice Guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003-1032. *Data suggest that the highest risk of both mortality and serious morbidity (e.g., hospitalization) occurs in severely immunocompromised patients (e.g., hematopoietic stem cell transplant patients) and very elderly (>85 years) residents of nursing homes; infants under age 24 months also have high hospitalization rates but lower case-fatality rates than the other two groups.

• M easles has had a resurgence in recent years and should be suspected when a patient presents with cough, coryza, conjunctivitis, and head-to-toe rash. • Epstein-Barr virus and cytomegalovirus infections are generally not clinically distinguishable, and their treatment is primarily supportive.

Vaccinations have dramatically decreased the incidence of a number of historically common viral infections; smallpox has been eradicated through widespread vaccination. However, recent outbreaks of measles and mumps on college campuses underscore the need to remain vigilant in administering vaccines at the population level, even though no vaccine is available for many common viruses.

Varicella and Herpes Zoster Varicella is one of the classic viral exanthems of childhood. Before routine vaccination, having chickenpox was one of childhood’s “rites of passage.” The virus, a herpesvirus (human herpesvirus 3), is effectively transmitted, causing outbreaks in schools and households. Patients with primary varicella present with fever, headache, and sore throat. Generally within 1 to 2 days of onset of symptoms, a papulovesicular rash erupts diffusely. The classic description of the chickenpox lesion is “a dewdrop on a rose petal,” suggesting a central vesicle on an erythematous base. Lesions continue to appear for 5 to 7 days. All lesions going from papule to vesicle to crusted lesion takes about 213

16

Infectious Diseases

2 weeks. Patients are considered to be infectious, primarily through respiratory secretions, during the 2 days before symptoms appear and until all lesions are crusted. Treatment of varicella is generally supportive. Control of spread may be a concern in group-living environments such as schools or residence halls. Isolation of the infected patient away from those susceptible to varicella infection is standard practice. Acyclovir can be started within the first 24 hours after rash eruption to achieve an attenuation of the infectious course. In children, this means a decrease in the duration of fever by about 1 day and a decrease in the number of lesions (Swingler, 2010). In adults, acyclovir decreases rash duration and the number of lesions, although the results are less significant than for children. Adult dosing of acyclovir for varicella is 800 mg five times daily. The marginal benefit must be weighed against the possible development of resistance at a population level and the cost of the medication. Complications of varicella can include secondary infection of skin lesions, pneumonitis, encephalitis, and dehydration from vomiting and diarrhea. Varicella is prevented primarily through administration of vaccine. The vaccine is highly effective in children, with recommended dosing at 12 to 15 months with a second dose at 4 to 6 years. Varicella is now included in a measles-mumpsrubella (MMR) vaccine, which can be given between 12 months and 12 years of age. The varicella vaccine is a live, attenuated virus and should not be given to certain immunocompromised patients. The vaccine can also be administered to exposed immunocompetent contacts, although the benefit is clearer for children than adults. Severely immunocompromised patients exposed to varicella (particularly those with advanced HIV disease) may be given high-dose acyclovir to prevent development of disease. Herpes zoster is a reactivation of the neurotropic varicella virus, typically in a dermatomal distribution. This is more common in elderly or immunocompromised patients but can occur in healthy people as well. Patients with zoster may note generalized malaise, hyperesthesia, numbness, tingling, and pain in the skin before development of a rash. The appearance of the rash is the same as for chickenpox, although most often isolated to a unilateral dermatome. The diagnosis of herpes zoster is clinical based on the history and the classic appearance of the rash. In immunocompromised patients, however, the rash may not be dermatomally isolated. When the diagnosis is unclear, viral culture can be obtained from the base of a lesion. Antiviral medications are likely to decrease the incidence of postherpetic neuralgia and are recommended, particularly in elderly patients (Wareham, 2010). Valacyclovir (1 g three times daily) or famciclovir (500 mg every 8 hours) for 7 days is likely more effective than acyclovir in achieving this result. Either drug should be started as soon after the diagnosis as possible, preferably within 48 to 72 hours of rash onset. When patients have established postherpetic neuralgia, gabapentin and tricyclic antidepressants are helpful in alleviating the pain. The rash of zoster is infectious to the touch. Patients should be advised to keep the rash covered until all the lesions have crusted. Zoster of the trigeminal nerve can extend to the eye and warrants immediate ophthalmologic intervention. A vaccine to prevent herpes zoster in adults was released in 2006. The zoster vaccine differs from the varicella vaccine in 214

that the amount of attenuated virus is 14 times higher in the zoster vaccine. The vaccine decreases the incidence of zoster by 50%. It is recommended for administration by the American Academy of Family Physicians (AAFP) to adults over age 60, regardless of prior varicella or zoster history. Although generally well tolerated, the vaccine is somewhat costly.

Measles In 2008, more measles cases were reported than in any other year since 1997 (CDC, 2010). Measles is the “first disease” of childhood from the history of medicine. In adults, measles infection may be acquired in the face of waning immunity from remote immunization. A booster dose of MMR vaccine is recommended before college entry. Clinically, measles presents with cough, coryza (nasal irritation and congestion), and conjunctivitis. Fever is common several days before the onset of the rash. The rash of measles typically spreads from head to toe and has an erythematous, papular appearance with a “sandpaper” feeling. Koplik’s spots are erythematous papules with a bluish center on the oral mucosa and appear early in measles. Measles is highly contagious through droplets. Lymphopenia and neutropenia are common laboratory findings with measles infection. Complications of measles include primary infections such as pneumonia, gastroenteritis, encephalitis, and the rare subacute sclerosing panencephalitis. Secondary infections such as otitis media, pneumonia, and adenitis may also occur. Treatment is supportive, and the implications of measles infection are primarily in the public health realm. Patients with measles should be isolated for at least 4 days after the appearance of the rash. It is important to recognize that patients are contagious for 2 days before the development of symptoms. Careful verification of immunization status for close contacts is essential.

Epstein-Barr Virus and Cytomegalovirus Clinical infectious mononucleosis is a common infection in adolescents and early adults. The clinical syndrome is most often caused by Epstein-Barr virus (EBV), although cytomegalovirus (CMV) may also be the source in this clinical syndrome, which includes fever, exudative tonsillitis, adenopathy (often including posterior cervical or occipital nodes), and fatigue. EBV is transmitted in oral secretions and may be transmitted sexually as well. B cells are infected with EBV either directly or after contact with epithelial cells, resulting in diffuse lymphoid enlargement. The diagnosis of infectious mononucleosis is made by recognizing the clinical symptoms of fever, pharyngitis, and adenopathy along with the laboratory findings of greater than 50% lymphocytes with 10% or more atypical lymphocytes (Hoagland, 1952). Also, a positive serologic test for heterophile antibody assists the family physician in the diagnosis. To differentiate EBV from CMV mononucleosis, serology (IgG and IgM) may be obtained. Results of these tests are generally not available in time to have a significant benefit clinically. Splenic enlargement as part of this lymphoid hypertrophy can lead to splenic rupture (0.1% risk) (Dommerby

Infectious Diseases

et al., 1986). Athletes with infectious mononucleosis must be managed carefully to avoid their participation in sports that could result in abdominal trauma. Other risks associated with infectious mononucleosis include upper airway obstruction, asymptomatic transaminase elevation, thrombocytopenia, and rash after the administration of ampicillin or amoxicillin. Routinely obtaining transaminase levels in patients without clinical hepatitis is of little value and can increase the overall cost of management. Treatment of infectious mononucleosis is largely supportive. Patients should be instructed to treat fever with antipyretics, rest, and expect symptom duration of 2 to 4 weeks, although symptoms can last for several months. The use of steroids, such as prednisone, has shown limited benefit. Data suggest an initial benefit 12 hours after steroid administration, although this is lost within several days (Candy and Hotopf, 2006). Combination of steroid and an antiviral (valacyclovir) may have some positive effect on fatigue.

KEY TREATMENT Acyclovir started within the first 24 hours after varicella rash eruption can attenuate the infectious course, decreasing duration of fever by 1 day and reducing the number of lesions (SOR: A). Administration of varicella vaccine to a susceptible child within 3 days of exposure will likely modify or prevent disease (Macartney and McIntyre, 2008) (SOR: A). Antiviral medications decrease the incidence of postherpetic neuralgia (Wareham, 2010) (SOR: B).

TUBERCULOSIS David McCrary

roplets are spread by coughing. Brief contact carries little d risk for acquiring TB, and infection generally does not occur in open air; open-air sanatoriums were the cornerstone of TB treatment before antimicrobial therapy.

Epidemiology In the United States, TB incidence rates have been on the decline since 1992, coinciding with the control of HIVinduced AIDS by antiretroviral therapy. However, TB remains prevalent in certain high-risk groups (i.e. immigrants, IV drug use, homeless persons). Most cases of TB are in people age 15 to 49 years. TB in elderly persons is generally caused by a reactivation of latent infection acquired in the remote past, whereas TB in young children indicates ongoing active transmission in the community. Infection in children is more likely to progress to active TB and disseminated disease. Persons with HIV infection have a disproportionately higher risk for acquiring TB than the general population.

Presentation Tuberculosis is most frequently manifested clinically as pulmonary disease, but it can involve any organ. Extrapulmonary TB accounts for about 20% of disease in HIV-seronegative persons but is more common in HIV-seropositive persons. Pulmonary TB typically manifest with fever, night sweats, chronic cough, sputum production, hemoptysis, anorexia, and weight loss. Chest radiographs in patients with pulmonary TB typically reveal upper-lobe cavitary lesions and can reveal infiltrates or nodular lesions, as well as lymphadenopathy (Figure 16-2). TB in the setting of advanced HIV co-infection does not generally manifest in the typical manner (Table 16-5).

Key Points • T he most common presentation of tuberculosis is pulmonary disease. • Tuberculosis is diagnosed by acid-fast bacilli smears and cultures. • Standard first-line agents to treat TB are isoniazid, rifampin, pyrazinamide, and ethambutol. • High-risk patients with a positive purified protein derivative skin test or Quantiferon-TB Gold test should be treated for latent TB infection. • The current recommendation for first-line treatment for latent TB is 9 months of oral isoniazid. Tuberculosis skin testing should be interpreted without regard to bacille Calmette-Guérin (BCG) history, because BCG is administered in areas where TB is endemic and BCG does not provide complete protection from TB infection.

Tuberculosis (TB) is a disease that has plagued humans since antiquity, with evidence of spinal TB in neolithic and early Egyptian remains. At present, TB affects approximately one third of the world’s population. TB is the world’s second most common cause of death from infectious disease after human immunodeficiency virus or acquired immunodeficiency syndrome (HIV/AIDS). Tuberculosis is caused by Mycobacterium tuberculosis, an acid-fast bacillus. TB is acquired by inhalation of respiratory droplets. These respiratory

Figure 16-2 Chest radiograph showing right apical infiltrate typical of a patient with primary tuberculosis. (From Fitzgerald D, Sterling T, Haas D. Mycobacterium tuberculosis. In Mandell GL, Bennett JE, Dolin R (eds). Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th ed. Philadelphia, Churchill Livingstone, 2010, p 3141.)

215

16

Infectious Diseases

Diagnosis

Treatment

The diagnosis of pulmonary TB is made by the demonstration of acid-fast bacilli (AFB) in sputum and the growth of M. tuberculosis in culture. These patients typically have an abnormal chest radiograph, as previously described. M. tuberculosis is a slow-growing bacterium, and cultures can take up to 6 weeks to grow. A PCR assay developed for M. tuberculosis can be run on AFB smear–positive sputum to hasten the diagnosis of pulmonary TB. A positive PCR on AFB-positive sputum is diagnostic of pulmonary TB, but a negative test does not rule out the diagnosis.

Patients with AFB positive smears from sputum samples should be started on anti-TB therapy while awaiting results of PCR and cultures. The treatment of TB always uses multiple agents with anti-TB activity. Single agents should never be used. The standard first-line agents are isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) (Figure 16-3 and Table 16-6). If administered, INH should be given with pyridoxine (vitamin B6; 25-50 mg orally daily) to prevent neuropathy. Treatment of active pulmonary TB is generally for 6 months regardless of HIV status, but treatment may need to be extended in certain situations. Directly observed therapy (DOT) is the preferred mechanism of administration to ensure compliance. Many local county and state health departments have systems for DOT. Treatment of HIV-seropositive patients with TB who are receiving an antiretroviral (ARV) regimen that contains a protease inhibitor is complicated by the latter’s interaction with rifamycins (particularly rifampin). Management of such patients should be coordinated with an infectious diseases specialist, who also should manage drug-resistant TB treatment.

Table 16-5 Clinical Manifestations of Active Tuberculosis in Early verus Late* Human Immunodeficiency Virus Infection

Sign

Early

Late

Tuberculin test

Usually positive

Usually negative

Adenopathy

Unusual

Common

Pulmonary distribution

Upper lobe

Lower and middle lobes

Cavitation

Often present

Typically absent

Extrapulmonary disease

10%-15% of cases

50% of cases

Latent Tuberculosis Infection and Purified Protein Derivative In the United States, latent tuberculosis infection (LTBI) is the most prevalent form of tuberculosis. LTBI is the term given to patients with a positive purified protein derivative (PPD) skin test without evidence of active TB. PPD has been used for more than 100 years and relies on delayed-type hypersensitivity (DTH) to M. tuberculosis cellular proteins.

Modified from Murray JF. Cursed duet: HIV infection and tuberculosis. Respiration 1990;57:210-220. *For practical purposes, “early” and “late” may be defined as CD4+ cell counts >300 cells/mm3 and 1 month, bronchitis, pneumonitis, esophagitis) Progressive multifocal leukoencephalopathy

Fungal

• • • •

andidiasis of the esophagus, bronchi, trachea, or C lungs Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Histoplasmosis, disseminated or extrapulmonary 251

17

Care of the Adult HIV-Infected Patient

Table 17-1 CDC Classification System of HIV/AIDS

Clinical Categories CD4 Cell Count

A Asymptomatic Acute HIV or PGL

B Symptomatic state Neither A nor C

C AIDS Indicator Conditions

≥500 cells/mm3

A1

B1

C1

200-499 cells/mm3

A2

B2

C2

A3

B3

C3

1 month) Pneumonia, recurrent (Pneumocystis jiroveci)

Parasitic

• • •

ryptosporidiosis, chronic intestinal (persisting for >1 C month) Toxoplasmosis of brain Isosporiasis, chronic intestinal (persisting for >1 month)

Box 17-2 WHO Clinical Staging of HIV/AIDS

Primary HIV infection Asymptomatic Acute retroviral syndrome

Clinical Stage 1 Asymptomatic Persistent generalized lymphadenopathy

HIV-Related Conditions

Clinical Stage 3

• •

Moderate unexplained weight loss (10% body weight with either chronic diarrhea of >2 stools/day × 1 month or chronic weakness and documented fever >1 month)

Cancers

• • •

ervical cancer, invasive C Kaposi’s sarcoma Lymphoma (Burkitt’s, immunoblastic, or primary lymphoma of brain) Cancers and chronic renal failure associated with AIDS and lipodystrophy, insulin resistance, osteoporosis, and cardiovascular complications of HAART are being increasingly recognized and addressed.

Natural History and Clinical Course Key Points • A bout 20% of HIV-infected persons are unaware of their status because they look and feel healthy. • Primary HIV infection manifests as a flulike syndrome 1 to 6 weeks after exposure. • Symptoms include fever, pharyngitis, rash, myalgias, and meningismus; viral load is very high. • The asymptomatic phase (8-12 weeks later) can persist for many years. • The lower the viral set point, the better is the long-term prognosis.

More than one fifth of people infected with HIV are unaware of the infection because they look and feel healthy. Family physicians are likely to be the first health 252

Clinical Stage 3 Severe, unexplained weight loss (>10% body weight) Unexplained diarrhea longer than 1 month Unexplained, persistent, constant or intermittent fever longer than 1 month (>37.6° C) Persistent oral candidiasis Oral hairy leukoplakia Pulmonary tuberculosis Severe presumed bacterial infections (pneumonia, empyema, pyomyositis, bone and joint infections, meningitis, bacteremia) Acute necrotizing gingivitis, stomatitis, periodontitis Unexplained anemia (hemoglobin 480

Budesonide DPI

90, 80, or 200 μg/inhalation

180-600

>600-1200

>1200

Flunisolide

250 μg/puff

500-1000

>1000-2000

>2000

Flunisolide HFA

80 μg/puff

320

>320-640

>640

HFA/MDI

44, 110, or 220 μg/puff

88-264

>264-440

>440

DPI

50, 100, or 250 μg/inhalation

100-300

>300-500

>500

Mometasone DPI

200 μg/inhalation

200

400

>400

Triamcinolone acetonide

75 μg/puff

300-750

>750-1500

>1500

Fluticasone

From National Heart, Lung and Blood Institute, NHI, Expert Panel 3 (EPR3). Guidelines for the Diagnosis and Management of Asthma. National Asthma Education and Prevention Program (NAEPP) Coordinating Committee, 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. HFA, Hydrofluoroalkane; DPI, dry powder inhaler; MDI; metered-dose inhaler.

Prevention Even though dust mites are usually mentioned as a controllable environmental trigger, a Cochrane review of 49 controlled trials found no evidence that either physical or chemical methods aimed at reducing exposure to house dust mite allergens had any benefit (Gotzsche et al., 2004). On the other hand, a controlled trial of an intervention to reduce cockroach and dust mite allergens and passive exposure to tobacco smoke among urban children with atopic asthma was effective in reducing both allergens in the home and asthma symptom-days (Morgan et al., 2004). Teaching patients to self-monitor and self-manage their asthma using an action plan and ongoing review with their physician is effective in reducing exacerbations and symptoms (Gibson et al., 2002). As with most pulmonary diseases, the most effective preventive strategy is to eliminate smoking as a risk factor from the patient, the household, and the workplace.

Chronic Obstructive Pulmonary Disease and Chronic Bronchitis Key Points • Because of the global spread of tobacco addiction, chronic obstructive pulmonary disease (COPD) will become the world’s third leading cause of death by 2020. • Quitting smoking reduces progressive loss of pulmonary function in patients with COPD, even in long-time smokers. • The 6-minute walk test correlates strongly with quality of life and functional limitations in patients with COPD and other chronic lung diseases. • Nocturnal home oxygen therapy improves symptoms and survival in patients with hypoxia at rest. Pulmonary rehabilitation improves symptoms but not survival.

• Inhaled corticosteroids, long-acting β2-agonists, and long-acting anticholinergics (tiotropium) each decrease exacerbation rates by 20% to 25% in patients with moderate to severe COPD, although patients may differ in their response to each therapy.

Consensus statements from the Global Initiative for Chronic Obstructive Lung Disease (GOLD standards, 2005) define chronic obstructive pulmonary disease as a postbronchodilator FVC of less than 80% of predicted in a patient with evidence of airway obstruction (FEV1/FVC ratio 20% on wet-mount (74% sens, 86% spec) 3. Homogeneous discharge, gray, adherent, but wipes off easily (79% sens, 54% spec) 4. Whiff test (amine odor when KOH added; 67% sens, 93% spec)

IUC, Intrauterine contraceptive.

Figure 25-1 Bacterial vaginosis. Typical clue cells of vaginal epithelium are heavily covered by coccobacilli, with loss of distinct cell margins. (Magnification ×400.) (From Holmes KK. Lower genital tract infections in women: cystitis/urethritis, vulvovaginitis, and cervicitis. In Holmes KK, Mårdh PA, Sparling PF, et al [eds]. Sexually Transmitted Diseases. New York, McGraw-Hill, 1984.

There are many effective options for the treatment of BV. A 2009 Cochrane review states that clindamycin and metronidazole have equivalent efficacy, regardless of regimen. The standard oral dose of metronidazole for BV is 500 mg

Modified from Gutman RE et al. Evaluation of clinical methods for diagnosing bacterial vaginosis. Obstet Gynecol 2005;105:551-556. *A score of 3 of 4 is diagnostic.

sens, Sensitivity; spec, specificity; KOH, potassium hydroxide.

twice daily for 7 days. Both metronidazole and clindamycin vaginal cream are dosed daily. Clindamycin has lower adverse event rates. Intravaginal lactobacilli gelatin tablets are also effective (Oduyebo et al., 2009). The 2006 CDC guidelines do not recommend treatment with single-dose metronidazole. Tinidazole is effective with no serious side effects but is more expensive (Livengood et al., 2007). The FDA has recently approved metronidazole, 750 mg daily for 7 days, and a single dose of intravaginal clindamycin for treatment of BV, but only limited data are available on efficacy (CDC, 2006). Hydrogen peroxide douching and triple-sulfonamide cream are considered ineffective (Oduyebo et al., 2009). Recurrent BV can present a treatment challenge. If recurrence is suspected, the diagnosis should be confirmed, risk factors identified and controlled, and other causes considered while retreating BV (Alfonsi et al., 2004). Metronidazole gel used twice weekly reduces recurrence of BV but is offset by increased vaginal candidiasis and pain complaints. (Sobel et al., 2006). If retreatment fails, suppressive therapy with metronidazole 0.75% gel for 10 days, then twice weekly for 4 to 6 months, should be tried. There is no evidence that treatment of sexual partners (BASHH, 2006) or using oral or vaginal Lactobacillus acidophilus is effective to prevent recurrence (Alfonsi et al., 2004).

Candidal Vaginitis Vulvovaginal candidiasis (VVC) is the second most common cause of vaginitis after BV, with a lifetime prevalence in women of 70% to 75% (Spence, 2007). Candida albicans is the most common etiology (80%-90%). Type 1 diabetes 461

25

Gynecology

KEY TREATMENT All symptomatic women with BV should be treated (BAASH, 2006). Asymptomatic women undergoing abortion or hysterectomy should be treated to decrease the risk for infectious complications (BAASH, 2006). Oral or vaginal metronidazole (BAASH, 2006) and vaginal clindamycin are effective and equivalent in nonpregnant women (Kane, 2001). Treatment of male partners does not decrease relapse rates (BASHH, 2006). Tinidazole is effective with no serious side effects but is more expensive than metronidazole (Livengood et al., 2007) (SOR: A). In recurrent BV, suppressive therapy with metronidazole 0.75% gel for 10 days then twice weekly for 4 to 6 months may be successful (Alfonsi et al., 2004) (SOR: C).

is the strongest risk factor for VVC; other risk factors include recent antibiotic use, condom and diaphragm use, spermicide use, receptive oral sex, OC use, pregnancy, and immunosuppression. Patient self-diagnosis of VVC is incorrect 50% of the time and is therefore unreliable. Asymptomatic treatment of VVC is not recommended, even in women who have a positive swab for Candida (Spence, 2007). Because VVC is not sexually transmitted, routine partner treatment is also not recommended. Recurrent VVC is defined as four or more symptomatic episodes in a year. Rare complications of VVC include vulvar vestibulitis and chorioamnionitis (French et al., 2004). The most common complaint associated with culture confirmed VVC is burning or pruritus. A thick, curdled-appearing discharge, signs of inflammation, and lack of odor all have high positive predictive value for diagnosing VVC (Anderson et al., 2004). In one study, however, a thin discharge was present in about half of women, later found to have VVC (French et al., 2004). Although office microscopy is the first line for diagnosis of VVC, culture is the “gold standard” (Fig. 25-2) (ACOG, 2006). With Candida albicans, the vaginal pH is usually 5.0 or less but may be higher with non-albicans species. A wet mount should be performed to exclude trichomoniasis or BV. Potassium hydroxide (KOH) examination should also be performed, but it has a wide range of sensitivity. Thus, if candidiasis is suspected in a patient with persistent or recurrent symptoms and a wet mount and KOH are negative, a culture should be performed (French et al., 2004). The use of rapid antigen testing to detect vaginal yeast is more sensitive than a wet mount and is feasible for office practice. However, a negative result lacks sensitivity to rule out yeast, and a culture needs to be sent (Chatwani et al., 2007). The imidazoles are the cornerstone of VVC treatment. Intravaginal OTC imidazoles (e.g., clotrimazole, miconazole, tioconazole) come in 1-, 3-, and 7-day therapy regimens and are equivalent to oral therapies for treatment, and singledose therapy seems as efficacious as multidose therapy over days. The comparative efficacy of different azoles and of different durations of multidose regimens is unclear (Spence, 2007). Lactobacillus, administered vaginally, orally, or both, does not prevent postantibiotic-associated vaginal candidiasis (Priotta et al., 2004). Recurrent VVC occurs in 5% to 8% of women. The Infectious Diseases Society of America recommends treating recurrent VVC for 10 to 14 days, followed by suppressive therapy using fluconazole, a single 150-mg dose weekly for 462

Figure 25-2 Candidal vaginitis (vulvovaginal candidiasis). Candidal organisms in a saline wet-mount preparation clearly demonstrate hyphae and conidia under high-power magnification. (From Kaufman RH, Faro S: Benign Disease of the Vulva and Vagina, ed 4. St. Louis, Mosby, 1994.)

6 months (Pappas et al., 2009). It is unclear if oral regimens are better than intravaginal administration. In preventing recurrence, there is no evidence of benefit with intravaginal boric acid, tea tree oil, garlic, oral yogurt, douching, or treating a woman’s male sexual partner. Douching is associated with increased pelvic infections (Spence, 2007). For specific treatment regimens: see http://www.cdc.gov/std/treatment/.

KEY TREATMENT Oral fluconazole and itraconazole are both effective for vulvovaginal candidiasis (Spence, 2007) (SOR: A). Oral and intravaginal regimens are equivalent, so cost and patient preference should guide choice (Nurbhai et al., 2009) (SOR: B). Intravaginal imidazoles are equivalent to oral therapies for VVC treatment, and single-dose seems as efficacious as multidose therapy (Spence, 2007) (SOR: B). Treat recurrent VVC for 10 to 14 days, followed by suppressive therapy using fluconazole, single 150-mg dose weekly for 6 months (Pappas et al., 2009) (SOR: A)

Trichomoniasis Trichomoniasis is caused by a motile protozoan and affects 120 million women worldwide every year. It is usually sexually transmitted and is associated with transmission of other

Gynecology

STIs (Forna, 2009). Risk factors for acquisition include multiple sexual partners and possibly a decrease in the normal vaginal acidity. Men are usually asymptomatic carriers, but 10% of nongonococcal urethritis in men is caused by Trichomonas (French et al., 2004). Up to 50% of women with trichomoniasis are asymptomatic. Symptomatic women may complain of a yellow-green, malodorous discharge, vaginal burning, and dysuria. On physical examination, hemorrhagic, punctate cervical lesions are pathognomonic but are only present in 2% of cases (French et al., 2004). More common signs are foul-smelling purulent discharge, vaginal tenderness, vulvar erythema and edema. The vaginal pH is usually basic. Office microscopy is first line for diagnosis of trichomoniasis (ACOG, 2006). The sample should be taken from the posterior vault, diluted in 2 drops of saline, and assessed quickly because motility of the protozoa diminishes rapidly (Fig. 25-3). Although microscopy has good specificity (99%), motile trichomonads are seen in only 50% to 80% of culture-proven cases. Thus, culture is the gold standard. Trichomonads can be reported on a Pap smear, but it is not recommended as a diagnostic test because of the low sensitivity (58%) (French et al., 2004). In men the wet prep has poor sensitivity, so culture of both a urethral sample and a firstvoided urine sample is necessary to increase the diagnostic rate. Metronidazole or tinidazole single-dose therapy is effective for treatment of trichomoniasis. An alternative effective regimen is metronidazole, 500 mg orally twice daily for 7 days. Metronidazole gel is less effective (16,000 participants) population-based study of women between 50 and 79 years studying the effectiveness of estrogen plus progestin on congestive heart disease (CHD) prevention. The trial was stopped early because of excess cardiovascular and breast cancer events. There was an excess of 7 CHD events, 8 strokes, 8 breast cancers, and 14 venous thromboembolic events per 10,000 women. The estrogen-only arm of the study was stopped 2 years later due to excess strokes (12 per 10,000 women). There was no statistically significant increase in breast cancer incidence in the estrogen-only group (Anderson et al., 2004). The HT group in both arms of the study had fewer hip fractures. The estrogenplus-progestin group also had fewer cases of colon cancer (Roussouw et al., 2002).

Gynecology

KEY TREATMENT Hormone therapy can be used for treatment of menopausal symptoms but should be used at the lowest possible dose for the shortest time possible (NAMS, 2004) (SOR: C). Atrophic vaginitis is treated most effectively by vaginal estrogen cream or tablets, usually three times a week initially and titrated down based on symptoms (Castelo-Branco et al., 2005) (SOR: A). Antidepressant medications (fluoxetine, paroxetine, venlafaxine) are better than placebo in treating hot flashes (Grady, 2006) (SOR: A). Gabapentin (900 mg daily) is also better than placebo in treating hot flashes (Grady, 2006) (SOR: A). Stress management and meditation show promise in controlling troublesome menopausal symptoms (Tremblay et al., 2008) (SOR: B).


Web Resources www.ahrq.gov/CLINIC/uspstfix.htm U.S. Preventive Services Task Force screening recommendations, includes the Electronic Preventive Services Selector (enter a patient’s age and gender and receive a list of evidence-based recommendations) and the option to sign up for e-mail updates on preventive services. www.cdc.gov/vaccines/recs/ACIP/default.htm Centers for Disease Control and Prevention and Advisory Committee on Immunization Practices immunization guidelines, including tables for adults, adolescents, and pregnant women; e-mail updates also available.

www.asccp.org/consensus/cytological.shtml www.asccp.org/pdfs/consensus/algorithms_cyto_07.pdf American Society for Colposcopy and Cervical Pathology guidelines for management of abnormal Pap tests; provides detailed algorithms describing how to manage each specific Pap smear abnormality. www.cdc.gov/std/treatment The 2006 sexually transmitted infection (STI) treatment guidelines provide detailed recommendations for treatment of all sexually transmitted diseases (STDs) as well as other types of vaginitis.

467

26 CHAPT ER Contraception Adriana C. Linares and Ann I. Schutt-Ainé

Chapter contents Use of Contraception

468

History Prevalence Impediments to Access Counseling

468 468 468 468

Contraception Methods Failure Rates Medical Eligibility Criteria Barrier Contraceptives and Spermicides Fertility Awareness Methods Coitus Interruptus/Withdrawal

469 469 469 470 472 473

Among U.S. women, the prevalence of ever using a contraceptive method is almost 98% (Chandra et al., 2005). By addressing issues related to contraception at each visit, an informed family physician can help prevent complications stemming from interactions with prescribed and over-thecounter medications, as well as from the use of the contraceptive method itself.

Use of Contraception History Humans have tried to control fertility since ancient times. Egyptian papyruses describe methods to avoid pregnancy (Benagiano et al., 2006). The ancient Greeks sought to control the birth of animals using herbs, barrier methods, and other remedies (Riddle, 1999), and evidence of use of barrier methods to prevent pregnancy is found among prostitutes in France (Head, 1961). The approval of the oral contraceptive pill in the second half of the 20th century marked a great revolution in the development and widespread use of contraception methods (Winter, 1970).

Prevalence The National Survey of Family Growth found the most frequent contraception method used during the first sexual intercourse for men and women was the male condom, which is openly available in pharmacies, supermarkets, ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10026-x

Combined Hormonal Contraceptives Progestin-Only Contraceptives Intrauterine Contraceptives

Sterilization Mechanism of Action Tubal Ligation Vasectomy

Emergency Contraception Emergency Contraceptive Pills Copper-T380A Intrauterine Device

Conclusion

473 474 475

476 476 476 476

477 477 477

477

and medical offices (Chandra et al., 2005). When asked about use of current contraceptive methods, 62% of women report using a method, and in never-married cohabiting women, the most common method is the oral contraceptive pill (49%).

Impediments to Access Lack of access is an important impediment to the use of contraception. With the exception of emergency contraception, all hormonal methods in the United States are available by prescription only. More than 47 million Americans (2010) do not have health insurance and have problems accessing primary care, and even with health insurance, access to contraception may be hampered by lack of coverage. For example, in a Washington state study comparing the 91 top-selling insurance plans, almost half did not cover any contraceptive method; 37% of women had no access to sterilization; and 53% had no access to pregnancy termination (Kurth et al., 2001). Another important impediment to the use of contraception can be physician difficulty in being reimbursed for contraception services. Therefore, Table 26-1 lists common International Classification of Diseases (ICD-9) codes for contraception counseling, prescriptions, and follow-up.

Counseling When counseling patients about the use of contraception, nonjudgmental, impartial communication is best. Patients often bring experience, opinions, and some knowledge

Contraception

Table 26-1 ICD-9 Codes Used for Contraception Reimbursement

Code

Description

V25.0

General counseling and advice on contraceptive management

V25.01

Oral contraceptive initiation or counseling

V25.02

Initiation of other contraceptive method (diaphragm fitting, foam, etc)

V25.03

Encounter for emergency contraceptive counseling and prescription

V25.04

Counseling and instruction on natural family planning to avoid pregnancy

V25.09

Other family planning advice

V25.1

IUD, insertion

V25.2

Sterilization

V25.3

Menstrual extraction/regulation

V25.4

Surveillance of previously prescribed contraceptive methods

V25.40

Contraceptive surveillance, unspecified

V25.41

Repeat prescription/surveillance of OCPs

V25.42

IUD check, re-insertion or removal

V25.43

Surveillance of implantable subdermal contraceptive

V25.49

Surveillance of other prescribed contraceptive method

V25.5

Insertion of implantable subdermal contraceptive

V25.8

Post-vasectomy sperm count

V25.9

Unspecified contraceptive management

V26.4

General and counseling and advice on procreative management

V26.41

Procreative counseling and advice using natural family planning

V26.42

Other procreative management and advice

V26.5

Sterilization status

V26.51

Tubal ligation status

V26.52

Vasectomy status

V26.9

Unspecified procreative management

57170

Diaphragm/cervical cap fitting

58300

IUD insertion

58301

IUD removal

99070

Supply, diaphragm, IUD

J7300

IUD, copper (supply)

J7302

IUD, levonorgestrel (supply)

From World Health Organization (WHO). International Classification of Diseases (ICD-9). IUD, Intrauterine device; OCPs, oral contraceptive pills.

about contraception that are easily elicited by open-ended questions. From this information, counseling can be customized to fit their specific needs. Use of their own words, frequent questions and answers, and feedback from patients play an important role in future compliance with medical advice. An important consideration in contraceptive counseling is age because fertility among women varies with age. Barrier methods and some hormonal contraceptives can have low compliance in adolescents (ACOG, 2009). Older women can have more complications during pregnancy, making contraception an important component of health maintenance. Older women who are obese, smoke, or have comorbidities (e.g., hypertension, diabetes, migraines) are not good candidates to take combined hormonal contraceptives; progestin-only methods, intrauterine devices (IUDs) and sterilization may be good alternatives (Kaunitz, 2008). Women who use combined hormonal contraceptives after age 40 can be encouraged to stop in their early to mid-50s, when the likelihood of ovulation is low (ACOG, 2006). Smoking is another important variable to consider when counseling patients. All patients should be encouraged to avoid smoking or to quit if they are smoking. The use of combined hormonal contraceptives in women over age 35 who smoked more than 15 cigarettes per day is contraindicated due to the increased risk of serious cardiovascular effects (Kroon, 2007). All women should be encouraged to use condoms consistently to reduce risk of sexually transmitted infections (STIs), especially in younger women with an increased risk of STI exposure.

Contraception Methods Contraception is defined as the intentional prevention of conception or impregnation through the use of various devices, agents, drugs, sexual practices, or surgical procedures. The many methods available vary in efficacy, contraindications, and ease of use. Table 26-2 lists preferred contraceptive methods by patient type.

Failure Rates Failure rates are typically described as percentage of women experiencing an unintended pregnancy within the first year of use (Zeiman et al., 2007). Two failure rates are measured, as follows (Table 26-3): Perfect-use failure rate refers to the percentage of women who become pregnant during the first year of use when the method is used correctly and consistently according to instructions. Typical-use failure rate refers to the percentage of women who become pregnant during the first year of use, which includes both those who use the method correctly and consistently and those who do not.

Medical Eligibility Criteria The World Health Organization (WHO) periodically convenes an Expert Working Group to make evidencebased recommendations for who can safely use a 469

26

Contraception

Table 26-2 Preferred Contraceptive Options for Select Patient Groups

Patient type

Preferred options

Comments

Adolescent

DMPA, implant, COC, or IUC plus condoms

IUCs are excellent option currently underused in adolescents.

Potentially noncompliant

DMPA, implant, patch, ring, IUC

—

HIV and STD risk

Condom plus any other form of contraception

—

Postpartum and lactating

DMPA, implant, POP, IUC, LAM up to 6 months if specific criteria met

COCs can decrease quality and quantity of breast milk, but only if started before establishment of lactation.

Smoker >35 years old

DMPA, implant, POP, IUC, barrier methods

ECs contraindicated.

Diabetic

DMPA, implant, IUC, barrier methods

ECs appropriate in young normotensive well-controlled diabetic women.

Hypertensive

DMPA, implant, POP, IUC barrier methods

ECs appropriate in young well-controlled nonsmoking hypertensive women.

History of stroke/TIA

IUC, barrier methods

ECs contraindicated; may consider progestin-only methods.

History of thromboembolism

IUC, barrier methods

ECs contraindicated; may consider progestin-only methods.

Coronary artery disease

IUC, implant, barrier methods

ECs contraindicated, may consider progestin-only methods.

Mitral valve prolapse

DMPA, implant, IUC. COC; patch or ring if asymptomatic

—

Polycystic ovarian syndrome

COC, ring, patch, levonorgestrel IUC

COCs best shown to suppress androgen excess; levonorgestrel IUC provides excellent endometrial protection.

Sickle cell disease

DMPA, barrier methods

DMPA shown to decrease frequency of crises.

Gallbladder disease

DMPA, implant, IUC

COCs may accelerate progression.

Taking anticonvulsants or other hepatic inducers

DMPA, IUC

Efficacy of COCs, POPs, and implants may be reduced.

Desires long-term reversible contraception

DMPA, implants, IUC

—

Desires short-term reversible contraception

COC, POP, patch, ring, barrier methods

—

Desires convenience

DMPA, implant, IUC

—

Desires permanent contraception; no interest in future fertility

Vasectomy or tubal ligation

—

Data from World Health Organization. Medical eligibility criteria for contraceptive use 2004, and 2008 Update of the Guide (WHO website). COC, Combined (combination) oral contraceptive; DMPA, depot medroxyprogesterone acetate; IUC, intrauterine contraceptive; POP, progestin-only pill; LAM, lactational amenorrhea method; ECs, estrogen-containing contraceptives. STD, Sexually transmitted disease; HIV, human immunodeficiency virus; TIA, transient ischemic attack.

c ontraceptive method. These criteria can be found on the WHO website.

Barrier Contraceptives and Spermicides Key Points • B arrier contraceptives and spermicides create a physical barrier to fertilization. • Many of these methods are available over the counter, increasing access. • Some barriers can provide protection against cervical infections; condoms also offer protection against HIV. 470

Mechanism of Action Barrier contraceptives provide a physical barrier that prevents sperm from accessing the upper reproductive tract. They are often used in conjunction with spermicides, which act to destroy sperm and prevent fertilization.

Male Condom Materials Male condoms have been used since ancient times, with early condoms made from animal intestine. Mass production began in the 1840s with the advent of vulcanized

Contraception

Table 26-3 Failure Rates for Contraceptive Methods: Percentage of Women who Become Pregnant during First Year of Use

Women pregnant in first year

Contraceptive method

Perfect Use (%)

No method

85

Typical Use (%)

85

Barrier contraceptives and spermicides

rubber. Modern condoms are most often made of latex or polyurethane, but those made from animal intestine do still exist. Polyurethane condoms provide increased sensitivity for male partners, but the breakage and slippage rates are significantly higher (relative risk, 6.6 for breakage and 6.0 for slippage) compared with latex condoms (Frezieres et al., 1998) (Level of evidence: A). This suggests that latex condoms should be encouraged except for those with latex allergy/sensitivity.

Advantages Male condoms can decrease the transmission of STIs, including human immunodeficiency virus (HIV), when used correctly and consistently.

Male condom

2

15

Female condom

5

21

Cervical cap, nulliparous

9

16

Disadvantages

26

32

Diaphragm

6

16

Contraceptive sponge, nulliparous

9

16

Contraceptive sponge, parous

20

32

To obtain maximum protection from pregnancy and STIs, condoms must be used correctly with every act of intercourse. Those individuals with an allergy or sensitivity to latex should avoid these condoms. Some men report decreased sensitivity with condom use. A new condom must be used for each act of intercourse.

Nonoxynol-9

18

29

Cervical cap, parous

Female Condom

Fertility awareness methods Standard Days

4.75

12

TwoDay

3.5

14

Symptomothermal

2

Postovulation

1

Lactational amenorrhea

0.45

Coitus interruptus/withdrawal

4

The female condom is a thin polyurethane sheath with a ring on each end. It can be inserted into the vagina up to 8 hours before intercourse. It should not be used simultaneously with a male condom because of possible breakage or slippage of either device.

Advantages 2.45 27

Combined hormonal contraceptives Combined oral contraceptives (OCs)

0.3

8

Contraceptive patch

0.3

8

Vaginal contraceptive ring

0.3

8

Progestin-only pills (POPs)

0.3

8

Depot medroxyprogesterone acetate

0.3

3

Contraceptive Implant

0

0.1

Copper-T380A

0.6

0.8

Levonorgestrel intrauterine system

0.1

0.1

Tubal ligation

0.5

0.5

Essure

0

20%)

5 mm should be further evaluated with an endometrial biopsy (Amann et al., 2006) (SOR: B). If the endometrial sample is insufficient., the patient should be triaged to a transvaginal ultrasound in a low-risk group, with dilation and curettage for high-risk patients (Brand et al., 2000) (SOR: B).

Common Office Procedures

Cervical Polyp Removal Cervical polyps are generally benign, asymptomatic, and noted most often during a routine gynecologic examination. Most polyps arise from the endocervical mucosa, and most occur in perimenopausal women age 30 to 50. For their removal, the patient is placed in the dorsal lithotomy position and a speculum inserted vaginally. A Pap smear should be obtained and the base of the polyp identified to prevent inadvertent removal of a prolapsed endometrial polyp. The polyp is then grasped as close to its base as possible with a ring forceps and twisted. This twisting motion will dislodge the polyp, which should be sent for pathologic assessment. Hemostasis is obtained with Monsel’s solution or silver nitrate sticks if direct pressure is not sufficient. (See Tuggy Video: Polyp Removal.)

Uterine Aspiration for Biopsy or Miscarriage Management Manual vacuum aspiration (MVA) can be used in the office setting for easy sampling of the uterine endometrium with a 4-mm or 5-mm cannula when a small endometrial biopsy catheter is insufficient (Fig. 28-19). The MVA can also be used in the office for removal of retained products of conception after an incomplete or missed miscarriage up to 12 weeks without the added cost of an emergency room visit, surgical suite, and general anesthesia. The MVA device is a handheld plastic aspirator syringe attached to a plastic cannula of varying sizes. The cannula can be flexible or rigid to allow for provider preference. Vacuum aspiration is safe, quick to perform and less painful than sharp curettage and should be recommended for use in the management of incomplete abortion (Forna and Gulmezoglu, 2001). Confirmation of a non-viable pregnancy or incomplete abortion is verified with a falling serum β-hCG level, an appropriately timed ultrasound, or by clinical findings of uterine bleeding in pregnancy with significant cervical dilation in the first trimester. A blood type is obtained to determine if RhoGAM is necessary. A hematocrit may be obtained if bleeding has been significant. Once informed consent outlining the risks of bleeding, pelvic infection, uterine perforation, Asherman’s adhesions, and possible need for reaspiration is obtained, the patient may receive a sedative, analgesia, or anesthesia. Most women do well with an oral NSAID for analgesia and a paracervical block for local anesthesia. For comfort, the patient should void before the procedure. The patient is placed in the dorsal lithotomy position, and uterine size, location, and shape are assessed. A transvaginal or transabdominal ultrasound can be performed at this time to confirm findings but is not required. A speculum is placed intravaginally, vagina and cervix are cleansed, and a paracervical block is placed before the procedure. A single-toothed tenaculum is placed on the anterior cervix. The uterus is sounded to the fundus to determine intracavitary size and position. If not already dilated, the cervical os is successively dilated to a size in millimeters corresponding to the gestational age, using Denniston, Pratt, or Hegar dilators. The MVA curette is generally chosen in millimeters to correspond to the gestational age in weeks as well. Thumb buttons are used to occlude the opening to the MVA barrel, and the plunger is retracted and allowed to snap into place

Figure 28-19 The Ipas manual vacuum aspirator (MVA) is displayed with 4-mm and 5-mm cannulas used for miscarriage management in outpatient setting. Note thumb buttons that close the barrel entrance to hold negative pressure in the canister when the plunger is retracted. The buttons are then released to transfer the suction pressure to the cannula once in place.

to develop the negative pressure for suction. The cannula is attached to the MVA and placed through the cervix to the uterine fundus. The thumb buttons on each side are released, and the negative suction from the syringe is transferred to the endometrial cavity. The MVA barrel can be rotated and then brought in and out in a piston motion to dislodge the remaining products of conception. These can be observed passing through the cannula and can be evaluated fully by visual or pathologic examination after the procedure. The syringe may need to be emptied and the negative pressure reapplied based on the volume of the uterine contents. A sensation of grittiness is present in the fundus and all four uterine quadrants when the products of conception are completely removed and the cannula makes contact with the myometrium. On completion, the MVA cannula is removed from the uterus, tenaculum from the cervix, and speculum from the vagina. The patient is observed for 15 to 30 minutes to assess for excessive bleeding, hemodynamic stability, and unusual pain. Intrarectal or intravaginal misoprostol, intracervical or intramuscular methylergonovine, and intramuscular carboprost may be used for excessive bleeding. The patient may be discharged and instructed to refrain from intercourse for 2 weeks or until the bleeding resolves. She should return for excessive bleeding, significant pelvic or abdominal pain, and fever. A form of contraception is provided if the patient desires.

Breast Mass In a patient who presents with a breast mass, a careful clinical and family history with focused physical examination, a mammogram or ultrasound, and fine-needle aspiration of the mass is termed a triple test. Most primary care physicians can perform the triple test with radiologic assistance for the evaluation of a breast mass. A positive triple test (indeterminate, suspicious, or malignant) was found in 99.6% of breast cancers. On the other hand, if all three test components are negative and the patient is deemed low risk by personal or family history, the patient requires no further workup and has a less than 1% risk of cancer (National Breast Cancer Centre, 2006). 573

28


Breast Cyst Aspiration When a discrete breast mass is first discovered, a determination of solid or cystic must be made to assist with further evaluative decisions. A rapid determination can be made with one of two methods. Ultrasound can be used to identify a cystic or solid mass rapidly with minimal discomfort to the patient. If ultrasound is not available or if a therapeutic intervention is needed for drainage of a palpated cyst, a breast cyst aspiration can be performed. The patient can be placed in a recumbent position and the skin over the breast cleansed. The mass is stabilized between the thumb and index and middle fingers on the nondominant hand. Anesthesia can be used locally, but most women feel minimal discomfort. A 1.5-inch, 20- to 23-gauge needle is attached to a 10- to 30-mL syringe. The skin is punctured and the end of the needle directed into the mass with continuous suction on the syringe. The fluid of a cyst is aspirated completely before the needle is removed. Fluid should be sent for pathologic evaluation. Straw- to green-colored fluid is usually benign, and bloody brown to red fluid is more suspicious for malignancy. If bloody fluid is obtained in an atraumatic aspirate or if a lump remains, the patient should be referred for a core needle or open biopsy. (See Tuggy Video: Breast Cyst Aspiration.)

KEY TREATMENT Vacuum aspiration is safe, quick to perform, and less painful than sharp curettage and recommended in the management of incomplete abortion (Forna and Gulmezoglu, 2001) (SOR: B). The triple test of (1) careful clinical examination, (2) mammogram or ultrasound, and (3) fine-needle aspiration of a breast mass approaches the false-negative rate of surgical breast biopsy and the false-positive rate of frozen section (National Breast Cancer Centre, 2006) (SOR: B). If bloody fluid is obtained on an atraumatic breast mass aspirate or if a lump remains after drainage, the patient is referred for surgical consult for core or open biopsy (National Breast Cancer Centre, 2006) (SOR: B).

Fine-Needle Aspiration Cytology or Biopsy Fine-needle aspiration (FNA) can be performed in the office with minimal equipment for diagnosis of a discrete, solid breast mass. FNA testing results in a sensitivity of 90% and a false-negative rate of 3% to 10% in experienced hands (Valea and Katz, 2007). Contraindications include an overlying skin infection, underlying pulsatile mass, and a history of bleeding disorders. The patient is properly given informed consent. She is recumbent in position, and the area of puncture is identified, marked, and cleansed. A local injection of 1 to 2 mL of anesthetic is infiltrated into the skin over the mass. The mass is stabilized with the three-finger technique previously mentioned. A 10- to 20-mL syringe with 18- to 22-guage needle attached is advanced into the mass. Full aspiration suction is performed, and the needle is passed through the mass in different planes three to five times for an adequate sample. The suction is released and the needle removed. The cell sample, frequently only in the needle itself, is placed on a cytology slide and fixed for proper pathologic assessment. 574

FNA provides histologic diagnosis but cannot determine architectural features. FNA should not be used to investigate microcalcifications, and it cannot distinguish ductal carcinoma in situ from invasive cancer. A core or open biopsy should be performed in these patients for more definitive diagnosis before excision or definitive treatment. (See Tuggy Video: Needle Aspiration.)

Neonatal Circumcision Circumcision has been used in religious rites for centuries and was used in ancient Egypt as a method for hygiene. Modern data in the United States is conflicting as to the benefits versus risks. By age 5 years, 90% of boys have a spontaneously retractable foreskin. The incidence of phimosis decreases with age and may be treated with a steroid cream. The medical approach to phimosis is initially successful in about 80% of cases and a year later 60% had no phimosis (Ku and Huen, 2007). Many parents still elect to have their male infants circumcised. The American Urological Association revised their policy to say that circumcision should be presented for health benefits (Tobian et al., 2010). The American Academy of Pediatrics, American Medical Association, and American College of Obstetrics and Gynecology all consider the procedure elective with minimal benefits (Lannon et al., 1999). The WHO–United Nations program on HIV/AIDS concluded that male circumcision is efficacious in reducing sexual transmission of HIV from women to men. In Africa, circumcision decreased HIV acquisition by 53% to 60%. Herpesvirus type 2 is decreased by 28% to 34% and HPV prevalence by 32% to 35% in circumcised men. Among female partners of circumcised men in these African studies, the incidence of bacterial vaginosis was reduced by 40% and Trichomonas vaginalis by 48%; genital ulcers decreased as well (Tobian et al., 2010). The incidence of urinary tract infection (UTI) is reduced with circumcision in some populations. If a population has a baseline UTI incidence of 3% or higher and circumcision complication rate less than 2%, circumcision is helpful in reducing UTIs. In normal infants the risk of UTI is 1% or less, in those with prior UTI 10%, and in those with vesicoureteral reflux 30% (Singh-Grewal, 2005). The main risk is bleeding, followed by infection. Actual rates of hemorrhage in medically indicated or ritual hospital-based circumcision range from 0.2% to 3% (Bocquet et al., 2010). Although numbers may be declining in some U.S. areas, circumcision remains one of the most common procedures performed. A neonatal circumcision is normally performed at 12 to 48 hours old once the infant has stabilized after birth, but may be performed up to 4 to 6 weeks of age. Before the procedure, each patient should be examined thoroughly for signs of congenital anomalies of the penis, urethra, or urinary tract. If hypospadias is present, circumcision is stopped or not performed, to allow the tissue to be used in a corrective surgical procedure to repair the urethra and glans. Many locations recommend no oral intake for 1 hour before the procedure to prevent aspiration. Oral sucrose can be used to reduce pain during the procedure (Gatti, 2003). A dorsal penile block or penile ring block is more effective then EMLA cream or sucrose. EMLA cream provides


a nesthesia but has a risk of methemoglobinemia (BradyFryer et al., 2010). Inspect first to make sure there is no hypospadias or hidden penis. If the penis is normal and parental consent has been obtained, the infant is placed on a circumcision restraint board and the skin prepared. A dorsal block is achieved by injecting 0.4 to 0.5 mL of 1% lidocaine without epinephrine at the base of the penile shaft at both the 10 and 2 o’clock positions and 5 mm distal to the skin reflection onto the pubic area. Inject 1 to 3 mm deep under Buck’s fascia after aspirating to ensure you are not in a blood vessel. A ring block can also be done, slightly higher on the penile shaft circumferentially in the subcutaneous tissues, taking care to avoid injury to the urethra or vasculature (Fig. 28-20). Once anesthesia is complete, grasp the foreskin distally at 3 and 9 o’clock with two hemostats. All techniques require freeing of adhesions with blunt dissection, usually done with a straight Kelly clamp inserted between the foreskin and glans in a superior direction to avoid the urethra. Open the clamp and sweep laterally. Avoid the highly vascular frenulum. Free the adhesions to the coronal sulcus of the glans. Use a straight hemostat to clamp the free dorsal foreskin, again making sure the tip is held up and away from entering the urethra. Clamp three-fourths the length of the foreskin dorsally. Insert iris scissors and carefully cut the foreskin along the crushed line. Peel the foreskin back to reveal the glans. Avoid degloving the shaft and damage to the frenulum.

Gomco Clamp The Gomco is the most common circumcision clamp. Test the clamp’s fit with the base before use. Estimate the correct size so that the bell covers at least seven-eighths of the glans (1.1, 1.3, and 1.5 sizes available). The glans is then covered with the Gomco bell and the foreskin pulled over it, sometimes with the aid of a clamp or safety pin. The bell and foreskin are then pulled through the hole in the base plate and the foreskin is arranged to ensure even tissue removal. The clamp is than placed on the base plate and the bell stem hooked over the clamp bar. Once positioning is confirmed, the clamp is tightened for 5 to 10 minutes and the remaining foreskin removed with a #10 scalpel. If hemostasis is confirmed, the clamp is removed and the glans is covered regularly with petroleum jelly at each diaper change. Healing should take 4 to 10 days. Complications include bleeding, infection, and trauma to the penis. Bleeding can be controlled with silver nitrate or a simple suture if not resolved with pressure. (See Tuggy Video: Neonatal Circumcision.)

Plastibell The Plastibell device is a plastic ring on the end of a central removable post. The ring is placed between the glans and foreskin. A tight ligature of moistened suture is placed around the foreskin and tightened into a sulcus on the ring. Foreskin distal to the ring is excised and the handle of the device broken off. The plastic ring stays in place, with the ligature tied tightly around the protective ring, for 5 to 10 days and falls off spontaneously. The appearance of the small amount of necrotic skin may worry parents, and it may be

Deep dorsal vein, artery, and nerve Superficial dorsal veins Lateral superficial vein

Corpus cavernosum Corpus spongiosum

Urethra Figure 28-20 Dorsal penile block. The dorsal penile nerve is anesthetized using no more than 1.0 mL total of 1% lidocaine without epinephrine. The anesthetic is administered at the dorsum of the penis approximately 0.5 cm distal to the penile root at the 12 and 2 o’clock positions. (From Pfenninger JL, Fowler G [eds]: Procedures for Primary Care Physicians, 2nd ed. St Louis, Mosby, 2003; and Chavez MC, Maker VK. Office surgery. In Rakel RE. Textbook of Family Medicine, 7th ed. Saunders-Elsevier, Philadelphia, 2007.)

complicated with incomplete or irregular skin edges if the ligature is not tied tightly enough.

Mogan Clamp The Mogan clamp is used in traditional Jewish circumcisions and may cause less pain by being faster. The foreskin is grasped with the nondominant hand and the glans pushed downward. The foreskin is slid into the clamp from anterior to posterior, taking care not to trap the glans. The clamp opens only 3 mm to prevent major glans entrapment. Once in place and the glans is confirmed below the plate, the clamp is closed and the distal foreskin removed. The clamp is left in place for a few minutes, then removed, and the foreskin retracted over the glans.

KEY TREATMENT Oral sucrose reduces painful procedures in infants (Gatti, 2003) (SOR: A). Dorsal penile block or penile ring blocks are more effective than EMLA cream or sucrose (Brady-Fryer et al., 2010) (SOR: A). EMLA cream provides anesthesia but has a risk of methemoglobinemia (Brady-Fryer et al., 2010) (SOR: A)

Musculoskeletal Office Procedures Aspiration of Knee Joint (Arthrocentesis) The knee is one of the largest and most accessible joints for arthrocentesis or joint injection. Aspiration of joint fluid from the knee is performed to assess for infection, inflammation, 575

28


crystal deposition, or traumatic complications. Infections may show a significantly high white blood cell infiltrate with visible organisms on Gram stain. Inflammation may show the same without organisms seen. Crystal disease may show urate or calcium pyrophosphate crystals. Trauma may produce a bloody aspirate with tears of a ligament or cartilage and fat lobules with an intra-articular fracture. Prior to the aspiration, the patient is consented and placed in a recumbent position with the knee flexed slightly with a rolled towel. The knee is assessed for effusion and the aspiration site marked and cleansed with a sterilizing wash. The knee joint space can be entered with a 22-gauge needle on a syringe on either side, but usually from the lateral aspect 1 cm lateral and superior to the patella, and directed 45 degrees downward angling under the patella, with aspiration done during insertion. When the joint space is entered, fluid should enter the syringe rapidly. Milking the lateral and medial recesses of the knee toward the needle tip will remove more fluid. The needle is removed after aspiration, or it is left in place and the syringe changed under sterile conditions for a steroid injection to follow, if necessary. Large joints can be injected with 20 to 40 mg of triamcinolone or 6 to 12 mg of betamethasone with 3 to 6 mL of 1% lidocaine for inflammatory conditions unrelated to infections. Procedural risks include septic arthritis, mild injury to the

articular cartilage, and hemarthrosis. (See Tuggy Video: Knee Aspiration.)

Shoulder Injection The subacromial bursa is another location frequently treated with steroid injection for bursitis or tendonitis. Injections of 10 to 20 mg of triamcinolone with 2 to 4 mL of lidocaine can be performed into the subacromial bursa. The easiest approach to the subacromial space is with the patient seated comfortably and arms resting at the side. The lateral shoulder is prepared with a sterile solution after palpating landmarks. The acromial process is identified on the lateral shoulder above the humeral head. In the sulcus between the humeral head and the acromial process lies the subacromial bursa. Marking the lateral border of the acromial process can provide some assistance. A 22- to 25-gauge needle on a syringe with the injection is then aimed directly into the sulcus between the bones 1 cm below the acromial process perpendicularly through the deltoid muscle. Ligamentous or muscular structures will resist injection, but the bursa should allow free infusion. Relief of pain may be noted in a few minutes if lidocaine is used and confirms the injection was placed appropriately. (See Tuggy Video: Joint Injection—Shoulder.)


Web Resources www.cdc.gov/rabies/exposure/postexposure.html Centers for Disease Control and Prevention website has advice on rabies prophylaxis for animal bites. www.cdc.gov/mmwr/preview/mmwrhtml/rr5011a1.htm#tab3 CDC website has details from the 2001 postexposure prophylaxis (PEP) guidelines. www.mdconsult.com/das/book/body www.npinstitute.com Postgraduate procedural skills training.

576

www.proceduresconsult.com/medical-procedures/ Procedural training and videos. www.nejm.org/multimedia/medical-videos Procedural education and videos. http://emedicine.medscape.com/clinical_procedures Information on additional procedures, including those covered in this chapter www.mpcenter.net/ Excellent patient education materials.

C H A P T ER

29

Sports Medicine Jonathan A. Drezner, Kimberly G. Harmon, and John W. O’Kane

Chapter contents Preparticipation Physical Evaluation Warning Symptoms in Athletes Limitations of Cardiovascular Screening

Cardiac Disorders in Athletes Arrhythmias Sudden Cardiac Death Automated External Defibrillators in Athletic Medicine

Concussion in Sports

578 579 579

580 580 581 582

582

Symptoms and Incidence Sideline Management Return to Play

582 583 583

Cervical Spine Injuries Strains and Sprains Stingers Cervical Cord Neurapraxia Catastrophic Cervical Spine Injury

Environmental Influences Exertional Heat Illness Exertional Hyponatremia Cold Injury

Sports Trauma to the Teeth, Face, and Eyes Dental Trauma Facial Trauma Eye Trauma

Infectious Disease Mononucleosis

Sports Dermatology Fungal Infections Viral Infections Bacterial Infections

Exercise-Induced Bronchospasm Pneumothorax

Hematologic Problems Sports Anemia Exertional Hemolysis Iron Deficiency Anemia Low Ferritin in Nonanemic Athlete Sickle Cell Trait and Sudden Death

592 592 593

593 593 593 593 593 594

Gastrointestinal Problems

594

Genitourinary Problems

594

584

Low Back Pain

594

584 584 585 585

Spondylolysis

594

Muscle and Tendon Injuries

594

586 586 586 587

588 589 589 589

590 590

Mechanism of Injury Histopathology Muscle Strains Tendinopathy

Shin Pain Medial Tibial Stress Syndrome Chronic Exertional Compartment Syndrome

594 595 595 595

596 596 596

Stress Fractures

597

The Pediatric Athlete

597

Physeal and Apophyseal Injuries

Special Concerns for the Female Athlete

598

598

591 591 591 592

Sports medicine involves the care of patients with illnesses and injuries related to sports and exercise. Both orthopedic and medical conditions affect a wide spectrum of patients during sports and recreational activities. The field of primary care sports medicine has emerged over the last 30 years as a leader in the comprehensive care of athletes, teams, and exercising individuals. Although sports medicine is often viewed in the context of professional and elite athletes, the principles and practice of sports medicine apply to athletes of all levels and ages. The role of a sports medicine physician is to promote the health and safety of exercising individuals, prevent injury and illness, optimize function, and minimize disability that would preclude sports participation. Sports medicine physicians work ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10029-6

Pulmonary Problems

closely with a multidisciplinary team of health care providers (specialty physicians and surgeons, athletic trainers, physical therapists, nutritionists, psychologists, and conditioning coaches) to satisfy the complete medical needs of athletes. Sports medicine includes a rapidly expanding core of knowledge related to medical issues in sports and exercise for which the primary care sports medicine physician is uniquely trained. Primary care sports medicine is a subspecialty designation obtained through completion of an accredited sports medicine fellowship and passing the Certificate of Added Qualification examination. Many practicing primary care providers also gain vast experience in sports medicine through office treatment of orthopedic injuries, event coverage, and preparticipation screening evaluations.

29

Sports Medicine

usculoskeletal problems account for up to 20% of all priM mary care office visits (Urwin et al., 1998; Woodwell and Cherry, 2004), and approximately 90% of all sports injuries are treated nonsurgically. Thus, a sound clinical foundation in the evaluation and treatment of musculoskeletal disorders is critical to primary care providers and helps guide appropriate referral to orthopedic and rehabilitative specialists. This chapter focuses on both the medical aspects of sports medicine and common orthopedic injuries in athletes. Detailed reviews cover the preparticipation physical evaluation, cardiac disorders in athletes, concussion assessment and management, cervical spine injuries, on-the-field assessment of the injured athlete, facial trauma, environmental influences such as exertional heat illness, common infections in athletes, and a systems-based review of dermatologic, pulmonary, hematologic, gastrointestinal, and genitourinary disorders in athletes. Orthopedic areas common in primary care sports medicine are also included, such as athletic low back pain, muscle strains, tendinopathy, shin pain, stress fractures, and issues unique to the pediatric or female athlete. See Chapters 30 and 31 for a comprehensive review of additional musculoskeletal problems relevant to sports medicine and the care of exercising individuals.

Preparticipation Physical Evaluation Key Points • T he primary objective of the preparticipation physical evaluation is to detect preexisting medical or musculoskeletal conditions that predispose an athlete to injury, disability, or catastrophic injury. • Syncope that occurs during exercise is a serious warning sign and warrants a comprehensive cardiology evaluation to rule out an underlying cardiac disorder that predisposes to sudden death. • Any athlete with a systolic murmur of grade 3/6 in severity, a murmur that gets louder with a Valsalva maneuver or on standing (suspicious for hypertrophic cardiomyopathy), a diastolic murmur, a family history of premature sudden cardiac death, or concerning exertional symptoms should be further evaluated by a cardiovascular specialist.

A preparticipation physical evaluation (PPE), or “sports physical,” is frequently required for medical clearance before participation in organized sports. The Preparticipation Physical Evaluation monograph, first introduced in 1992, provides recommendations for the content and format of the evaluation (AAFP et al., 2005). The third edition of the monograph, updated in 2005, is supported by six national medical societies: American Academy of Family Physicians (AAFP), American Academy of Pediatrics, American College of Sports Medicine, American Medical Society for Sports Medicine, American Orthopaedic Society for Sports Medicine, and American Osteopathic Academy of Sports Medicine. The fourth edition published in 2010 also includes collaboration with the American Heart Association (AHA) regarding the preparticipation cardiovascular evaluation. The primary objectives of the PPE include the following: 1. Detection of potentially life-threatening or disabling medical or musculoskeletal conditions before athletic clearance. 2. Identification of preexisting conditions that may predispose athletes to injury. 578

3. Satisfying legal or administrative requirements. Secondary objectives of the PPE include the following: 1. Promoting the health and safety of athletes in training and competition. 2. Serving as an entry point into the health care system for adolescents. 3. Providing an opportunity for a general health assessment. The recommended frequency of the PPE varies widely according to the requirements of the specific school, organization, or state. AHA first published consensus recommendations for cardiovascular screening in athletes in 1996 and reaffirmed these recommendations in 2007, which have influenced the format and timing of the PPE (Maron et al., 1996b, 2007). A comprehensive PPE is recommended on entry into middle school, high school, and college before participation in competitive sports. For youth and high school athletes, a comprehensive PPE should be repeated every 2 years. For years not requiring a comprehensive PPE, annual updates consisting of a comprehensive history and determination of height, weight, and blood pressure, along with a problem-focused evaluation of new concerns, illnesses, or injuries, should occur on interval years for youth and high school athletes and on all subsequent years for college athletes. The PPE history focuses on symptoms related to exercise, such as exertional syncope, lightheadedness, chest pain, palpitations, dyspnea, wheezing, or fatigue with less than expected activity (Box 29-1). A past medical history of preexisting cardiac or pulmonary conditions, murmurs, hypertension, coronary artery disease risk factors, asthma, concussions, illicit drug use, prior orthopedic injuries, or other medical conditions that place an athlete at risk of injury should be noted. Specific questions to identify a family history of premature death, cardiovascular disease, and hereditary cardiac disorders, such as hypertrophic cardiomyopathy, Marfan’s syndrome, and long QT syndrome, are also recommended. The PPE examination consists of both medical and musculoskeletal components. The cardiovascular examination is a major focus of the medical evaluation and consists of a blood pressure measurement, palpation of the radial and femoral artery pulses, cardiac auscultation with the patient both supine and standing, and recognition of the physical manifestations of Marfan’s syndrome (Maron et al., 1996b; Maron et al., 2007). Any heart murmur detected should be further assessed during the Valsalva maneuver or while moving the patient from a squatting to a standing position. These maneuvers decrease venous return and may accentuate the murmur of hypertrophic cardiomyopathy, the leading cause of sudden cardiac death in young athletes. However, hypertrophic cardiomyopathy is difficult to detect on examination alone because outflow tract obstruction, which causes the harsh systolic murmur, is present in only about 25% of patients with the disorder (Maron, 1997) (Fig. 29-1). The musculoskeletal assessment serves as a screening evaluation of the spine and upper and lower extremities. Joint range of motion, strength, and stability should be tested. Several functional tests, such as hopping, squatting, and “duck walking,” assess many anatomic areas at once and make the evaluation more efficient. Previous orthopedic injuries can also be evaluated in more detail to detect problems that require further rehabilitation or protective bracing before sports participation.

Sports Medicine

Box 29-1 Preparticipation Physical Evaluation (PPE): Cardiovascular History Questions • • • • • • • • • •

ave you ever passed out or nearly passed out during or after exercise? H Have you ever had discomfort, pain, pressure, or tightness in your chest during exercise? Do you get lightheaded or feel more short of breath than expected during exercise? Does your heart ever race or skip beats (irregular beats) during exercise? Has a doctor ever told you that you have a heart problem, high blood pressure, high cholesterol, a heart murmur, a heart infection, Kawasaki’s disease, or an unexplained seizure disorder? Has a doctor ever ordered a test for your heart, for example, an ECG or echocardiogram? Has any family member or relative died of heart problems or had an unexpected or unexplained sudden death before age 50 (including drowning, motor vehicle crash, or sudden infant death syndrome)? Has anyone in your family had unexplained fainting, seizures, or near-drowning? Does anyone in your family have a heart problem, pacemaker, or implanted defibrillator? Does anyone in your family have hypertrophic cardiomyopathy, Marfan’s syndrome, arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, short QT syndrome, Brugada syndrome, or catecholaminergic polymorphic ventricular tachycardia?

A

B

Figure 29-1 Hypertrophic cardiomyopathy. A, Gross appearance; B, histologic appearance. Note the myocardial fiber disarray. (From Braunwald E. Essential Atlas of Heart Diseases, 3rd ed. Philadelphia, Current Medicine, 2000.)

Warning Symptoms in Athletes Warning or “red flag” symptoms that may indicate the presence of an underlying cardiovascular disorder should be recognized and further assessed before medical clearance. Syncope that occurs during but not after exercise is of great concern and warrants a comprehensive cardiology evaluation to rule out the presence of an occult cardiac disorder that may lead to sudden death. Other worrying symptoms include palpitations, chest pain, lightheadedness, and fatigue or dyspnea greater than expected for the level of activity. Athletes with warning symptoms should be evaluated by an electrocardiogram (ECG), echocardiogram, and exercise stress test and referred to a cardiologist. In addition, systolic murmurs of grade 3/6 in severity, all diastolic murmurs, any murmur that becomes louder with a Valsalva maneuver or on standing (suspicious for hypertrophic cardiomyopathy), and a concerning family history of premature sudden cardiac death or hereditary cardiac disorder should be further evaluated by a cardiovascular specialist. If a cardiac abnormality is identified, the decision to withhold medical clearance for participation in competitive sports is difficult and should be carefully considered on an individual basis. The American College of Cardiology 36th

Bethesda Conference defined eligibility recommendations for athletes with cardiovascular abnormalities (Maron and Zipes, 2005).

Limitations of Cardiovascular Screening Despite efforts to standardize the format and approach to the PPE, several limitations of the screening process still exist. In 2007, only 19% of U.S. states used forms that were considered adequate by AHA, and 35% of states allowed practitioners with limited cardiovascular training to perform the evaluation (Glover et al., 2007). Unfortunately, recommendations to use a comprehensive personal and family questionnaire to guide the PPE are not widely adopted, and recommended screening protocols are often incompletely or inadequately implemented. In addition, the PPE is screening for medical conditions that place an athlete at increased risk of sudden death, and no outcomes-based research has demonstrated that the PPE is effective in preventing sudden death or potentially catastrophic events, or for identifying athletes at risk. A complicating feature of the screening process is that athletes who harbor underlying structural heart disease may be asymptomatic until the sudden cardiac arrest. In a review of 134 cases of sudden cardiac death, only 579

29

Sports Medicine

18% of athletes had symptoms of cardiovascular disease in the 3 years before their death, and only 3% were suspected of having a cardiovascular condition after PPE (Maron et al., 1996a). Limitations in the traditional screening process have led to widespread debate regarding the addition of noninvasive cardiovascular screening techniques, such as electrocardiography (ECG), to the PPE. In 2007, AHA reaffirmed recommendations against universal ECG screening in athletes, citing a low prevalence of disease, poor sensitivity, high false-positive rate, poor cost-effectiveness, and a lack of clinicians to interpret the results (Maron et al., 2007). In contrast, the European Society of Cardiology, International Olympic Committee, and the governing associations of several U.S. and international professional sports leagues endorse the use of ECG in the screening of athletes (Corrado et al., 2006; Ljungqvist et al., 2009). These recommendations are supported by studies showing that ECG is more sensitive than history and physical examination alone in identifying athletes with underlying cardiovascular disease, including a 77% greater power to detect hypertrophic cardiomyopathy (Corrado et al., 1998). In 2006, Corrado and associates reported results from screening 42,386 athletes over 25 years from the national PPE program in Italy. Disqualification on the basis of a screening protocol using history, physical examination, and ECG produced a 10-fold reduction in the incidence of sudden cardiac death in young competitive athletes and an 89% reduction of sudden death from cardiomyopathy. Although only 0.2% of athletes were disqualified for potentially lethal cardiovascular conditions, the study reported a 7% false-positive rate and a 2% overall disqualification rate. This raised concerns that adopting such a program in the United States would lead to an unacceptable number of disqualifications in athletes with a low risk of sudden death. Complex issues regarding feasibility, cost-effectiveness, appropriate physician, and healthy system infrastructure remain before large-scale implementation of ECG screening in the United States can be considered. However, some physicians are using ECG during PPE to improve detection of potentially lethal cardiovascular abnormalities. When used, ECG interpretation must be based on modern criteria to distinguish abnormal findings from physiologic alterations in athletes, to ensure acceptable accuracy and a low false-positive rate (Drezner, 2008). In a study of 2720 competitive athletes and physically active schoolchildren, a U.K. study reported a false-positive rate of 3.7% using history, physical examination, and ECG, with only 1.9% of falsepositive results determined by ECG alone (Wilson et al., 2008). Nine athletes (0.3% of those screened) were found to have a cardiovascular condition known to cause sudden cardiac death in young persons, and all athletes were detected by ECG, not by history or physical examination. Physicians interpreting ECGs in athletes should be familiar with common training-related ECG alterations that are normal variants. In contrast, training-unrelated ECG changes suggest the possibility of underlying pathology, require further diagnostic workup, and should be considered abnormal. Current recommendations for ECG interpretation in athletes to distinguish pathologic ECG abnormalities from physiologic ECG alterations have been recently provided (Corrado et al., 2009). 580

Cardiac Disorders in Athletes Key Points • B radyarrhythmias caused by increased resting vagal tone are common in athletes and include sinus bradycardia, sinus arrhythmia, first-degree atrioventricular block, and Wenckebach (Mobitz I) second-degree AV block. • Mobitz II second-degree and complete third-degree AV blocks are always pathologic and warrant cardiologic evaluation. • Supraventricular tachyarrhythmias in the athlete are abnormal and require further evaluation and treatment, often with radiofrequency ablation, before participation in strenuous exercise. • Ventricular arrhythmias are life-threatening events and usually occur in the presence of structural heart disease or ion channel disorders. • Hypertrophic cardiomyopathy, coronary artery anomalies, and commotio cordis are the most common causes of sudden cardiac death in young U.S. athletes.

Arrhythmias Cardiac arrhythmias in athletes range from benign to life threatening. Bradyarrhythmias are more common in athletes than in the general population because of an increase in resting vagal tone as a response to regular strenuous exercise. Common bradyarrhythmias include sinus bradycardia, sinus arrhythmia, first-degree atrioventricular (AV) block, and Wenckebach (or Mobitz I) second-degree AV block (Huston et al., 1985; Link et al., 2001). These bradyarrhythmias are usually asymptomatic and should resolve during exercise by the withdrawal of vagal tone and associated catecholamine influx. Athletes with symptomatic Wenckebach block, such as presyncope or syncope during exertion, require further evaluation by a cardiologist and often placement of a permanent pacemaker and restriction of activities. Higher degrees of heart block, such as Mobitz II second-degree and complete third-degree AV blocks, are always pathologic in any individual, including athletes (Fig 29-2). Mobitz II and complete heart blocks signify marked disease in the His-Purkinje system and are generally accepted as a class I indication for permanent pacemaker placement, even in the absence of symptoms (Link et al, 2001). Tachyarrhythmias in the athlete are abnormal and require further evaluation and treatment before participation in strenuous exercise. The treatment of many supraventricular

monitor P

P

P

P

T Figure 29-2 Mobitz II second-degree atrioventricular block. Note that every alternate P wave is blocked. (From Goldberger E. Treatment of Cardiac Emergencies, 5th ed. Philadelphia, Saunders, 1990.)

Sports Medicine

tachyarrhythmias has been greatly advanced by the use of radiofrequency (RF) ablation, which might offer an actual cure and obviate the need for lifelong pharmacologic treatment. The most common tachyarrhythmia in athletes is atrial fibrillation (AF). Studies have suggested that AF occurs more frequently in athletes than in the general population (Furlanello et al., 1998; Huston et al., 1985). This might be a consequence of increased vagal tone and bradycardia in athletes, which allows dispersion of atrial repolarization and results in a higher susceptibility to AF. Radiofrequency ablation is curative in most cases of paroxysmal AF (Link et al., 2001). If pharmacologic treatment is needed, rate control can be accomplished with beta-adrenergic blockers or calcium channel blockers, and anticoagulation should be considered with aspirin or warfarin, depending on the frequency of AF and other risk factors for thromboembolism. Any athlete receiving anticoagulation therapy with warfarin should be restricted from sports involving collision or bodily contact. Atrioventricular nodal reentrant tachycardia (AVNRT) is characterized by abrupt onset and termination of symptoms, a narrow QRS complex, and no evidence of atrial activity on the ECG during the tachycardia. AVNRT caused by an accessory bypass tract, known as Wolff-Parkinson-White (WPW) syndrome, may be evident on the ECG by the characteristic delta wave (slurred upstroke of QRS complex), short PR interval, and prolonged QRS complex (Fig. 29-3). Athletes with WPW may be at risk of sudden death and should be strongly considered for RF ablation. Radiofrequency ablation for both AVNRT and WPW offers cure rates higher than 95% (Link et al., 2001; Manolis et al., 1994). Atrial flutter is an unusual arrhythmia in trained athletes and typically results from an underlying cardiomyopathy.

Ventricular tachyarrhythmias in athletes are life threatening and usually the result of structural heart disease such as hypertrophic cardiomyopathy, anomalous coronary artery, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia (ARVD), or atherosclerotic coronary artery disease (CAD). Ventricular arrhythmias and sudden death may also occur in individuals with structurally normal hearts. This may occur from ion channel disorders, such as long QT syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome, or from commotio cordis. Long QT syndrome is characterized by a prolonged QTc interval, and Brugada syndrome is suggested by an incomplete right bundle branch block and ST-segment elevation in the precordial leads. Exercise may provoke ventricular arrhythmias because of high catecholamine levels and make ventricular fibrillation more difficult to terminate. Athletes who experience a resuscitated sudden death should undergo an extensive workup and treatment with an implantable cardioverter-defibrillator (Link et al., 2001).

Sudden Cardiac Death Sudden cardiac death in athletes is a catastrophic event and the leading cause of death in exercising young athletes (Maron et al., 2009) The estimated incidence of sudden cardiac death in high school and college athletes is 1 in 100,000 to 200,000 athletes per year (Maron et al., 2009; van Camp et al., 1995). However, these studies are limited by the lack of a mandatory reporting system for juvenile sudden death and their reliance on electronic databases and media reports to identify cases of sudden death. Thus, current reports likely underestimate the true incidence of sudden cardiac death in athletes.

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Figure 29-3 Atrioventricular nodal reentrant tachycardia. Notice the characteristic triad of the Wolff-Parkinson-White (WPW) pattern: wide QRS complexes, short PR intervals, and delta waves (arrows) that are negative in some leads (e.g., II, III, aVR) and positive in others (aVL and V2 to V6). The Q waves in leads II, III, and aVF are the result of abnormal ventricular conduction (negative delta waves) rather than an inferior myocardial infarction. This pattern is consistent with a bypass tract inserting into the posterior wall of the left ventricle. (From Goldberger AL. Clinical Electrocardiography: a Simplified Approach, 7th ed. Philadelphia, Saunders-Elsevier, 2006.)

581

29

Sports Medicine

Box 29-2 Causes of Sudden Cardiac Death in Young Athletes

Structural Hypertrophic cardiomyopathy (HCM)* Coronary artery anomalies Aortic rupture/Marfan’s syndrome* Dilated cardiomyopathy (DCM)* Myocarditis Left ventricular outflow tract (LVOT) obstruction Mitral valve prolapse (MVP) Coronary artery [atherosclerotic] disease (CAD)* Arrhythmogenic right ventricular cardiomyopathy (ARVC)* Postoperative congenital heart disease

r esuscitation (CPR) and prompt defibrillation with an AED were provided (Drezner et al., 2009). Comprehensive emergency response planning is needed to ensure an efficient and structured response to sudden cardiac arrest in the athletic setting. This includes establishing a communication system to activate the emergency medical services (EMS) system and alert any on-site response team, training of anticipated responders (e.g., coaches) in CPR and AED use, access to an AED, and practice and review of the response plan. High suspicion of sudden cardiac death should be maintained in any collapsed and unresponsive athlete, with application of an AED as soon as possible for rhythm analysis and defibrillation if indicated (Drezner et al., 2007).

Electrical Long QT syndrome (LQTS)* Wolff-Parkinson-White syndrome (WPW) Brugada syndrome* Catecholaminergic polymorphic ventricular tachycardia (CPVT)* Short QT syndrome* Complete heart block (CHB)

KEY TREATMENT High suspicion of sudden cardiac arrest should be maintained in any collapsed and unresponsive athlete, with application of an automated external defibrillator (AED) as soon as possible for rhythm analysis and defibrillation if indicated (Drezner et al., 2007, 2009) (SOR: B).

Other Drugs and stimulants Commotio cordis Primary pulmonary hypertension (PPH)*

Concussion in Sports Key Points

*Familial/genetic etiology.

The cause of sudden cardiac death in young athletes (35), atherosclerotic CAD accounts for more than 75% of cases of sudden cardiac death.

Automated External Defibrillators in Athletic Medicine Limitations of the cardiovascular screening process, the overwhelming desire to protect young athletes from a tragic event, and the success of early defibrillation programs (Caffrey et al., 2002; Page et al., 2000; Valenzuela et al., 2000) using accessible automated external defibrillators (AEDs) have propelled the placement of AEDs into the athletic setting (Drezner et al., 2005). Recent research suggests an improved survival rate for young athletes with sudden cardiac arrest if early defibrillation is achieved. A retrospective cohort of 1710 U.S. high schools with an on-site AED program found 14 cases of sudden cardiac arrest in high school studentathletes and a 64% survival rate if early cardiopulmonary 582

• C oncussion is a neurologic disturbance with variable symptoms, including confusion, headache, vision problems, nausea, balance problems, amnesia, and loss of consciousness. • Concussion assessment includes evaluation of cranial nerves, pupillary dilation and reactivity, balance and coordination, motor strength, and cognitive function. • A player should never return to play while symptomatic from a concussion. • Once asymptomatic, athletes should follow a stepwise and graded exercise program before return to play. • Neuropsychological testing can aid return-to-play decisions for complex concussions.

In 1966 the Congress of Neurological Surgeons proposed a consensus definition of concussion. Since then, both the definition and our understanding of concussion have been evolving. A concussion is defined as a traumatically induced transient disturbance in neurologic function, usually caused by a direct blow to the head, neck, or face (Aubry et al., 2002).

Symptoms and Incidence A concussion usually results in the rapid onset of brief neurologic impairment that resolves spontaneously. Symptoms of concussion include loss of consciousness, amnesia, confusion, headache, vision problems, nausea, and balance problems (Box 29-3). A concussion may or may not be associated with a loss of consciousness. Over 90% of concussions are not associated with a loss of consciousness, and unconsciousness is not a marker of the severity of the injury (Lovell et al., 1999). Amnesia can include loss of memory of the events before (retrograde amnesia) or

Sports Medicine

Box 29-3 Signs and Symptoms of Concussion Disorientation Confusion Amnesia Loss of consciousness Headache Dizziness Balance problems Poor coordination, gait Nausea, vomiting Visual problems (flashing lights) Hearing problems (tinnitus)

Feeling “foggy” or “dazed” Inability to focus Difficulty concentrating Irritability Emotional lability Excessive drowsiness Delayed verbal or motor response Vacant, “glassy” stare Slurred, incoherent speech Decreased playing performance Seizure (rare)

after (posttraumatic amnesia) the concussion, or both, and amnesia appears to be the best predictor of severity in athletic concussion (Collins et al., 2003). Conventional imaging studies such as computed tomography (CT) or magnetic resonance imaging (MRI) are normal in concussion, indicating that concussion is a functional rather than a structural injury (McCrory, 2001). An estimated 300,000 concussions occur each year from sports-related activity (Centers for Disease Control and Prevention [CDC], 1997). In high school football, there are 40,000 concussions per year, for a 3% to 5% incidence (Powell and Barber-Foss, 1999). High-risk sports include contact and collision sports such as football, ice hockey, rugby, wrestling, and to a lesser extent, soccer and basketball. Women may be more prone to concussion in some sports (Tierney et al., 2005), for unclear reasons, with further research needed. Younger players also may be more prone to concussion because of less developed neck muscles and the higher relative weight of the head compared with the rest of the body. In addition, children may sustain more serious concussions because of their immature nervous system.

Sideline Management When attending to an athlete on the field with a suspected concussion, attention must first be given to basic first aid. Airway, breathing, and circulation (ABCs) and level of consciousness should be initially assessed, followed by an evaluation for potential cervical spine injuries. If loss of consciousness has occurred, the duration of unconsciousness should be determined. A brief loss of consciousness is generally defined as less than 30 to 60 seconds. If a player is unconscious for more than 30 to 60 seconds or still unconscious by the time a physician reaches the athlete on the field, most would consider this “prolonged.” Patients with concussions involving prolonged loss of consciousness, suspected cervical spine injuries, or gross neurologic impairment should be stabilized and transported to a hospital for further evaluation (see Cervical Spine Injuries: On-the-Field Assessment). After it is determined that the athlete is stable and safe to be moved, further assessment can take place on the sideline. Physical examination should include evaluation of cranial nerves, pupillary dilation and reactivity, balance and coordination, motor strength, and cognitive function. Orienta-

tion to time, place, and person is an incomplete assessment of cognitive function in the sports setting. Memory and recall testing, serial 7s (counting backward by 7 from 100), serial 3s (counting backward by 3 from 100), and listing the months of the year backward and forward are simple sideline tests of cognitive function. Several sideline assessment tools exist to aid medical professionals in the evaluation of an athlete with concussion. The Standardized Assessment of Concussion (SAC) is a validated sideline assessment tool, and the most recent consensus conference on concussion recommended a modified and expanded tool, the Sport Concussion Assessment Tool (SCAT2) (McCrea et al., 1997; McCrory et al., 2009). This includes a symptom scale, standard cognitive assessment, and guided physical examination. Such standardized examinations are useful for serial follow-up and if different medical personnel will be evaluating the athlete. It is important to reassess concussed athletes frequently to monitor for resolution of symptoms or signs of deterioration.

Return to Play Return-to-play decisions are driven by the concern of preventing potential complications, primarily second-impact syndrome and permanent neurologic deficit. Second-impact syndrome occurs when a player returns to play following a first concussion before the symptoms have completely resolved, and a second, often minor, blow to the head is sustained, which leads to diffuse cerebral swelling, brainstem herniation, and death. The risk for catastrophic injury in athletes returned to play while still symptomatic is of particular concern in children and adolescents. Long-term cognitive deficits from concussion or repetitive blows to the head are also a concern. Repetitive concussions, especially if severe, might put athletes at risk for permanent neurologic deficits (Guskiewicz et al., 2003). However, no evidence indicates that repetitive nonconcussive blows, such as those sustained from heading a soccer ball, lead to shortterm or long-term neurologic impairment. Most concussion guidelines designed to facilitate returnto-play decisions rely on loss of consciousness and the presence of amnesia to grade the severity of the concussion. This approach makes their usefulness limited because most sports-related concussions do not involve loss of consciousness or amnesia. Current recommendations suggest that management of concussion be based on symptoms and severity. The mildest concussion is one that involves transient symptoms that resolve quickly. More severe concussions involve persistent or prolonged symptoms and cognitive deficits on neuropsychological testing. Management of concussion includes both physical and mental rest, until all symptoms have cleared, and the neurologic examination, followed by a graded and stepwise program of exertion before return to sport (Box 29-4). Repetitive concussions, which take longer to return to baseline or that occur with progressively less trauma, are also considered of greater severity. Complex or recurrent concussions with persistent cognitive impairment, neurologic findings on examination, or prolonged symptoms may warrant advanced imaging and formal neuropsychological testing and should be managed by physicians with specific expertise in sports-related concussion. 583

29

Sports Medicine

Box 29-4 Graded Return to Play after Concussion* 1. 2. 3. 4. 5. 6. 7.

est until asymptomatic R Light aerobic exercise (stationary cycling, slow jogging) More strenuous aerobic training (running, sprinting) Sport-specific training Noncontact drills Full contact drills Return to competition

Modified from McCrory P, Johnston K, Meeuwisse W, et al. Summary and agreement statement of the 2nd International Conference on Concussion in Sport, Prague, 2004. Br J Sports Med 2005;39:196-204. *A player should never return to play while symptomatic from a concussion. In this supervised stepwise progression, the athlete can proceed to the next level if asymptomatic at the current level. If any postconcussion symptoms occur, the athlete should return to the previous asymptomatic level and try to progress again after 24 hours. Athletes with simple concussions may progress through these stages over several days. In cases of complex concussion, recovery is more prolonged.

Neuropsychological testing in concussion, initially a comprehensive battery of conventional written tests administered by a trained neuropsychologist, has evolved into a variety of computer assessment tools. These neuropsychological assessment tools are gaining acceptance in high-risk sports at the collegiate and professional levels and are most useful when there is a baseline assessment done before injury. Widespread use of these tests in youth and high school sports with limited budgets and medical personnel might not be practical. In summary, concussion is a common injury in sport, and athletes sustaining a concussion should be medically evaluated by a physician. No symptomatic athlete should be allowed to return to play, and an athlete should not be allowed to return to play in the same game or practice during which an injury has occurred. Once asymptomatic, athletes should follow a graded program before return to play. Referral should be considered in complex or complicated concussions. Further research is needed to provide evidenced-based return-to-play guidelines and preventive strategies.

KEY TREATMENT A player with a concussion who is still symptomatic should be held from practice and competition and should not return to the field of play. Once asymptomatic, athletes should follow a stepwise and graded exercise program before a return to sport. (SOR: C; McCrory et al., 2009).

Cervical Spine Injuries Key Points • “ Stingers” result from a blow to the neck and shoulders with transient unilateral upper extremity pain and paresthesias resolving in minutes. 584

KEY TREATMENT Axial loading is the most common mechanism for catastrophic injury to the cervical spine during sports competition. Any athlete with significant neck or spine pain, diminished level of consciousness, or significant neurologic deficits should be immobilized and prepared for transport. Unconscious athletes are presumed to have unstable spine injuries until proven otherwise. The football helmet in a downed player wearing shoulder pads should not be removed to avoid hyperextension of the neck and secondary injury to the cervical spine.

Strains and Sprains Most sports-related neck injuries are mild and self-limiting. Patients with muscle strains and ligament sprains typically present with minor complaints and no neurologic symptoms. More significant injury should be suspected in the presence of significant cervical muscle spasm, tentative active range of motion (ROM), severe pain, or abnormal neurologic signs. Evaluation includes active cervical ROM and strength testing of the neck and upper extremities. Manual compression and axial loading to the cervical spine (Spurling’s maneuver) should not cause pain or radicular symptoms and is helpful in ruling out more significant injury (Magee, 1997). The athlete is cleared to return to play when full pain-free ROM and normal strength of the cervical spine are restored.

Stingers Stingers or “burners” are characterized by transient unilateral upper extremity pain and paresthesias resulting from a blow to the neck and shoulders. Stingers are common in American football and have been reported in up to 50% to 65% of college players (Clancy et al., 1977; Sallis et al., 1992). Stingers are peripheral nerve injuries and are considered a transient neurapraxia of the cervical nerve roots, usually involving the upper trunk of the brachial plexus (C5-C6). Stingers typically manifest with dysesthesia (burning pain) that begins in the shoulder and radiates down the arm. They often are associated with transient numbness or weakness, and all symptoms typically resolve in minutes. Stingers can occur from a tensile or compression overload (Watkins, 1986). In most high school athletes, the mechanism of injury involves a tensile or traction injury when the involved arm and the neck are stretched in opposite directions. This occurs when the neck is forcibly flexed away while the shoulder is depressed. In college and professional athletes, who have a higher likelihood of degenerative changes of the cervical spine, a compression mechanism is more likely. This involves a pinch of the cervical nerve root within the neural foramen as the neck is forcibly extended in a posterolateral direction (Levitz et al., 1997). Stingers are always unilateral, a distinguishing feature from spinal cord injuries, which involve symptoms in multiple limbs. Athletes are safe to return to play when symptoms have fully resolved and the athlete can demonstrate full cervical ROM and a normal neurologic examination.

Sports Medicine

Radiography and MRI should be considered in athletes with recurrent stingers to evaluate for cervical degenerative disk disease (Levitz et al., 1997). Rarely, more significant nerve injury involving axonotmesis (axon disruption) occurs, causing persistent weakness. Athletes with significant weakness 24 to 48 hours after injury may benefit from treatment with a short burst of oral corticosteroids. If weakness persists, electromyography performed 2 weeks or more after the injury will assess the distribution and degree of injury. Fortunately, most cases of axonotmesis recover within 1 year (Clancy et al., 1977).

Cervical Cord Neurapraxia Cervical cord neurapraxia is characterized by an acute, transient sensory or motor change, or both, to more than one extremity. Symptoms include burning pain, numbness, and tingling with or without paresis or complete paralysis. Transient quadriplegia is a type of neurapraxia characterized by temporary paralysis and loss of motor function in all four limbs (Torg et al., 1986). Burning hands syndrome is characterized by burning dysesthesias of the hands and associated upper extremity weakness (Maroon, 1977). Episodes of cervical cord neurapraxia usually resolve within 10 to 15 minutes, although gradual resolution may take more than 24 to 48 hours. Congenital or degenerative narrowing of the anteroposterior (AP) diameter of the cervical spinal canal is an established risk factor for cervical cord neurapraxia (Torg et al., 1997). Athletes with an episode of cord neurapraxia should be held from competition and undergo radiographic evaluation and MRI. Return to play after an episode of cervical cord neurapraxia is a highly controversial area in sports medicine. Several cases of permanent neurologic injury following cervical cord neurapraxia associated with cervical spinal stenosis have been reported (Brigham and Adamson, 2003; Cantu, 1993, 2000). Functional spinal stenosis on advanced imaging in an athlete with a history of cervical cord neurapraxia is an absolute contraindication to return to play in contact and collision sports (Cantu, 2000).

Catastrophic Cervical Spine Injury Injury to the spinal cord resulting in temporary or permanent neurologic injury is a rare but potentially catastrophic event during sports competition. Cervical spine trauma is most common in contact and collision sports such as American football, rugby, ice hockey, gymnastics, skiing, wrestling, and diving (Cantu and Mueller, 1999; Carvell et al., 1983; Tator and Edmonds, 1984; Wu and Lewis, 1985). Cervical spinal cord injuries are the most common catastrophic injury in American football and the second leading cause of death attributable to football. The National Center for Catastrophic Sports Injury Research reported that the incidence of cervical spinal cord injury in American football between 1977 and 2001 was 0.52, 1.55, and 14 per 100,000 participants in high school, college, and professional football, respectively (Cantu and Mueller, 2003). Axial loading is the most common mechanism for catastrophic injury to the cervical spine during sports competition (Torg et al., 1979, 1990). Axial loading occurs when a player strikes another player with the top of the head as

the point of initial contact (“spear tackling”). In athletes with cervical spinal stenosis, axial loading followed by forced hyperextension or hyperflexion can further narrow the AP diameter of the spinal canal, resulting in compression of the spinal cord and transient or permanent neurologic changes (Eismont et al., 1984; Penning, 1962; Torg et al., 1993). Recognition of the axial load mechanism as the major cause of catastrophic cervical spine injury in American football resulted in rule changes that banned “spearing,” defined as intentionally striking an opponent with the crown of the helmet, as well as other tackling techniques in which the helmet is used as the initial point of contact. In 1976 the incidence of quadriplegia was 2.24 and 10.66 per 100,000 in high school and college athletes, respectively. In 1977, only 1 year after rule changes that banned spear tackling, the incidence decreased to 1.30 and 2.66 per 100,000 in high school and college athletes (Torg et al., 2002).

On-the-Field Assessment Medical providers at sporting events must be prepared to assess, stabilize, and transport athletes with suspected cervical spine injuries. Adequate preparation of and anticipation in required personnel and equipment and a well-designed emergency response are critical to the management of catastrophic neck injuries. In general, any athlete with significant neck or spine pain, diminished level of consciousness, or significant neurologic deficits should be immobilized and prepared for transport. Guidelines for the prehospital care of the spine-injured athlete were established by the Inter-Association Task Force for Appropriate Care of the Spine-Injured Athlete (2001). The initial assessment of an injured athlete begins with a basic assessment of the ABCs and level of consciousness. EMS personnel should be contacted for any concerns regarding basic life support. Unconscious athletes are presumed to have unstable spine injuries until proven otherwise. The face mask of a protective helmet should be removed as soon as possible, regardless of respiratory status (InterAssociation Task Force, 2001). In football the face mask can be removed with screwdrivers or the loop straps cut with various cutting tools such as pruning shears or a Trainer’s Angel (Knox and Kleiner, 1997). Football helmets and chin straps should be left in place. If the helmet is removed from a downed player wearing shoulder pads, the athlete’s head will hyperextend, which may result in secondary injury to the cervical spine. If the athlete is not breathing, an adequate airway can be established by the jaw thrust maneuver, which allows opening the airway while maintaining the cervical spine in a stable position. Rarely, assisted ventilation may be necessary. If transport is indicated, the athlete should be immobilized to a spine board. A supine athlete can be transferred to a spine board using a six-plus person lift technique, with one person responsible for stabilization of the head and neck (Inter-Association Task Force, 2001). To transfer an athlete who is facedown, a logrolling technique is recommended. Transport of a spine-injured athlete should be directed to a trauma center or medical facility with diagnostic and surgical capabilities for spinal injury. 585

29

Sports Medicine

KEY TREATMENT Athletes with an episode of cervical cord neurapraxia involving sensory or motor changes, or both, to more than one extremity should be held from competition and undergo radiographic evaluation and MRI to rule out functional spinal stenosis. In an athlete with a history of cervical cord neurapraxia, functional spinal stenosis on advanced imaging is an absolute contraindication to return to play in contact and collision sports (SOR: C; Cantu, 2000; Inter-Association Task Force, 2001).

Environmental Influences Exertional Heat Illness Key Points • H ydration sufficient to replace fluid lost in sweat is essential to prevent heat stroke. • Athletes exercising in the heat who exhibit mental status changes must be immediately removed from competition and cooled. • Ice-water immersion produces the most rapid decrease in core body temperature.

Heat stroke is the third leading cause of death in high school athletes (Lee-Chiong and Stitt, 1995). This is tragic because these deaths should be largely avoidable. The exercising human is an engine operating at about 25% efficiency, resulting in 3 W of heat production for every watt of work, and requires a biologic radiator to avoid overheating. Humans dissipate heat through convection, conduction, radiation, and evaporation, with evaporative sweat loss being the most significant. Higher temperatures limit heat dissipation from convection and conduction, warm sunny days elevate body temperature through radiant heating, and higher humidity decreases evaporative cooling. Thus, the combination of high ambient temperature, radiant heat from the sun, and high humidity works synergistically to create dangerous playing conditions that promote the development of heat illness. The wet bulb globe temperature (WBGT) index incorporates ambient temperature, relative humidity, and the amount of radiant heat coming from the sun to provide a measure of the risk of overheating. The American College of Sports Medicine Inter-Association Task Force on Exertional Heat Illnesses Consensus Statement (2006) recommends that WBGT readings from 18° to 23° C (64.4°-73.4° F) result in moderate risk, 23° to 28° C (73.4°-82.4° F) in high risk, and more than 28°C (82.4° F) in extreme risk. The cumulative effect of successive days of exercise in the heat must also be considered. In a U.S. Marine Corps, investigators demonstrated that the risk of exertional heat illness was best predicted by considering the current and the previous day’s WBGT index (Wallace et al., 2005). Because evaporative cooling is the primary mechanism for heat dissipation, adequate hydration is essential to keep the biologic radiator functioning. Losses of 2% to 3% of body weight are common with high-intensity exercise in the heat (Galloway, 1999). Below 5% fluid losses, performance and thermoregulation are impaired, and thirst is an inconsistent 586

stimulus to rehydrate, so regular, planned fluid consumption is essential. Fluid recommendations vary, but experts have suggested about 500 mL of fluid intake 2 hours or less before exercise and then about 250 mL every 20 minutes during exercise (Convertino et al., 1996). Because of differences in sweat rate, acclimatization, intensity of exercise, clothing, protective equipment, and environmental factors, individual fluid requirements vary. Thus, recording an athlete’s nude weight in the morning and evening is an effective method for determining adequate rehydration. If athletes are losing more than 2% to 3% of their body weight with training, they need to consume more fluids during training. If they cannot regain the lost weight before the next morning’s training, they need to consume additional fluids after training and during recovery time. For every kilogram of body weight lost, 1 L of fluid should be consumed. Cooler, flavored fluids are recommended to increase palatability and absorption. Heat illness is classified as heat edema, heat cramps, heat syncope, heat exhaustion, and heat stroke (Table 29-1) (Binkley et al., 2002; Eichner, 1998). Heat stroke is of the greatest concern, with hallmark features of an elevated core temperature higher than 40.5° C (105° F) and associated mental status changes. Any athlete exhibiting mental status changes and participating in an environment conducive to heat illness requires immediate removal from participation and active cooling. An ice-water tub should be prepared in advance if rapid cooling may be necessary in high-risk events, and an affected athlete should be fully submerged, with only the head above water (Smith, 2005). Other methods of cooling, such as applying ice bags to the neck, axilla, and groin, or using cold-water spray combined with fanning, can be effective, but the rate of core body temperature loss is slower than in ice-water immersion. Close monitoring of mental status and vital signs (e.g., core temperature) is indicated, and athletes should be transported to the hospital if they do not exhibit improving mental status with normalization of vital signs. The National Athletic Trainers’ Association Exertional Heat Illness Position Statement is an excellent reference regarding proper preparedness for heat illness (Binkley et al., 2002).

Exertional Hyponatremia Key Points • L ife-threatening hyponatremia develops when excessive hypotonic fluid is consumed, with concomitant sodium sweat loss. • Exertional hyponatremia most often occurs in women completing endurance races in over 4 hours who drink copiously throughout the race. • Symptoms of exertional hyponatremia include mental status changes and peripheral edema, without significant elevation in core temperature.

Exertional hyponatremia (serum sodium 100%), any tenting of the skin, significant comminution, or excessive shortening (>2 cm) may warrant surgical intervention, and referral to an orthopedist is recommended. Distal clavicle fractures have a higher rate of nonunion with nonsurgical treatment than midshaft or medial fracture patterns, so careful follow-up is necessary (Kahn et al., 2009; McKee et al., 2004). 603

30

Common Issues in Orthopedics

Acromioclavicular Joint Acromioclavicular (AC) joint injuries are classified by the ligamentous structures involved and the degree of separation of the AC joint (Fig. 30-3). A grade 1 injury involves only a partial injury to the AC ligaments, no displacement occurs, and the coracoclavicular (CC) ligaments are intact. A grade 2 injury involves the complete injury of the AC ligaments, and therefore mild superior translation of the distal clavicle occurs (100% displacement). Stress radiographic views may magnify this separation even further; however, stress views rarely alter the treatment plan and are painful to patients and thus no longer considered required diagnostic images. Treatment of grade 3 AC injuries is controversial and ranges from surgical to conservative treatment with a sling. With conservative treatment, the distal clavicle may ultimately heal in a superiorly translated position, leaving a prominent bump over the lateral aspect of the shoulder. However, nonelite athletes can function well and have a full return to activities. Acute repair of grade 3 injuries is suggested more for elite athletes, but has not been proved in randomized, controlled trials (RCTs) because subtle changes occur at this important point in the kinetic chain. Chronic reconstructions have been suggested in patients who have grade 3 injuries but with residual pain or dysfunction. The more severe injuries of the AC joint have significant posterior, superior, or inferior displacement and require surgical reduction and repair. A grade 4 AC separation is a complete injury of both AC and CC ligaments with a posterior subluxation of the distal clavicle relative to the acromion. These are frequently missed on routine anteroposterior (AP) radiographs but can be easily identified if routine axillary shoulder views are obtained. Fundamental management of bone and joint injuries requires a view from two perspectives. Grade 5 injuries are basically equivalent to severe grade 3 injuries where the distal clavicle is riding so high that it either buttonholes through the fascia or tents beneath the skin (300% translation). The fascial injury prevents reduction, and the pressure on the undersurface of the skin risks skin slough or an open injury. Finally, grade 6 AC injuries are extremely rare and are associated with an inferior dislocation of the distal clavicle beneath the coracoid.

Sternoclavicular Joint Patient with sternoclavicular (SC) injuries present with a history of trauma (e.g., landing on lateral aspect of shoulder) or a history of chronic overuse that has led to popping and pain over the medial aspect of the clavicle (Matave et al., 2005). Acute SC joint dislocations can be identified clinically with localized tenderness over the medial clavicular aspect, and gross deformity may be present. More often, however, patients present with a subtle chronic situation caused by esthetic findings with a palpable or gross asymmetry. The examination should always include an assessment of the patient’s airway and circulation, 604

including cervical venous distention, because the great vessels and trachea lie immediately posterior to the SC joints (Fig. 30-4). Imaging studies should include an AP radiograph of the chest, views of the entire clavicle, and a tangential or serendipity view of the SC joint (Fig. 30-5). Because of overlapping shadows, these studies may be difficult to interpret. When suspicious, the best test is computed tomography (CT). Traumatic SC joint dislocations can be either anterior or posterior. Anterior dislocations are generally easily palpated, with the proximal clavicle anteriorly displaced and painful. Anterior injuries may be reduced by placing a rolled towel or beanbag between the shoulder blades, then creating a distraction force along the arm in extension. Anterior dislocations tend to be unstable and to redisplace after attempted reduction. Fortunately, anterior injuries usually heal uneventfully, leaving an asymptomatic medial prominence and occasional popping, with minimal effect on the patient’s activities of daily living. Posterior dislocations can be dangerous because of proximity to the great vessels posteriorly. If patients have venous engorgement in the neck and difficulty breathing, closed reduction may be attempted. A towel clip is used at the medial end of the clavicle, pulling anteriorly and creating the reduction. If this is attempted, a vascular surgeon should be available in case the proximal clavicle was actually tamponading an injury to the great vessels. This reduction should never be performed on the sideline in the absence of immediate cardiothoracic surgical response, unless the patient’s life is at risk and there is no other option. When treating injuries to the proximal clavicle, age of the patient and normal maturation of the proximal epiphysis are also important considerations. The medial clavicle epiphysis is one of the last to appear, at 19 to 23 years of age, and then the last to fuse, at 23 to 25 years of age. In patients younger than 23, these injuries are generally physeal injuries and not true dislocations, reducing the need for aggressive treatment (Fig. 30-6).

KEY TREATMENT Subacromial injection for rotator cuff disease or intra-articular injection for adhesive capsulitis may be effective, although the effect may be minimal and not well maintained (Buchbinder et al., 2003) (SOR: A). The use of some physiotherapy interventions is indicated in specific and circumscribed cases of shoulder pain (Green et al., 2003) (SOR: B). Little evidence supports the benefit of manual therapy for adhesive capsulitis, shoulder pain, or subacromial impingement syndrome (Ho et al., 2009) (SOR: A). The use of acupuncture for shoulder pain can be neither recommended nor refuted (Green et al., 2005) (SOR: A).

Shoulder Impingement and Rotator Cuff Disease Key Points • T ests to diagnose impingement syndrome include a positive Hawkins test, a painful arc of motion, and weakness with external rotation. • Tests to diagnose a complete cuff tear include a positive drop-arm test, a painful arc of motion, and weakness to external rotation. • Incomplete tears of the rotator cuff improve with physical therapy, anti-inflammatory medications, or subacromial injection.


Grade 1

Grade 2

Grade 3

Grade 4

Conjoined tendon of biceps and coracobrachialis

Grade 6 Grade 5 Figure 30-3 Progressive severity of acromioclavicular (AC) joint injuries. Grade 1 indicates incomplete injury of ligaments. Grade 2 has complete injury of the AC ligaments but intact coracoclavicular (CC) ligaments. Grade 3 injuries have complete injury of both AC and CC ligaments. Grade 4, 5, and 6 injuries are progressively severe, with posterior displacement of clavicle, severe superior displacement of clavicle, and inferior displacement of clavicle beneath the coracoid process.

605

30


By far the two most common diagnostic categories about the shoulder are rotator cuff impingement and shoulder instability. The rotator cuff is a group of four muscles—supraspinatus, infraspinatus, teres minor, and subscapularis—that originate from the scapular surface, traverse just outside of the glenohumeral capsule, and insert onto the tuberosities of the humerus (Fig. 30-7). The rotator cuff initiates motion in the shoulder and stabilizes the humeral head in the glenohumeral joint. The diagnosis of rotator cuff impingement is actually a continuum of pathologies, including subacromial bursitis, AC joint hypertrophy and spurring, rotator cuff tendinosis, partial rotator cuff tears, complete or massive rotator cuff tears, and ultimately, rotator cuff arthropathy; that is, degenerative disease related to chronic rotator cuff insufficiency (Almekinders, 2001). Patients generally present with shoulder pain exacerbated by repetitive overhead activities, perhaps weakness, and occasionally difficulty sleeping on the shoulder. Physical examination of the shoulder includes provocative maneuvers that exacerbate impingement findings and evaluate the function of each rotator cuff muscle (Tennent et al., 2003a, 2003b). Impingement

Figure 30-4 Drawing shows proximity of major neurovascular structures to sternoclavicular joint.

testing includes straight, forward flexion of the shoulder (Neer sign), abduction and internal rotation of the shoulder (Hawkins sign), and adduction of the shoulder in a 90-degree, forward-flexed position (Figs. 30-8 and 30-9). The examiner must be cautious with the latter test because it may be positive with impingement but also with AC joint hypertrophy alone or with degenerative change of the AC joint. Isolated testing of the rotator cuff is performed in sequence. To isolate the supraspinatus muscle, the examiner should perform the “empty can” test. This is performed with the arm slightly forward-flexed in the plane of the scapula, abducted to 90 degrees, with full internal rotation (i.e., with thumbs down, or empty can). The examiner should then place resistance on the patient’s distal hand in an inferior direction. If this exacerbates pain, it is a positive finding of impingement or rotator cuff tendinopathy. If the patient has a positive “drop arm” sign, unable to maintain the arm in this position, a complete rotator cuff tear should be suspected. However, this does not confirm a complete rotator cuff tear because the patient may be guarding secondary to pain. Clinically, the examiner can clarify the difference by performing a diagnostic subacromial injection with lidocaine. The injection should significantly diminish pain complaints but not affect the motor function of an intact rotator cuff (Park et al., 2005). To evaluate the infraspinatus and teres minor muscles, the examiner should evaluate external rotation against resistance. This is best done with the arm at the side, keeping the elbows near the torso, and asking the patient to rotate externally against resistance. Isolating the subscapularis muscle is more difficult. Resisted internal rotation with the arms at the side will recruit the pectoralis muscles and not isolate the subscapularis. To isolate the subscapularis, two tests have been described. In the lift-off test, the patient places the arm behind the back and lifts the hand into further internal rotation against resistance (Fig. 30-10). If able to do this, the patient’s subscapularis muscle is likely intact. Modification of this test has been described as the “tummy pat” or the “Napoleon” test, in which the patient abducts the elbow, which must be away from the body in the plane of the torso, and is then asked to pat the stomach against resistance

40°

0"

–6

" 45

Figure 30-5 Technique in obtaining a tangential radiographic image, the serendipity view, to assess sternoclavicular joint injuries.

606


(Fig. 30-11). Weakness or inability to press against resistance is considered to be a positive test. Once the diagnosis is made clinically, AP and axillary shoulder x-ray studies can be obtained to evaluate the extent of injury further or assess for concomitant injuries. MRI is not routinely indicated with an intact rotator cuff clinically, and we usually recommend trying a course of physical therapy for 6 to 12 weeks before ordering MRI (Park et al., 2005). Epiphysis

Periosteum

Ligament intact to periosteum

A

New bone with remodeling of clavicle

B Figure 30-6 Medial clavicle injuries in patients younger than 23 to 25 years are likely physeal injuries and have the potential to remodel.

If the patient has intact rotator cuff function on clinical examination and otherwise normal findings on radiographs, a conservative course of physical therapy is indicated for the impingement symptoms. From 90% to 95% of patients with incomplete tears of the rotator cuff improve with the course of physical therapy, anti-inflammatory medications, or a subacromial injection, although some may require surgery eventually (Matava et al., 2005). Physical therapy should focus on rotator cuff strengthening, ROM, posterior capsular stretching, and scapular stabilization. If patients fail a 6- to 12-week course of conservative treatment, a corticosteroid injection should be considered before surgery. If a patient is refractory to both corticosteroids and physical therapy, surgical intervention may be indicated. This is a more appropriate time to order an MR image because preoperative MR scanning can evaluate the extent of rotator cuff pathology, associated spurring, and degeneration within the shoulder joint. Although not necessary for making the diagnosis, MRI can assist the surgeon at surgery. For incomplete rotator cuff tears (390 patients), no definitive evidence supports or refutes the efficacy of common interventions, including physiotherapy, NSAIDs, corticosteroid injections, or open and arthroscopic surgery, for rotator cuff tears in adults (Ejnisman et al., 2003) (SOR: A). • Based on limited data from two quality RCTs, no evidence supports the superiority of conservative versus surgical treatment for subacromial impingement syndrome (Dorrestijn et al., 2009) (SOR: B). • Review of 14 RCTs evaluating rotator cuff surgery showed no long-term pain benefit of surgical decompression versus exercise programs (Coghlan et al., 2009) (SOR: A).

Figure 30-10 Lift-off test is used to assess subscapularis muscle function. Patients are asked to lift their hand off their back against resistance. Weakness or pain indicates subscapularis pathology. (Courtesy Mark R. Hutchinson, MD.)

Figure 30-8 Hawkins test for shoulder impingement is performed by forward-elevating the humerus against the fixed scapula. Pain indicates anterior impingement. (Courtesy Mark R. Hutchinson, MD.)

Figure 30-11 “Napoleon” or “tummy pat” test is a modified lift-off test to evaluate subscapularis function. Patients are asked to maintain their elbow laterally while pressing into their belly. (Ensure that patients do not drop their arm and use their humerus extensors to mimic subscapularis function.) (Courtesy Mark R. Hutchinson, MD.)

Figure 30-9 Neer test for shoulder impingement is performed with abduction and internal rotation of the shoulder. Pain indicates lateral impingement. (Courtesy Mark R. Hutchinson, MD.)

Shoulder Instability Bony anatomy provides minimal stability to the glenohumeral joint; therefore the primary stability depends on both static and dynamic soft tissue structures. The static soft tissue structures include the fibrocartilaginous labrum, 608

g lenohumeral ligaments, and capsule. The labrum attaches to the periphery of the glenoid and serves to deepen the socket, reducing translation out of the socket. The glenohumeral ligaments attach to the labrum, are thickenings in the capsule, and connect to the humeral head. The intrinsic dynamic stabilizers are the rotator cuff and biceps, which help to maintain the humeral head in the glenoid socket. The extrinsic dynamic stabilizers include the rhomboid, levator scapulae, serratus, and trapezius muscles, which position the glenoid beneath the humeral head. The diagnosis of shoulder instability begins with the patient’s history and mechanism of injury, which often include episodes of subluxation, dislocation, or apprehension. Classically, anterior instability is appreciated when the arm is placed in abduction and external rotation (Tennent et al., 2003a, 2003b) (Fig. 30-12). Inferior instability is appreciated


Figure 30-12 Apprehension test is performed with the arm in full abduction and external rotation. Sensation of impending subluxation is a positive finding. ( Courtesy Mark R. Hutchinson, MD.)

when the patient tries to hold a heavy object and the shoulder subluxes inferiorly. Posterior instability is frequently associated with a fall on an outstretched arm, or occasionally with weightlifters who lock out their arms in extension while bench pressing. The clinical examination targets these specific pathologies with the classic apprehension test for anterior instability, performed with the arm in abduction and external rotation, and the patient having the sensation of the arm going out of place. In the relocation test the examiner then presses the humeral head back into a reduced position, thus eliminating the sensation of apprehension. Posterior instability is assessed in a supine position with the arm forward-flexed 90 degrees with a posteriorly directed force. Inferior instability is assessed by pulling inferiorly on the arm and looking for or feeling the humerus come out the socket and looking for a concavity just below the acromion, called the “sulcus sign” (Fig. 30-13). Some patients may have generalized ligamentous laxity, but laxity itself is not a painful process and is therefore not pathologic. However, some patients with generalized ligamentous laxity do have symptoms of instability and pathology that can be assessed by comparison to the opposite side or looking at the elbows, fingers/thumb, or knees for excessive recurvatum, In general, patients with generalized ligamentous laxity should undergo an extensive course of conservative treatment because of the increased risk of failure associated with most surgical interventions compared to simple unidirectional instability. The conservative treatment of shoulder instability is targeted at balancing the flexibility, optimizing the motor strength, and optimizing the function of the kinetic chain. The core component is rotator cuff–strengthening exercises as well as scapular stabilizer exercises. Controversy surrounds the ideal treatment for a first-time shoulder anterior dislocation. In young athletes or military populations, the risk of recurrence and future shoulder problems approaches 90%. Surgical treatment with repair of labral detachments has led to a high rate of return to play and return to performance, with a low risk (40) with first-time dislocation have a reduced risk of recurrent instability (3 mm) (“David Letterman” sign). Patient recovered with only splint support. (From Nicholas J, Hershman E. The Upper Extremity in Sports Medicine, 2nd ed. St Louis, Mosby, 1995, p 456.)

of the wrist at the scapholunate joint just distal to Lister’s tubercle (bump on distal radius) on the dorsal aspect of the wrist. Physical examination typically reveals no gross deformities, although dorsal swelling may be noted. The pain may be exacerbated by flexion and extension while palpating directly over the scapholunate joint on the dorsal aspect of the wrist. Impacts strong enough to cause scapholunate sprain are sufficient to cause fracture. Therefore, plain radiographs should be obtained in all patients with suspected scapholunate sprain to look for associated fracture or avulsion. The series should include a standard AP view, AP with a clenched fist (accentuates scapholunate joint widening), standard lateral view, and posteroanterior (PA) view in ulnar deviation (assess scaphoid bone better for fracture). It is often helpful to obtain a comparison AP view of the opposite wrist. An increased gap between the scaphoid and lunate bones of 2 to 3 mm on the AP projection (e.g., “Terry Thomas” [U.K.] or “David Letterman” [U.S.] sign, for their gapped-tooth grin) is indicative of scapholunate dissociation (Fig. 30-22). Patients with a “simple” scapholunate sprain require protection and rest with a period of splinting. This can be accomplished with a custom fiberglass or plaster splint, or a prefabricated cock-up wrist splint until the patient is asymptomatic. After initial treatment, the patient is weaned from the wrist splint and begins active ROM and hand-strengthening therapy. In patients with scapholunate dissociation, surgical consultation should be considered early, and referral to a hand specialist is encouraged. Fixation of the joint is often needed to maximize future wrist function (Fig. 30-23).

Distal Radius Fractures Patients with distal radius fractures most often present with wrist pain and deformity immediately after a fall. All patients with wrist pain after a fall should have AP, lateral,

Figure 30-23 Postoperative radiograph with scapholunate joint reduced and two K wires properly positioned to stabilize the joint. (From Nicholas J, Hershman E. The Upper Extremity in Sports Medicine, 2nd ed. St Louis, Mosby, 1995, p 393.)

and oblique radiographs of the wrist. Deformity may or may not be present, and some patients may complain of paresthesias in the affected extremity. A patient’s ability to move the wrist does not rule out fracture. It is important to palpate the entire extremity to assess any injury above or below the primary injury site for concomitant fractures. If suspected, radiograph those areas as well. Neurovascular status should always be evaluated and documented. 615

30


Treatment is based on fracture type, patient age, and demand. A nondisplaced or minimally displaced fracture can be initially treated in a splint for 5 to 7 days until swelling subsides, then casted in a short-arm cast. Average healing time is 4 to 8 weeks, and repeat radiographs should be obtained during the healing process at an interval of every 2 to 3 weeks. An extra-articular, angulated fracture is initially treated with closed reduction with block (lidocaine injection into fracture hematoma). If postreduction alignment is adequate, a splint can be placed for 5 to 7 days to maintain the alignment pending casting. Because displacement or angulation of fracture fragments is a high risk even when appropriately splinted or casted, radiographic follow-up is important, and distal radius fractures are often treated by an orthopedic surgeon. Comminuted or displaced intra-articular fractures usually require closed reduction with percutaneous pinning or open reduction, internal fixation to maintain position and articular surface integrity; orthopedic surgery referral is recommended.

Scaphoid Fracture Patients typically present after a fall onto an outstretched hand and complain of pain and swelling in the radial aspect of the wrist, worsened by motion. Gross deformity is not usually seen. The most common physical examination finding is tenderness with palpation over scaphoid tubercle or in the anatomic snuffbox. Radiographs should be obtained in all patients with suspected scaphoid injury, including AP, lateral, and oblique views, as well as PA ulnar deviation or scaphoid views (Fig. 30-24). Importantly, radiographs are often negative shortly after immediate injury and up to 14 days; radiographs should be repeated in 2 weeks if suspicion remains high. Because a fracture is suspected, interim splinting or casting is necessary. Other diagnostic tests may be obtained if repeat x-ray films are negative after 2 weeks and the patient is still symptomatic, or if definitive diagnosis is needed sooner than the planned 2-week follow-up. These tests may include radionuclide bone scan (usually positive within 2-3 days of injury), CT, or MRI. Treatment of scaphoid fracture is initiated if suspicion is high, even though radiographs are initially negative. If fracture is ruled out at follow-up visits, treatment is adjusted accordingly. Nondisplaced scaphoid fractures are treated with cast immobilization. Thumb spica casting is essential, but whether the initial cast needs to be a long-arm or shortarm variety is controversial. Studies have shown decreased time to union and reduced rates of delayed union and nonunion with a long-arm thumb spica cast (Gellman et al., 1989). However, union rates of up to 95% with short-arm casting have been reported. A combination, with a long-arm cast for the initial 6 weeks followed by short-arm casting from 6 weeks until radiographic healing is present, addresses both these key issues. Healing rates and average healing time depend on location of the fracture because the blood supply differs throughout the scaphoid. Nondisplaced distal pole fractures tend to receive a better blood supply and have a healing rate of close to 100%, with average healing time of 10 to 12 weeks. Scaphoid waist fractures have a healing rate of 80% to 90%, with average healing also 10 to 12 weeks. Proximal pole fractures have a healing rate of only 60% to 70%, with average healing time of 12 to 20 weeks. Poor outcomes (i.e., nonunion, 616

malunion) in any scaphoid fracture are more likely to occur if the diagnosis or appropriate treatment is delayed; this is why it is important to initiate treatment based on suspicion of injury with normal radiographs. Fractures that are displaced (≥1 mm) can be treated with closed immobilization, but the risk of poor outcome is high. These fractures should be referred to an orthopedic surgeon for consideration of surgical fixation.

EVIDENCE-BASED SUMMARY • O ne controlled study showed significant benefit of steroid injections for DeQuervain’s tenosynovitis. Because of a limited number of patients and limited quality supportive studies, however, definitive recommendations cannot be made (Peters-Veluthamaningal et al., 2009a) (SOR: B). • Pain and symptoms of people with “trigger finger” may improve with a corticosteroid injection (Peters-Veluthamaningal et al., 2009b) (SOR: A). • Bone scintigraphy and MRI have equally high sensitivity and high diagnostic value for excluding scaphoid fracture. However, MRI is more specific and better for confirming scaphoid fracture (Yin et al., 2009) (SOR: A). We believe additional studies are needed to assess diagnostic performance of CT.

Knee Key Points • In clinical examination of ligament injuries about the knee, the Lachman test is the most sensitive for anterior cruciate ligament (ACL) instability. • The clinician should maintain a high level of suspicion of associated ligament injuries, especially the lateral collateral ligament (LCL) and posterolateral corner. Acute surgical intervention (within 3 weeks) of LCL and posterolateral corner injuries significantly improves prognosis. • Viscosupplementation, therapeutic exercise, and oral supplementation with glucosamine and chondroitin sulfate may all provide some symptomatic relief and functional improvement for generalized knee arthritis. Arthroscopic debridement alone (in the absence of loose bodies, cartilage flaps, and meniscus tears) may not provide relief. • Vertical, peripheral meniscus tears in the vascular zone of the meniscus of young patients should be treated with meniscus repair whenever possible to avoid focal increased pressures in the articular surface and future risk of degenerative joint disease. • In older patients with degenerative meniscus pathology and no locking, prevention of arthritic progression may be surgical or nonsurgical. When performed, partial is preferred to complete meniscectomy.

Degenerative Osteoarthritis Degenerative osteoarthritis (OA) of the knee is caused by loss of the hyaline cartilage along the knee joint surfaces. This can occur in an isolated compartment or diffusely throughout all three compartments of the knee. OA more often develops in the medial side or medial compartment of the knee, first


A

B

C

D

Figure 30-24 24 Transverse fracture through waist of scaphoid. (Courtesy James L. Moeller, MD.)

treatment for knee arthritis should include a generalized conditioning program, weight loss, a knee sleeve to improve the proprioceptive control, cushioned shoes, and NSAIDs. Oral supplementation with glucosamine and chondroitin sulfate may also be considered. If these do not provide relief after 4 to 6 weeks, corticosteroid or viscosupplement injections can be administered, typically with variable pain relief and duration. Injections may be repeated depending on patient response. In resistant cases, total or partial knee replacement can provide excellent pain relief and improve function. The effect of arthroscopy in patients with degenerative arthritis remains controversial (Hunt et al., 2002; Mosely et al., 2002). However, arthroscopy in the absence of loose bodies, cartilage flaps, or meniscal pathology is unlikely to be unsuccessful. Figure 30-25 Weight-bearing knee radiographs showing osteoarthritis.

leading to joint space narrowing and varus or bowleg deformity. Loss of articular cartilage and joint space on the lateral aspect of the knee leads to valgus or knock-knee deformity. Weight-bearing (standing flexed-knee PA) radiographs are strongly recommended to evaluate joint space narrowing and OA extent. Lateral and patella sunrise tangential views complete the study (Fig. 30-25). MR images are not routinely required and should not be ordered instead of plain x-ray films. MRI is best reserved for mechanical pathology or preoperative planning. X-ray findings include loss of the joint space, presence of osteophytes, subchondral sclerosis, and cysts. Patients with OA typically complain of knee pain and stiffness with walking, after prolonged sitting, descending stairs, and early in the morning. Swelling of knees and worse symptoms are typical with weather changes. Physical exam findings often reveal decreased ROM (flexion contractures), knee varus or valgus deformity, joint line tenderness, and crepitus with palpation during ROM. Treatment of OA is based on the patient’s age, demand, comorbidities, and severity of osteoarthritis. Conservative

EVIDENCE-BASED SUMMARY • T he short-term benefit of intra-articular corticosteroid in treatment of knee osteoarthritis is well established; however, longer-term benefits have not been confirmed, and the response to hyaluronic products appears to have more durability (Bellamy et al., 2005a) (SOR: A). • Based on a single RCT, bracing for OA may provide additional benefit compared to medical treatment alone (Brouwer et al., 2001) (SOR: B). • Land-based therapeutic exercise programs reduce pain and improve physical function for patients with OA of the knee (Brosseau et al., 2003; Fransen et al., 2001) (SOR: A). • Viscosupplementation (injection of hyaluronate) is an effective treatment for OA of the knee, with beneficial effects on pain and function (Bellamy et al., 2005b) (SOR: A). • Nonglucosamine preparations failed to show benefit, whereas glucosamine preparations were superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA (Towhead et al., 2009) (SOR: A). • Arthroscopic debridement has no benefit for undiscriminated OA with mechanical or inflammatory causes (Laupattarakasem et al., 2009) (SOR: A). • In OA patients, exercise results in a modest reduction in pain and a modest improvement in physical function (Fransen and McConnell, 2009) (SOR: B).

617

30


Infections Intra-articular joint infections are orthopedic emergencies and require urgent surgical irrigation and debridement as well as long-term antibiotic therapy. The most common source of infection is Staphylococcus aureus, which aggressively and quickly destroys cartilage and leaves the patient with permanent OA. Patients with a knee joint infection present with increased pain, swelling, warmth, redness, fever, and decreased ability to ambulate on that leg. Most patients will not want to move their knee at all. The knee should be aspirated and the fluid inspected and sent for laboratory analysis (Gram stain, cell count, culture, crystal evaluation). Crystalline arthropathy such as gout should always be considered because the aspirated fluid often appears cloudy and may mimic a joint infection. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) should also be obtained. Appropriate antibiotic treatment is initiated based on the offending organism. Although proposed in the medical literature for low-virulent organisms, serial aspiration is discouraged in the orthopedic literature, with surgical irrigation the preferred treatment.

Inflammatory Conditions Bursae are synovial fluid–filled structures or “cushions” that pad bony prominences as protection against repetitive impact from external forces or snapping anatomic structures, such as ligaments or tendons. Several bursae around the knee can become inflamed, irritated, and rarely, infected, including the prepatellar bursa, infrapatellar bursa, pes anserine bursa, and iliotibial (IT) band bursa (beneath IT band laterally). Knowing their anatomic location is important so that these bursae can be palpated directly (Fig. 30-26). Treatment of bursitis includes compression, ice, protective padding, and avoidance of impact on the bursa. NSAIDs may help to reduce swelling. If the fluid collection is large or an infection is suspected, aspiration of the bursa can be performed in the office with a large-bore needle under sterile conditions. The bursa fluid should be clear and straw colored or may be bloody in a traumatic injury. If an infection is not suspected clinically once the fluid is withdrawn, a corticosteroid can be injected. Corticosteroids should never be injected if infection is a possibility. Oral antibiotics can be started if an infection is present. Local I&D may be required with infection and abscess. Aspiration does not replace compression wrap, ice, and avoidance of impact. Reaccumulation of fluid may occur, but total volume usually decreases. Serial aspirations are an option in patients with recurrent aseptic bursitis.

Extensor Mechanism Problems The extensor mechanism comprises the quadriceps muscle, quadriceps tendon, patella, and patellar tendon. Differential diagnosis of problems in the extensor mechanism is broad, including muscle or tendon rupture, patellar fracture, patellar tendinopathy, patellofemoral syndrome, patellar instability, Osgood-Schlatter’s disease, and symptomatic medial plica. Examination of patients with anterior knee pain or extensor mechanism problems should always include a careful evaluation of the lumbar spine and hip to rule out 618

referred pain, as well as assessment of the antagonist hamstring muscles posteriorly. Hamstring tightness can exacerbate problems of tendinosis, patellofemoral syndrome, and instability. If the patient presents with focal tenderness over the patellar tendon at the distal pole of the patella, or potentially at the quadriceps insertion onto the patella, the likely diagnosis is tendinosis. Numerous studies show that chronic repetitive overuse does not actually lead to inflammation of the tendon itself, but rather to a central degeneration or tendinosis of the fibers of the tendon (Fithian, 2002). Steroid injections into patellar tendinosis are highly discouraged because they may predispose the tendon to complete failure. Treatment protocols for patellar tendinosis, or “jumper’s knee,” should include hamstring stretching, quadriceps strengthening with eccentric loading, and occasionally the use of a counterforce brace such as a Cho-Pat strap (Fig. 30-27). Alternative treatments, including deep friction massage, prolotherapy, platelet-rich plasma injections, topical antiinflammatory drugs, ultrasonic waves, and radiofrequency (RF) probes, show mixed results. Although no RCTs have yet proved their efficacy, these modalities have had some success. Surgical intervention for debridement of the tendinosis is uncommon but may be necessary to provide longterm relief. In the skeletally immature patient, tenderness at the distal pole of the patella may represent an avulsion apophysitis called Sinding-Larsen-Johansson disease. If the skeletally immature patient has pain at the insertion of the patellar tendon on the tibia, the most likely diagnosis is an apophysitis of the tibial tubercle, or Osgood-Schlatter’s disease. Both problems are more common during active phases of growth and are generally treated conservatively with rest, flexibility exercises, and gradual return to activity. Complete failure or rupture of the extensor mechanism at the patellar or quadriceps tendon requires surgical repair (Ilan et al., 2002).

Patellofemoral Syndrome Anterior knee pain has been variously termed patellofemoral syndrome and chondromalacia patellae. When treating anterior knee pain, the physician should identify the specific pathology to initiate targeted treatment. Chondromalacia patellae, or degenerative changes on the undersurface of the patella, is more common in young females. Pain complaints related to chondromalacia are exacerbated by sitting for an extended period with a flexed knee, doing deep squats, or going up and down stairs. Each of these activities increases the posteriorly directly forces of the patella, directing increased pressure onto the chondral surfaces. Treatment of these early arthritic changes is typically rehabilitation. Surgical intervention, such as cartilage scraping and debridement, has not been shown to provide long-term relief or benefit. In rare patients who have associated tight lateral retinacular structures and patellar tilt, surgical release of the lateral retinaculum can provide benefit. Conservative treatment of patellofemoral syndrome includes cushioned shoes, rehabilitation focused on the vastus medialis obliquus muscle, reductive taping techniques, hamstring stretches, and NSAIDs. Correction of the foot alignment with orthotic devices is also a treatment option, but supportive evidence is limited. From


Trochlear groove

Lateral epicondyle Lateral femoral condyle Intercondylar notch Iliotibial tract Gerdy’s tubercle

Adductor magnus

Adductor tubercle Medial epicondyle Medial femoral condyle Intercondylar eminence Anterior Patellar cruciate tendon ligament Tibial Sartorius tubercle Gracilis Patellar tendon Semitendinosus

Gastrocnemius, medial head

Deep medial ligament

Semimembranosus

Superficial medial ligament

B

A

Adductor magnus Plantaris Gastrocnemius, lateral head Fibular collateral ligament

Gastrocnemius, medial head

Gastrocnemius, lateral head

Fibular collateral ligament Anterior cruciate ligament Posterior cruciate ligament

Popliteus

Fibular collateral ligament Biceps femoris

Plantaris

Iliotibial band Patellar tendon Semimembranosus Popliteus

Soleus

C

D Figure 30-26 Line drawing shows anatomic sites of bursae around the knee.

70% to 80% of patients will improve with this conservative treatment. Unfortunately, the remaining patients with resistant symptoms can have a frustrating long-term therapeutic course, with guarded prognosis for any surgical intervention. Ultrasound therapy had no clinically important effect on patients with patellofemoral pain syndrome (Brosseau et al., 2001).

Meniscus Injuries The menisci are fibrocartilaginous structures situated on the tibial plateau both medially and laterally that help disperse the weight-bearing contact forces across the knee joint cartilage surfaces (Fig. 30-28). In the presence of a meniscus tear or the complete absence of a meniscus, focal stresses 619

30

Common Issues in Orthopedics Posterior cruciate ligament Ligament of Wrisberg Ligament of Humphry Medial meniscus

Popliteal tendon Fibular collateral ligament

Deep medial collateral ligament

Popliteal hiatus (recess)

Superficial medial collateral ligament

Lateral meniscus

A

Coronary ligament Capsule (meniscotibial)

Transverse ligament

Anterior cruciate ligament

F Figure 30-27 Counterforce brace (Cho-Pat strap) can be effective in reducing symptoms of patellar tendinosis (jumper’s knee).

increase. This in turn increases the loading of the hyaline cartilage and early progressive degenerative arthritis (Sherman, 1996). Meniscus tears can occur with axial loading but primarily occur because of twisting, cutting, or rotational forces. In older patients, meniscus tears may simply be a progression of the normal degenerative process. On physical examination, patients have pain over the medial or lateral joint line and may complain of snapping, popping, or catching within the knee (Greis et al., 2002a, 2002b). Varus or valgus loading may exacerbate pain as the meniscus is squeezed between the bony structures. Recurrent effusions may also represent intra-articular pathology. The most common test for meniscus injury is McMurray’s test (Fig. 30-29). The knee is hyperflexed, stressed with varus or valgus load, as well as internally and externally rotated, as the knee is brought into full extension. More simply, the examiner uses the lower leg and tibia to try to trap the torn meniscus between the tibia and the femur through a full knee ROM. If the examiner feels a snapping or a pop along the joint-line and the patient simultaneously complains of pain, the test is considered positive and highly indicative of a meniscus tear. A single finding may raise suspicion of a tear but does not confirm its presence. Indeed, sensitivity of both findings, the pop and pain, is over 90%. MRI can be used to confirm the diagnosis or assist preoperative planning but should never replace a thorough physical examination. Definitive treatment of meniscus pathology depends on the actual damage and pattern of the meniscus injury on MRI (Sherman, 1996; Greis et al., 2002a, 2002b) (Fig. 30-30). Depending on the pattern, the meniscus can either be reparable or nonreparable. Because of its essential role in sharing load and preventing the progression of degenerative arthritis, salvageable meniscus tears should always be repaired if possible. After debridement, patients can bear weight as 620

PCP M

T

B Figure 30-28 Medial and lateral meniscus anatomy as viewed from above (A) and via cross section (B). Note the circulation provided to the peripheral third of the meniscus only.

tolerated and usually return to full activities by about 3 or 4 weeks. With meniscus repair, recovery is extended and requires restricted weight bearing for 3 to 6 weeks, with 2 to 3 months needed before return to unrestricted activities.

EVIDENCE-BASED SUMMARY • W ith no RCTs, no conclusions about surgical or nonsurgical treatment of meniscal injuries can be drawn, or about meniscal tear repair versus excision. Partial meniscectomy seems preferable to total removal and improves overall recovery in the short term (Howell and Handoll, 2005) (SOR: B). • In a meta-analysis, sensitivity and specificity were 70% and 71% for McMurray’s test, 60% and 70% for Apley’s test, and 63% and 77% for joint line tenderness; no single test appears to diagnose a torn tibial meniscus accurately (Hegedus et al., 2007) (SOR: A).


Medial Collateral Ligament

A

The MCL is the most frequently injured ligament of the knee and often associated with concomitant ligamentous injuries; 95% are associated ACL ruptures. The MCL is the primary knee restraint to valgus loads. The MCL is tested in isolation at 30 degrees of knee flexion with a valgus load (Fig. 30-31); at 0 degrees, bony constraints contribute to stability. Valgus laxity at near or full extension implies concurrent injury to the posteromedial capsule and/or cruciate ligaments. Grade 1 injuries have pathologic laxity, indicated by increased medial joint space widening, of 1 to 4 mm; grade 2, laxity of 5 to 9 mm; and grade 3, more than 10 mm of increased laxity compared to the contralateral side. Imaging studies should include AP and lateral radiographs looking for associated bone injury or avulsions. MR scans may be of benefit in more severe injuries to look for additional associated soft tissue injuries. Initial treatment is nonsurgical for grade 1, 2, and 3 ligament sprains. Protected weight bearing is allowed with crutches and a hinged knee brace until pain resolves medially. Unrestricted ROM is allowed and encouraged. Most patients with MCL injuries do well with conservative treatment. Occasionally, patients with grade 3 injuries who do not respond to nonoperative treatment may require surgery. Timing of return to sport or function is related to severity of injury: grade 1 injuries, usually 1 week; grade 2, 2 to 4 weeks; and grade 3, 4 to 8 weeks.

Lateral Collateral Ligament and Posterolateral Ligament Complex

B Figure 30-29 Classic examination for meniscal pathology. A, Medial McMurray’s test is performed by palpating along the medial joint line (thin arrow) while creating a varus force (solid triangle), ranging the knee through flexion and extension, and internally and externally rotating the leg (yellow arrows). A positive finding is noted when the maneuver recreates the symptoms and the examiner feels a palpable click. B, Lateral McMurray’s test is done in a similar manner with valgus stress. (Courtesy Mark R. Hutchinson, MD.)

Ligamentous Injuries Four major ligaments keep the knee stable: anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL). They can be injured in isolation or in combinations related to knee dislocations. Most ligament injuries about the knee are not urgent. However, the primary care physician must remember (1) always to look out for the potential of a multiligament knee injury and the possibility of an arterial injury and (2) always to assess the LCL, based on the significantly poorer prognosis if the diagnosis and treatment are delayed beyond 4 to 6 weeks. Early identification and surgical repair of acute LCL injuries improve patient outcomes from 50% to 90%.

When evaluating the lateral side of the knee, the physician should evaluate the function of the LCL but also the stability of the knee to posterolateral rotation. The LCL is assessed with the knee unlocked at about 20 to 30 degrees of flexion with varus stress (Fig. 30-32). The posterolateral corner is tested by externally rotating the tibia when the knee is flexed at 30 and 90 degrees. If an increased spinout to external rotation is visualized compared with the opposite knee at 30 and 90 degrees, the patient has a posterolateral corner and PCL injury. If the knee spins out only at 30 degrees compared with the opposite side, an isolated posterolateral corner injury is present (Fig. 30-33). Imaging usually includes AP/lateral radiographs and MR image. Perhaps the simplest rule for primary care physicians is that any patient with acute varus instability (injury of LCL) should be referred to an orthopedic surgeon as soon as possible. Treatment is based on the severity of the injury. Nonsurgical treatment with protected weight bearing and protected ROM early for a few weeks is recommended for isolated grade 1 or 2 LCL; grade 1 is an opening of the lateral joint line less than 5 mm, and grade 2 is an opening of 6 to 10 mm. Progressive ROM and functional rehabilitation are initiated. Return to sports can be expected in 6 to 8 weeks. Surgical indications are recommended for isolated grade 3 LCL injuries (>10 mm gapping) and any rotator instability of the posterolateral corner. Acute surgery has more favorable outcomes, and early referral to an orthopedic surgeon is recommended. 621

30

Common Issues in Orthopedics Degenerative pattern

Degenerative flap

Traumatic pattern

Horizontal cleavage

Peripheral tear

Horizontal cleavage

Radial tear

Posterior horn

Anterior horn Complex

Figure 30-30 Representations of meniscus pathology. Degenerative tears tend to be complex, fibrinous, and horizontal. Acute tears that are vertical in the periphery may be reparable.

Figure 30-31 Valgus stress is used to assess function of the medial collateral ligament. To best isolate the MCL, the knee is unlocked to 30 degrees of flexion when stress is applied. If the knee is still unstable in full extension, other structures (PCL, ACL, posterior capsule) have been injured.

Figure 30-32 Varus stress is used to assess function of the lateral collateral ligament. Varus laxity noted in an acute knee injury should always be referred to an orthopedic surgeon; urgent primary repair of injured structures has a better prognosis than delayed reconstruction.

(Courtesy Mark R. Hutchinson, MD.)

(Courtesy Mark R. Hutchinson, MD.)

Posterior Cruciate Ligament The PCL is the primary restraint to posterior tibial translation in the knee. The most sensitive test for the PCL is the posterior drawer, which is a posterior-directed force on the knee with the knee flexed to about 90 degrees (Fig. 30-34). The PCL is usually injured secondary to a posteriorly directed force on the tibia, from a fall or potentially from a dashboard injury during a motor vehicle crash. Grading of the PCL 622

injury is based on the posterior drawer test and the relationship of the proximal tibia to the femoral condyles. In grade I PCL injuries, the tibial plateau is slightly anterior to the femoral condyles; in grade II, plateau and condyles sit flush at the same level; and in grade III the tibia is posterior to the level. Treatment of a PCL injury is guided by injury severity and associated ligamentous injuries (Cosgarea and Jay, 2001; Wind et al., 2004). Typically, grades I, II, and III are treated nonsurgically with bracing and functional rehabilitation, to


A

Figure 30-34 Posterior drawer is the most sensitive test for evaluating posterior cruciate ligament function. Place thumbs on femoral condyles, feeling the tibial offset at the level of the joint line (black arrow). Then create a posteriorly directed force (white arrows) and reassess the tibial step-off. (Courtesy Mark R. Hutchinson, MD.)

B Figure 30-33 Dial test is used to assess the posterior cruciate ligament (PCL) and posterolateral corner and is best done with patient prone and knees together. A, Normal examination should reveal symmetry with forced external rotation. B, If increased external rotation is identified with knee flexed 30 degrees, an injury to the posterolateral corner is identified. If asymmetry persists as knee is flexed to 90 degrees, the PCL is likely also involved. (Courtesy Mark R. Hutchinson, MD.)

focus on quadriceps strengthening. PCL ruptures, unlike ACL ruptures, tend to heal, and often a grade III will heal as a grade II, and a grade II as a grade I, with appropriate bracing and protection. Mild PCL laxity is usually not symptomatic for patients. If the knee becomes unstable, however, reconstruction can be delayed.

Anterior Cruciate Ligament The ACL is perhaps the most famous of knee ligaments because of its notoriety in twisting and cutting sports. The common presentation of an ACL injury is an athlete landing in a twisting and cutting sport, feeling a pop, and having an acute hemarthrosis within 24 hours. The most sensitive test

Figure 30-35 Lachman test is the most sensitive approach to assess anterior cruciate ligament function. The femur is stabilized (white arrows) with the knee flexed about 15 to 20 degrees and the tibia drawn anteriorly (yellow arrow). Comparison to the opposite side and assessment of a ropelike end point are key.

for ACL rupture is a Lachman test, which is basically an anterior translation of the tibia on the femur with the knee flexed 20 to 30 degrees (Fig. 30-35). The anterior drawer test is also used but is less sensitive (Fig. 30-36). The most specific test is the “pivot shift.” Initial treatment of ACL injury focuses on rehabilitation to regain ROM and strengthen the knee. Surgical indications are based on patient’s function as well as future demands (Beynnon et al., 2005). For young athletes who want to play a twisting or cutting sport more than two or three times per week, ACL reconstruction is strongly recommended. The key reason for that indication is the absolute requirement to avoid the current instability or pivoting. Recurrent wobbling or pivoting of the knee leads to an increase in stress along the meniscus, meniscal failure, meniscal degeneration, hyaline cartilage degeneration, and degenerative changes in 623

30


• E arly mobilization with external supportive device usually leads to a quicker recovery from ankle sprain, although it may not affect the long-term outcome. • Surgical repair of Achilles tendon tears leads to a reduced risk of rerupture, although surgical complications exist. • Although corticosteroid injections can provide short-term relief of plantar fasciitis pain, no single intervention appears superior to another. • Fractures through the watershed area of blood supply in the proximal fifth metatarsal (Jones’ fracture) has a high risk of nonunion/malunion and is often best treated surgically.

Figure 30-36 Anterior drawer test is less sensitive for isolating anterior cruciate ligament injuries but may assist in diagnosing associated pathology. The knee is flexed 90 degrees and the tibia drawn anteriorly. (Courtesy of Mark R. Hutchinson, MD.)

the knee. If the athlete is willing to give up his sport, with no complaints of instability performing activities of daily living, surgical ACL reconstruction is not always necessary. Skeletally immature athletes pose a unique challenge because of their open growth plates. Treatment options include delay of definitive surgical reconstruction until maturity, extra-articular reconstruction, and reconstruction with soft tissue across the physis (Bates et al., 2004). Most studies have shown that children are not fully cooperative with programs that have them reduce activities until skeletal maturity. This leads to recurrent episodes of instability with associated meniscal and cartilage damage. Based on this there has been a strong trend to surgically stabilize these young athletes to reduce the risk of arthrosis at a young age.

EVIDENCE-BASED SUMMARY • N o RCTs have compared surgical and nonsurgical outcomes in reduction of future osteoarthritic change for PCL injuries (Peccin et al., 1995) (SOR: A). • Based on two clinical trials in the 1980s and insufficient RCTs, no conclusions can be drawn about conservative versus surgical treatment of ACL ruptures in adults (Linko et al., 2005). • Surgical stabilization should be considered for skeletally immature patients with ACL injuries because they carry a high risk of recurrent instability and subsequent injury and damage to the meniscus (Bates et al., 2004) (SOR: B).

Ankle and Foot Key Points • R adiographs for foot and ankle imaging should be weight bearing if a fracture does not preclude it. • Radiographs are not necessary in all cases of suspected ankle sprain.

624

The foot and ankle are complex structures that provide the foundation to the musculoskeletal system and are intimately related to a person’s ability to ambulate, run, jump, and traverse unstable and variable terrain. Optimal foot and ankle function implies a higher level of function for activities of daily living. Thorough examination and imaging should consider a broad differential diagnosis of common problems, ranging from ligament sprains, stress fractures, fractures and avulsions, chronic tendinopathies, and tendon ruptures. A more expansive differential diagnosis includes nerve entrapment, circulatory dysfunction, and systemic disease, as well as congenital and developmental problems. All x-ray imaging of the foot and ankle for pain should be weight-bearing views in the absence of suspicion of a fracture, to allow a more accurate clinical picture because the patient usually experiences pain when weight bearing and not at rest (Stiell et al, 1992, 1993).

Ankle Sprains Sprains are injuries to the ligamentous structures of the ankle. About 85% of ankle sprains involve the lateral ligaments; medial and syndesmosis sprains make up the remaining 15%. Diagnosis is based primarily on history and physical examination, although radiographs are often helpful. Advanced diagnostic testing is not usually necessary. The family physician must be aware of the many potential pitfalls in the diagnosis of ankle sprain as well.

Lateral Ankle Sprains The anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL) are the three ligaments of the lateral ankle (Fig. 30-37). The ATFL primarily restricts anterior motion of the talus within the ankle mortise; the CFL restricts inversion; and the PTFL restricts posterior translation. The most common mechanism of lateral ankle sprain is an inversion ankle injury. Inversion events with the ankle in a plantar-flexed position often lead to ATFL injury (Fig. 30-38), whereas inversion events with the ankle in a dorsiflexed position more often lead to CFL injury (Fig. 30-39). Patients present due to ankle pain that may be associated with swelling, bruising, decreased motion, and increased pain with weight bearing, if able. Examination begins with observing the patient’s gait; a limp is often noted. Gross observation of the foot and ankle often reveals lateral edema and ecchymosis. Active motion may be severely restricted. Neurovascular structures are usually normal. Along with palpation of the ATFL, CFL, and PTFL, important structures to palpate on the lateral aspect


Posterior tibiofibular ligament

Calcaneofibular ligament

Anterior tibiofibular ligament Anterior talofibular ligament

Lateral talocalcaneal ligament Figure 30-37 Anatomy of lateral ankle ligaments. (From Nicholas J, Hershman E. The Lower Extremity and Spine in Sports Medicine, vol 1, 2nd ed. St Louis, Mosby, 1995, p 424.)

Figure 30-38 Forceful inversion of the hindfoot with a plantar-flexed ankle, possibly tearing the anterior talofibular and interosseous talocalcaneal ligaments. (From Meyer JM, Garcia J, Hoffmeyer P, et al. The subtalar sprain: a roentgenographic study. Clin Orthop 1988;226:169-173.)

of the ankle include the fibula (entire length), peroneal tendons, lateral process of the talus, neck of the talus, cuboid, and base of the fifth metatarsal. Stress testing is performed to assess the integrity of ligamentous structures. The anterior drawer test translates the talus within the mortise and assesses the ATFL, performed with the ankle in slight plantar flexion to place the ATFL under tension while decreasing CFL tension. Both the amount of excursion compared to the opposite side and the end-point feel to the test are important determinants in the evaluation. The CFL is tested by the talar tilt. The ankle is placed in a neutral position, putting tension on the CFL and decreasing tension on the ATFL. The talus is then inverted within the mortise while the examiner assesses excursion and end-point feel. Once again, these findings are compared to the opposite side to determine severity of injury.

Figure 30-39 Forceful inversion of the hindfoot with a dorsiflexed ankle, possibly tearing the calcaneofibular, cervical, and interosseous talocalcaneal ligaments. (From Meyer JM, Garcia J, Hoffmeyer P, et al. The subtalar sprain: a roentgenographic study. Clin Orthop 1988;226:169-173.)

In the United States, patients presenting for ankle injury often undergo radiographic evaluation, but the utility of routine radiographs to evaluate ankle injury is under debate. Well-designed studies from Canada have shown that many patients with ankle injury can be managed safely without routine radiographs. Indications for lateral ankle radiograph include age under 18 or over 55; inability to bear weight for four consecutive steps, either immediately after injury or in the examination room; and pain over the posterior portion of the distal 6 cm or at the tip of the fibula (Stiell et al., 1992, 1993). If pain is noted in the proximal or midshaft fibula, tibia/fibula films should be obtained, and pain over the base of the fifth metatarsal indicates the need for foot radiographs. Various scales are available to grade ankle injuries, and interexaminer variability is high. The most common scale is mild (grade 1), moderate (grade 2), and severe (grade 3). However, grading does not significantly affect treatment, complication rates, or long-term outcomes. Grading may have a predictive role in duration of recovery. Treatment of lateral ankle sprains has changed drastically over the past 25 years. Complete immobilization and rest were once thought to be important initial components of treatment. Currently, early mobilization with an external support device and rehabilitation are common therapies. Early immobilization may lead to greater stability and patient compliance, and the risk for early reinjury is low. In the early mobilization and rehabilitation plan, recovery tends to occur slightly quicker (based on full return to work), and early discomfort may be decreased (Eiff et al., 1994; Karlsson et al., 1996). With immobilization, the ankle joint can become stiff and lead to muscle atrophy. This may require a prolonged postimmobilization program focused on regaining motion and strength. Long-term outcomes of early mobilization and immobilization treatment plans are not significantly different. Basic stages of treatment include early external support and, depending on severity, limited weight bearing, pain control, reducing swelling with ice and elevation, and maintaining motion. Once the initial acute injury subsides, weaning from supportive devices such as crutches, walking boots or casts 625

30


should be done and formal rehabilitation initiated. Rehabilitation should focus on motion, strength, and proprioception activities. The final phase of rehabilitation is reintroduction of sport-specific tasks and return to sport. Participation in a prevention training program with a focus on balance and proprioception reduces the incidence of ankle sprain without increasing the incidence of other injuries (Bahr et al., 1997). Bracing the ankle on return to sport may reduce the risk of recurrent injury. Whether bracing reduces the risk of an initial sprain is under debate (Sitler et al., 1994; Surve et al., 1994). When treating skeletally immature patients, it is important to remember that physeal plate fractures through the distal fibula result from the same mechanism as an ankle sprain. If the physical examination reveals tenderness along the distal fibular growth plate, a growth plate fracture must be considered, even if the radiographs are negative. In this case, a short period of immobilization followed by repeat imaging in 2 weeks is appropriate.

Tibiocalcaneal part

Medial Ankle Sprains

Deltoid ligament Figure 30-40 Anatomy of medial ankle ligaments.

The main ligament on the medial side of the ankle is the deltoid ligament (Fig. 30-40). Deltoid injuries are typically caused by an eversion mechanism. Medial ankle examination is similar to that of the lateral ankle. Observation of gait usually reveals a limp, and gross observation of the ankle often reveals medial edema but no other deformity. Active motion may be severely restricted, and neurovascular status should be normal. Careful palpation of bony, tendinous, and ligamentous structures of the medial ankle include the deltoid ligament, medial malleolus, medial process of talus, neck of talus, medial cuneiform, cuboid, navicular, and medial ankle tendons (posterior tibialis, flexor digitorum longus, and flexor hallucis longus). Stress testing of the deltoid ligament is performed by an eversion stress test, usually performed with the ankle in neutral position. Amount of excursion compared to the opposite side and the end-point feel determine the severity of the injury. Deltoid function can also be assessed by stressing the ankle, translating it from medial to lateral and assessing for instability or mortis widening. Any offset increases the stresses on the articular cartilage and increases the risk of arthritis. Obtaining radiographs in the patient with medial ankle injury is decided on a case-by-case basis but should be done more readily than for the typical lateral ankle sprain. Treatment plans are similar to those for lateral ankle sprains. It is widely believed that medial sprains take longer to heal than their lateral counterparts.

Syndesmosis Ankle Sprains (High Ankle Sprains) The ankle syndesmosis is the area of the distal tibia-fibula joint. The five soft tissue structures in the syndesmosis region include the anterior tibiofibular, posterior tibiofibular, transverse tibiofibular, and interosseous ligaments and the interosseous membrane; of these, the anterior tibiofibular ligament is most often injured. Syndesmosis sprains account for 1% to 18% of ankle sprains, with a higher incidence in high-level athletes. Syndesmosis sprains are generally thought to take longer to heal than lateral or medial sprains (Hopkinson et al., 1990), and persistent ankle pain and persistent dysfunction are more common (Gerber et al., 1998); 626

Posterior tibiotalar part

Anterior tibiotalar part Tibionavicular part

(From Nicholas J, Hershman E. The Lower Extremity and Spine in Sports Medicine, vol 1, 2nd ed. St Louis, Mosby, 1995, p 424.)

s yndesmosis injuries are often associated with fractures. The mechanism of injury is different than for the more common lateral and medial sprains; syndesmosis sprains are most often caused by forceful external rotation and hyperdorsiflexion injuries. Physical examination often reveals an antalgic gait limp and anterolateral ankle swelling over the anterior tibiofibular ligament just proximal to the joint line. Ecchymosis is often a delayed finding and is usually noted proximal to the ankle joint, in contrast to that noted in lateral and medial sprains, which is often below the ankle and occasionally throughout the foot. Careful palpation reveals tenderness directly over the anterior tibiofibular ligament. Syndesmosis injuries may be present along with medial ankle injury, so tenderness over deltoid ligament may be noted as well. Be sure to palpate the proximal fibula, because extreme forced external rotation may lead to Maisonneuve’s fracture (proximal fibular fracture). Strength testing is often limited by pain, and neurovascular status remains intact. Special stress tests to evaluate the syndesmosis include the squeeze, external rotation, and dorsiflexion-compression tests. The squeeze test is performed by compressing the fibula and tibia above the midpoint of the calf (Hopkinson et al., 1990) (Fig. 30-41). The test is positive if compression causes pain in the region of the syndesmosis ligament. The external rotation test is performed with the knee at 90-degree flexion and the ankle in neutral position. An external rotation force is applied to the foot while stabilizing the remainder of the leg. Pain in the anterior tibiofibular region is a positive test. The external rotation test is thought to be the most reliable of the common clinical tests used to diagnose syndesmosis sprains. Because of the risk of concurrent fracture with syndesmosis sprains, radiographs should be obtained. Plain radiographs are adequate to assess for frank diastasis (widening between fibula and tibia). Stress radiographs may be necessary to discover latent diastasis. The three major radiographic considerations are the (1) tibiofibular clear space, the distance between medial border of fibula and lateral border of posterior tibia,


1

2

3

A

Figure 30-41 Squeeze test. (From Hopkinson WJ, St. Pierre P, Ryan IB, et al. Syndesmosis sprains of the ankle. Foot Ankle Int 1990;10:325-330. Copyright American Orthopedic Foot and Ankle Society, 1990.)

measured 1 cm above tibial plafond; (2) tibiofibular overlap, the maximum amount of overlap of distal fibula and anterior tibial tubercle; and (3) medial clear space, the distance between medial malleolus and medial border of talus, measured 1 cm below tibial plafond (Fig. 30-42). Additional testing such as CT scan can be helpful early in the workup to look for occult fracture and later to assess for heterotopic ossification, a common complication of syndesmosis sprains. MR scan is sometimes used and has a high sensitivity and specificity for detecting anterior and posterior tibiofibular ligament injuries (Oae et al., 2003). Initial treatment begins with protection of the joint, relative rest, ice, compression, and elevation. Various modalities to reduce swelling and inflammation can be used. Rehabilitation includes ROM exercises, strengthening and balance exercises, and proprioception training. Activities can be advanced when pain is reduced, and rehabilitation exercises can be performed pain-free. Return to full activities can be entertained when the patient has full motion, full strength, no tenderness on examination, and no functionally limiting pain. Latent diastasis can be treated nonoperatively if reduction can be achieved. Therapy includes immobilization with non–weight bearing followed by progressive weight bearing beginning at about 4 weeks and full weight bearing by 2 months. Surgery is needed if reduction cannot be achieved or if diastasis recurs despite immobilization. Frank diastasis is treated surgically. A common adverse outcome of syndesmosis sprain is heterotopic ossification. Plain radiographs are adequate to make the diagnosis in patients with persistent pain (Fig. 30-43). Affecting 25% to 90% of patients, heterotopic ossification may or may not be symptomatic. Ossification may cause pain without causing frank synostosis. The discomfort

B Figure 30-42 Normal anteroposterior radiograph of the ankle revealing a normal tibiofibular clear space (1), normal tibiofibular overlap (2), and normal medial clear space (3). Significant mortise widening is noted with widening of all three of these parameters. Note the distal fibula fracture. This injury is best treated with internal fixation of the fracture and stabilization of the ankle mortise with a syndesmosis screw. B, Football eversion injury shows widening medial mortise with associated deltoid tear, widening distal tibiofibular syndesmosis, high fibular fracture, and small posterior malleolus fracture (not seen here). (A courtesy James L. Moeller, MD; B from Nicholas J, Hershman E. The Lower Extremity and Spine in Sports Medicine, vol 1, 2nd ed. St Louis, Mosby, 1995, p 465.)

comes from an inflammatory response in early stages, then from pressure on adjacent bones. Fracture of the ossification is also a potential cause of pain. Frank synostosis can occur. Pain typically results from restricted tibiofibular motion, particularly during full ankle dorsiflexion. Conservative treatment may reduce the pain, but surgical excision may be required (Hopkinson et al., 1990; Taylor et al., 1992). 627

30


ltrasound and MRI are not routinely needed early on but U may be used to assess for partial tears, as well as assess the vascular integrity of the injured area. Ultrasound and MR changes in the tendon can persist even after functional recovery (Khan et al., 2003). Treatment of Achilles tendinopathy is similar to that for other forms of tendinopathy and includes ice treatment, relative rest, NSAIDs, stretching and strengthening programs, and proprioception exercises. An exercise program focused on eccentric training has been described and renders promising results in many cases (Alfredson et al., 1998). Most experts agree that corticosteroid injection should not be considered due to the risk of tendon rupture. For recalcitrant cases, treatments such as prolotherapy and extracorporeal shock wave therapy have been studied, but short-term follow-up and isolated reports of effectiveness are mixed. Platelet-rich plasma injections for chronic Achilles tendinopathy have no benefit over saline injections. Surgical debridement is reserved for chronic cases and involves debridement of the diseased tendon and may require tendon transfers for grafting.

Achilles Tendon Rupture Figure 30-43 Heterotopic ossification noted after syndesmosis ankle sprain. (Courtesy James L. Moeller, MD.)

Achilles Tendinopathy Achilles tendinopathy is a common problem, especially in running and jumping athletes. The Achilles tendon consists of the distal ends of the gastrocnemius and soleus muscles and attaches broadly across the posterior aspect of the calcaneus. Contraction of the Achilles results in plantar flexion of the ankle. Activities that cause eccentric loading of the tendon may result in tendonitis. Achilles tendonitis is considered an overuse injury. Patients present with pain in the posterior aspect of the distal lower leg or heel. Pain is worsened with push-off activities, such as walking up hills or stairs, running, or jumping. Examination reveals tenderness to palpation of the distal portion of the tendon. A palpable area of swelling and firmness may be noted as well as “wet crepitus” from fluid in the peritenon. Strength may be limited because of discomfort. This can be assessed by direct manual testing or by having the patient perform repeated single-foot toe-raise exercises. Assessment of the integrity of the Achilles tendon is essential and best done by the Thompson test. Asking the patient simply to plantar-flex the ankle actively is not sufficient because there are several secondary plantar flexors. Lay the patient prone on the examination table with the knee flexed to 90 degrees and the ankle in neutral position. Squeeze the midgastrocnemius area and observe for passive ankle plantar flexion. If the Achilles is intact, the ankle will plantar-flex (negative test). If the Achilles is torn, the ankle will remain in neutral position (positive test). Radiographs generally are not necessary to make an accurate diagnosis of Achilles tendinopathy or to initiate treatment. X-ray films are considered in chronic cases, primarily to rule out calcific tendinopathy and Haglund deformity (bump on back of calcaneus near Achilles insertion). 628

Tears of the Achilles tendon are most often encountered in males 40 to 60 years old. The most common mechanism of injury is sudden, forceful eccentric loading of the tendon. This can occur from a sudden forceful push-off from a single foot, or landing on a single foot. Patients present due to sudden onset pain in the posterior heel and decreased pushoff strength. Patients often describe a feeling of being kicked or hit in the heel, often hearing or feeling a pop at the time of injury. Examination may reveal a palpable gap in the tendon, usually distally. Thompson’s test is positive, with no ankle plantar flexion when the examiner squeezes the calf. Imaging studies are not typically needed to make an accurate diagnosis of Achilles tendon rupture. Both surgical and nonsurgical treatment options exist (McComis et al., 1997; Weber et al., 2003). Patient selection and including the patient in the decision-making process are important. Generally, younger patients who desire or require greater posttreatment push-off power are likely to be good surgical candidates, whereas older patients or patients who require less push-off power are nonsurgical candidates. Nonoperative risk of repeat rupture is as high as 10%, versus up to 2% with surgery. Skin necrosis of the surgical wound occurs in 5% to 10% of patients. Conservative treatment entails a period of immobilization accomplished through casting or brace use, usually 8 to 10 weeks; early weight bearing is controversial. After immobilization, progressive rehabilitation to regain motion, strength, and proprioception is initiated. Surgery is associated with improved push-off power and reduced rate of repeat rupture and generally allows for the best functional recovery (Wong et al., 2002).

Plantar Fasciitis Plantar fasciitis is the most common cause of plantar heel pain in active individuals. The plantar fascia is a fibrous band of tissue that originates at the medial calcaneal tubercle, fans out across the plantar aspect of the foot, and then splits before inserting into the plantar aspects of the proximal


phalanges. Plantar fasciitis is an overuse injury often seen in people who stand for prolonged periods, as well as in runners and regular exercisers. Many believe plantar fasciitis is an inflammatory condition, but it is more likely caused by chronic changes and microtears of the fascia. Patients present with plantar heel pain. Pain has often been present for several months before presentation. The pain is often described as sharp and stabbing and tends to be worst in the morning, on arising from prolonged sitting, and after standing for prolonged periods. Other symptoms, such as bruising, swelling, weakness, numbness, and tingling, are uncommon. The primary finding on physical examination reveals tenderness over the origin of the plantar fascia. Treatment protocols are variable, and it may take several months for the patient to feel significant pain relief. Most treatment plans include plantar fascia stretching, ice or ice massage, heel cushioning, and analgesic medication. NSAIDs are often used, but are helpful most likely because of their analgesic, not anti-inflammatory, effects. Other common treatment options include night splints, physical therapy, orthotic devices, and cortisone injection. Cortisone injection reduces pain from plantar fasciitis, but the mechanism is unclear (Hunt and Sevier, 2004). Cortisone is a potent antiinflammatory, but as previously stated, chronic plantar fasciitis is probably not an inflammatory problem. Risks with cortisone injection include plantar fascia rupture and necrosis of the plantar fat pad, the natural heel cushion. These adverse outcomes should be reviewed with patients before injection. New modalities for the treatment of plantar fasciitis are under investigation. Extracorporeal shock wave therapy has shown mixed results (Rompe et al., 2002, 2003). Prolotherapy and autologous blood injection involve injecting substances into the area of pathology. Dry needling is also being

studied. None of these options has proved to be consistently helpful. Surgical intervention is sometimes needed in recalcitrant cases.

Metatarsal Fractures Nondisplaced fractures of the midshaft and distal portions of the metatarsals are treated with immobilization. Short-leg casting and immobilizer boots can lead to adequate healing in 6 to 8 weeks in most cases. Postoperative shoe use without formal immobilization can also lead to adequate healing of metatarsal fractures, although the risk of adverse outcome is higher. Displaced, angulated, and rotated fractures may require operative fixation. Fractures of the proximal portion of the metatarsal (first through fourth metatarsals) should be approached with great care. Nondisplaced fractures may be associated with injury to the intermetatarsal ligaments, leading to widening of these joints; surgical consultation is recommended in these cases. If there is no apparent injury to the tarsometatarsal (Lisfranc) joint, cast immobilization typically leads to adequate fracture healing. Fractures of the base of the fifth metatarsal deserve special discussion. A watershed area of blood flow in the proximal portion of the fifth metatarsal puts it at particular risk for malunion and nonunion. Avulsion fractures off the most proximal portion of the bone have an opportunity to heal with conservative management. Fractures that occur in the watershed area, so-called Jones fractures, have a high chance for malunion and nonunion that should be discussed with the patient. Jones fractures occur in the proximal one third of the metatarsal and do not involve the tarsometatarsal joint. Screw fixation of Jones fractures often leads to more acceptable outcomes.

EVIDENCE-BASED SUMMARY • E arly mobilization with an external support device after ankle sprain leads to better short-term outcomes (reduction of pain and return to work/ sport activities) compared to early immobilization; long-term outcomes are similar (Eiff et al., 1994; Karlsson et al., 1996; Kerkhoffs et al., 2004) (SOR: A). • Use of an external ankle brace after ankle sprain reduces the risk of recurrent sprain. Evidence also supports balance and proprioception training for reducing risk of recurrent sprain (Bahr et al., 1997; Surve et al., 1994) (SOR: B). • An eccentric training program is effective in treating chronic Achilles tendinopathy (Alfredson et al., 1998) (SOR: B). • Surgery for acute Achilles tendon ruptures reduces the risk of repeat rupture compared to nonsurgical treatment but produces a significantly higher risk of other complications, including wound infection (Khan et al., 2004) (SOR: A). • Corticosteroid injection can reduce plantar fasciitis pain in the short term (Hunt and Sevier, 2004) (SOR: B). • For acute Jones fractures in recreationally active patients, early intramedullary screw fixation results in lower failure rates and shorter times to both clinical union and return to sports than non-weight-bearing short-leg casting (Vu et al., 2006) (SOR: B).


Web Resources Shoulder www.shoulderdoc.co.uk/article.asp?section=497 Review of the shoulder exam with specific instructions on physical exam.

http://emedicine.medscape.com/article/1260953-overview http://orthoinfo.aaos.org/topic.cfm?topic=A00072 Clavicle fracture http://orthoinfo.aaos.org/topic.cfm?topic=a00033 www.eorthopod.com/node/10838 AC sprain. 629

30


www.eorthopod.com/node/10847 SC sprain. http://emedicine.medscape.com/article/92974-overview http://orthoinfo.aaos.org/topic.cfm?topic=A00032 Shoulder impingement. www.emedicinehealth.com/rotator_cuff_injury/article_em.htm http://orthoinfo.aaos.org/topic.cfm?topic=A00406 Rotator cuff tear. http://orthoinfo.aaos.org/topic.cfm?topic=A00529 Shoulder instability.

Elbow http://emedicine.medscape.com/article/1231903-overview http://orthoinfo.aaos.org/topic.cfm?topic=A00068 Lateral tendinopathy http://emedicine.medscape.com/article/327860-overview www.mayoclinic.com/health/golfers-elbow/DS00713 Medial tendinopathy

Wrist and Hand www.mayoclinic.com/health/carpal-tunnel-syndrome/DS00326 Carpal tunnel syndrome. www.mayoclinic.com/health/de-quervains-tenosynovitis/DS00692 www.handuniversity.com/topics.asp?Topic_ID=45 DeQuervain’s tenosynovitis. www.mayoclinic.com/health/trigger-finger/DS00155 Trigger finger. http://orthoinfo.aaos.org/topic.cfm?topic=a00412 Distal radius fracture. http://orthoinfo.aaos.org/topic.cfm?topic=A00012 www.handuniversity.com/topics.asp?Topic_ID=30 Scaphoid fracture.

Knee http://orthoinfo.aaos.org/topic.cfm?topic=A00212 Degenerative osteoarthritis. http://orthoinfo.aaos.org/topic.cfm?topic=A00197 Joint infection.

630

www.mayoclinic.com/health/patellar-tendinitis/DS00625 Patellar tendinitis. www.webmd.com/a-to-z-guides/patellofemoral-pain-syndrome-topicoverview Patellofemoral pain. http://orthoinfo.aaos.org/topic.cfm?topic=a00358 Meniscus tear. www.webmd.com/a-to-z-guides/anterior-cruciate-ligament-acl-injuriestopic-overview http://orthoinfo.aaos.org/topic.cfm?topic=A00297 Ligament injury.

Ankle and Foot www.emedicinehealth.com/ankle_sprain/article_em.htm http://orthoinfo.aaos.org/topic.cfm?topic=a00150 Ankle sprain. www.mayoclinic.com/health/achilles-tendinitis/DS00737 Achilles tendinitis. www.emedicinehealth.com/achilles_tendon_rupture/ article_em.htm www.mayoclinic.com/health/achilles-tendon-rupture/DS00160 Achilles tendon rupture. www.mayoclinic.com/health/plantar-fasciitis/DS00508 Plantar fasciitis. http://emedicine.medscape.com/article/399372-overview Metatarsal fracture.

Splinting and Casting http://intermed.med.uottawa.ca/procedures/cast/#02

C H A P T ER

31

Back: Cervical and Thoracolumbar Spine Minal Patel and Krupa Shah

Chapter contents Cervical Spine Anatomy History Physical Examination Diagnostic Tests Torticollis Whiplash Cervical Strains and Sprains Cervical Radiculopathy

631 631 631 631 634 634 634 634 634

Cervical Spine The cervical spine provides support and stability for the head. Articulation at the joints of the vertebrae allows for the range of motion of the head. The spine is also the route through which the nerve roots travel out from the spinal canal to the extremities. As with back pain, chronic neck pain or disorders related to limited function from neck problems are common reasons for office visits. A careful history and examination help elucidate the cause and the level and extent of compromise affecting cervical function.

Anatomy The cervical spine is made up of seven vertebrae (C1-C7). A typical vertebra has a body and neural arch. The neural arch is made up of two pedicles and two vertebrae; the laminae meet at the spinous process posteriorly. A transverse process projects out laterally on each side of the pedicle and lamina (Fig. 31-1). The articular processes on the superior and inferior parts of each vertebra at the junction of the pedicle and lamina meet at the facet joints. The first two vertebrae have distinct features. The atlas, C1, articulates with the occipital bone and has no spinous process or body. The axis, C2, has an odontoid process that articulates with C1 (Fig. 31-2); much of the rotational function of the neck occurs at this joint. C7 has a long spinous process, resulting in a palpable prominence below the skin in the lower neck. Several ligaments stabilize the neck. The anterior and posterior ligaments support the entire vertebral column (Fig. 31-3). The spinous process of each vertebra is attached by the ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10031-2

Thoracolumbar Spine Anatomy History Physical Examination Diagnostic Testing Low Back Pain Lumbar Disk Syndromes Thoracolumbar Vertebral Compression Fractures Spinal Stenosis Scoliosis

636 636 636 636 637 638 641 644 645 646

nuchal ligament to the neck and the interspinous ligaments. Intervertebral disks separate each vertebra. Their function is to distribute the pressure over a wider area of the vertebra and allow mobility. Each disk consists of a gelatinous central nucleus and outer fibrous annulus fibrosus. Eight pairs of nerves originate from the cervical spine. The first seven nerve roots exit the spinal canal above the corresponding vertebra, and the eighth nerve root exits from below C7 (Fig. 31-4).

History The relevant history includes age of the patient, location of any pain, acute or gradual onset, radiation and duration of pain, and any related associated symptoms that indicate whether the pain is of cervical origin or referred from another condition. An older patient is more often affected by arthritis and a younger person by musculoskeletal pain. Rest or nighttime pain may be a symptom of a tumor or infection. Other symptoms include neck stiffness, headache, and symptoms of radiculopathy such as tingling, numbness, and loss of strength in the upper extremities. Where the pain is caused by nerve entrapment, the pain may radiate along the distribution of the involved nerve. Events leading up to the presentation may also give clues to the problem.

Physical Examination The neck examination includes inspection for any neck lesions, masses, or scars as well as posture and normal cervical lordosis, characterized by a slight anterior curvature (Fig. 31-5). The neck is palpated for points of tenderness.

31

Back: Cervical and Thoracolumbar Spine

S A

N

P

I

L

A P T B

Figure 31-1 Typical cervical vertebra. S, Spinous process; L, lamina; A, articular facet; P, pedicle; T, transverse process; B, body. (Redrawn from Mercier L.

Figure 31-3 Ligaments of the cervical spine. A, Anterior longitudinal ligament; P, posterior longitudinal ligament; N, nuchal ligament; I, interspinous ligament. (Redrawn from Mercier L. Practical Orthopedics, 5th ed. St Louis, Mosby, 2000, p 27.)

Practical Orthopedics, 5th ed. St Louis, Mosby, 2000, p 27.) C1 I II 2 II III 3 III 4 IV 5 IV V V 6 VI 7 VI 8 VII T1 VII T1 T1 2 3 II II 4 I

III

V

III

5

IV

6 7 8

VII VIII

10

IX

11

IX X

5 6

VI

9

VIII

4

V

VII

12

L1 2 3 4 XII 5

XI

S1

T1 2 3

IV

VI

C1 2 3 4 5 6 7 8

7 8 9

X

10

XI

11

XII

12

L1

L1

L1

II

2

II III

3

III IV IV V

4 V

5 Figure 31-2 1, Axis. 2, Atlas and transverse ligament (T). 3, Articulation of the atlas and axis. (Redrawn from Mercier L. Practical Orthopedics, 5th ed. St Louis, Mosby, 2000, p 27.)

S1 2 3 4 5 Coc. I Figure 31-4 Spinal cord and nerve roots in relation to the vertebrae. (Redrawn from Brinker MR, Miller MD. Fundamentals of Orthopedics. Philadelphia, Saunders, 1999, p 242.)

632

Back: Cervical and Thoracolumbar Spine Neutral 0°

1 2 3 Flexible lordosis

4 5 6 7

90°

90°

A

1 2

Neutral 0°

3

4 5 6 7

Fixed kyphosis

8

Line of gravity

90°

90°

B

9

Neutral 0°

10 11 POSTERIOR

ANTERIOR 12 1 90° 2

C 3

Figure 31-6 Range of motion. A, Flexion. B, Lateral flexion. C, Rotation. Flexible lordosis

4

(Redrawn from Carr AJ, Harnden A. Orthopedics in Primary Care. Newton, Mass, Butterworth-Heinemann, 1997, p 56.)

Table 31-1 Normal Range of Movement: Neck (Cervical Spine)

5 Center of gravity

Sacrum

90°

Fixed kyphosis

Coccyx Figure 31-5 Vertebral spine. Note that thoracic spine has relatively fixed kyphosis and lumbar spine relatively flexible lordosis. (Redrawn from Brinker MR, Miller MD. Fundamentals of Orthopedics. Philadelphia, Saunders, 1999, p 241.)

The range of movement is assessed by observing forward flexion with chin tilted down toward the chest and backward extension with the head tilted backward so that the eyes are looking toward the ceiling (Fig. 31-6). Lateral flexion to the right and left is the lateral bending of the neck, pointing the ear toward the shoulder on the same side. Lateral rotation

Motion

Range

Flexion

0-45 degrees

Extension

0-45 degrees

Lateral flexion

0-45 degrees

Rotation

0-60 degrees

Modified from Carr AJ, Harnden A. Orthopedics in Primary Care. Newton, Mass, Butterworth-Heinemann, 1997.

to the right and left is the chin turned toward each shoulder while the head is kept upright (Table 31-1). Examination should also include examination of the extremities. Inspection of the upper limbs may reveal muscle wasting or fasciculations. A detailed examination of the nervous system includes assessment of the power and tone of the muscles, reflexes, and sensory system, using sharp and light touch. Mapping the sensory loss by dermatomes and demonstrating asymmetry of deep tendon reflexes may show the cervical level with nerve compression. A complete general 633

31


examination, including the head, neck, lower extremities, and gait, allows for evaluation of other potential causes and effects of neck problems. Specific tests to evaluate the cervical spine also include the axial compression test, which may increase symptoms of radicular pain. The distraction test may relieve radicular symptoms. Spurling’s test may produce pain on the same side as nerve root encroachment.

c areful general examination of the head and neck, looking for a cause. Diagnosis may be apparent from the history and physical examination. Radiographs of the cervical spine may be obtained, if indicated, to rule out a vertebral cause. Management includes referral for emergency evaluation and treatment of traumatic injury and retropharyngeal abscess. Pain is relieved and the underlying cause treated. Persistent pain requires further evaluation.

Diagnostic Tests Diagnostic tests include radiographs of the cervical spine. Computed tomography (CT) may assess the bone further, and magnetic resonance imaging (MRI) is useful to assess the soft tissue, especially with associated neurologic symptoms.

Torticollis Key Points • Torticollis may be congenital or acquired. • Congenital torticollis may be characterized by a palpable tumor in the sternomastoid muscle in some cases. • Acquired torticollis may be caused by a spinal tumor. • Traumatic injury and retropharyngeal abscess require emergency treatment. • Management of acquired torticollis includes treating the underlying cause.

Torticollis, also called wry neck, is characterized by contraction of the sternomastoid muscle on one side of the neck, in which the head is tilted to the same side as the contracted muscle, and the chin is rotated to the opposite side. The condition may be congenital or acquired. Congenital torticollis is caused by the contraction of the sternomastoid muscle. The cause is unclear but may be associated with birth trauma or an abnormal fetal uterine position causing local muscle ischemia. Children with hip dysplasia and breech delivery have a higher incidence of torticollis. Also, delayed development of the face on the affected side may result in facial asymmetry and changes in the cervical vertebrae. On examination, a small lump may be palpable in the muscle, known as a sternomastoid tumor. In mild cases, treatment is initiated early and includes gentle stretching exercises several times daily. Supervised physical therapy may be considered. Surgery may be considered in special circumstances with patients who do not respond to conservative treatment. The procedure includes surgical release of the sternomastoid muscle, followed by corrective exercises. Acquired torticollis usually does not involve contraction of the sternomastoid on the same side of the neck. The torticollis has a particular cause, such as upper respiratory tract infections, cervical lymphadenitis, trauma minor neck injury, unilateral subluxation of the vertebrae, or fractures, as well as unusual causes such as spinal tumor or retropharyngeal abscess. Torticollis may also be seen in relation to ocular disturbance, such as strabismus, known as ocular torticollis. History includes duration and onset of symptoms, whether sudden or gradual, associated symptoms (e.g., fever, sore throat), and history of injury. Clinical examination, in addition to the clinical appearance of torticollis, requires 634

KEY TREATMENT Treatment of congenital torticollis includes gentle stretching exercises; surgical treatment may be considered in special circumstances (Do, 2006) (SOR: C).

Whiplash Whiplash is a hyperextension injury. The injury is caused by abnormal stretching of the muscles and soft tissue structures. There may be an associated disk herniation and tracheal and esophageal injury, resulting in hoarseness and dysphagia. Clinical features are pain in the lower neck and shoulders radiating to the occipital area, which may cause headaches. The neck pain may continue for weeks to months. The patient may have tenderness on palpation of the neck, perhaps some limitation in range of movement, and usually a normal neurologic examination. Radiographs are usually normal. Treatment is conservative with rest, a cervical collar, cold compresses, and pain relief, followed by simple range of motion (ROM) exercises. If symptoms improve, structured physical therapy may be considered.

Cervical Strains and Sprains Cervical strains and sprains are characterized by pain in the neck because of irritation and spasm of muscles at the back of the neck. Common related factors are poor posture (e.g., while working or studying), carrying heavy bags on one shoulder, emotional or physical stress, and trauma. The patient has a history of pain in the lower neck and upper back; stiffness in the neck, back, and shoulders; and perhaps a new work environment, working in a certain posture (e.g., at computer), and trauma. Clinical findings include tenderness posterior to neck, with or without ROM limitation. Diagnosis may be apparent from the history and physical examination. Uncomplicated pain is managed by conservative treatment and correction of causative factors, such as changes in associated environmental factors (e.g., adjustment of height of desk or chair, avoiding straps on shoulders). Stress reduction is beneficial to aid reduction of muscle tension. Warmth applied to the neck is helpful, as are ROM exercises, pain relief, and referral to physical therapy. Persistent symptoms, history of trauma, or neurologic signs in the extremities require further evaluation with radiography.

Cervical Radiculopathy Radiculopathy occurs when nerve root compression at the neck or spine results in pain, tingling, and numbness, with or without loss of function in the area supplied by the affected nerve. Common causes of cervical radiculopathy are neural


foramen narrowing, usually caused by cervical arthritis in older adults, and cervical disk lesion caused by disk degeneration or herniation. Disk degeneration results in loss of disk space, with closer approximation of the vertebrae on either side of the involved disk space and subsequent impingement on the neural foramen (Fig. 31-7). The decrease in size of the neural foramen results in nerve root compression. The C5-C6 and C6-C7 disk spaces are more often affected. Disk herniation also occurs more often in these disks (Fig. 31-8). Some of the gelatinous pulp protrudes through the annulus fibrosus at the weakest point, usually where the posterolateral longitudinal ligament crosses the disk. In a smaller disk herniation, mild local pain may be caused by pressure on

the posterior ligament. A larger disk herniation may impinge on the nerve and may be posterolateral or central herniation with resultant radicular symptoms. The patient has a history of pain radiating to the shoulder or down the upper extremity, which may be aggravated by coughing, sneezing, or straining; paresthesias of the fingers; and less often, weakness in the extremity. There may be a history of prior trauma. Cervical radiculopathy on examination may reveal tenderness on the neck, limitation in certain movements of the neck, focal neurologic findings such as sensory loss in the dermatome pattern corresponding to the distribution of the affected nerve root, and asymmetric tendon reflexes in the upper extremities (Fig. 31-9).

Degenerate disc Osteophytes Narrowed foramen Osteophytes

A

B

Figure 31-7 Osteoarthritis of cervical spine. A, Initial degeneration and narrowing of intervertebral disk, with formation of osteophytes anteriorly. B, Later, posterior or facet joints are affected; articular cartilage is worn away, and marginal osteophytes may encroach on the intervertebral foramen. (Redrawn from Adam JC, Hamblen DL. Outline of Orthopedics, 13th ed. New York, Churchill Livingstone, 2001, p 159; and Anderson BC. Office Orthopedics for Primary Care: Diagnosis and Treatment, 2nd ed. Philadelphia, Saunders, 1999, p 266.)

Spinal cord

Nerve Disc

A

B

Figure 31-8 Prolapsed cervical disk. A, Posterolateral prolapse, with compression of the issuing nerve. B, Much less common central prolapse, with impingement on the spinal cord. (Redrawn from Adam JC, Hamblen DL. Outline of Orthopedics, 13th ed. New York, Churchill Livingstone, 2001, p 163.)

C6 C7 C8 T1

C6

C7

T1 C8 Figure 31-9 Volar and dorsal dermatome patterns of the forearm and hand. Pain and paresthesias may radiate into these areas when the affected nerve root is compressed. Note that extremity symptoms as a result of disk disease are almost always unilateral. (Redrawn from Mercier R. Practical Orthopedics, 5th ed. St Louis, Mosby, 2000, p 29.)

635

31


General examination should include the lower extremities and gait. Axial compression testing may reproduce the pain. Diagnostic tests include radiographs of the cervical spine, which may appear normal or may show loss of normal cervical lordosis, narrowing of the disk space, and bone spurs with foramen encroachment. If the patient has neurologic symptoms, MRI identifies soft tissue structures and may show displacement of the disk. CT may also be performed. Treatment relieves pressure on the affected nerve and is mainly conservative, including rest, pain relief, stress reduction, and short-term muscle relaxants. Patients with persistent symptoms may need structured physical therapy and referral for specialist evaluation. Neurologic signs and symptoms and loss of strength are also indications for referral to neurosurgery. A few patients require surgical intervention.

Anterior longitudinal ligament Supraspinous ligament Interspinous ligament

Lamina

KEY TREATMENT

Ligamentum flavum

Whiplash is usually managed conservatively (Binder, 2007) (SOR: C). Uncomplicated pain in cervical strains and sprains is managed conservatively (Binder, 2007) (SOR: C). Range of motion exercises may be beneficial for uncomplicated cervical strain or sprain (Cochrane Review, 2005) (SOR: A). Treatment of cervical radiculopathy is usually conservative (Binder, 2007) (SOR: C).

Articular capsule Cut surface of pedicle Posterior longitudinal ligament Intervertebral disc

Thoracolumbar Spine The thoracolumbar spine is the cause of frequent patient visits to a family physician. Back pain is the most common and expensive diagnosis of patients age 30 to 60 years. It is responsible for lost time at work, lost wages, increased surgeries, litigation expenses, and economic and psychosocial burden. Appropriate and timely diagnosis and treatment can prevent most of the sequelae of back pain.

Anatomy The back is supported by 12 thoracic vertebrae (T1-T12) and five lumbar vertebrae (L1-L5). The lumbar vertebrae are larger and thicker than the cervical and thoracic vertebrae because they carry the most amount of body weight and are subject to the largest forces and stresses along the spine (see Fig. 31-5). The alignment of thoracolumbar vertebrae with their disk and ligament is similar to the cervical spine. The joints between the vertebrae, ligaments, and muscles of the back stabilize the vertebral column. The major longitudinal ligaments connecting the vertebrae are the anterior and posterior ligaments (connect vertebral bodies), ligamentum flavum (between adjacent laminae), and supraspinous and interspinous ligaments (connect spinous processes). The anterior and posterior longitudinal ligaments and supraspinous ligament run along the entire length of the vertebral column and support the spine. The interspinous ligament and ligamentum flavum provide additional posterior stability to the spine (Fig. 31-10). Intervertebral disks make up about one third of the length of the spine. The normal movements of thoracolumbar spine are forward flexion (by asking the patient to touch toes), extension, lateral bending, and symmetric rotation (Fig. 31-11 636

Figure 31-10 Supporting ligaments of the spine. (Redrawn from Brinker MR, Miller MD. Fundamentals of Orthopedics. Philadelphia, Saunders, 1999, p 242.)

and Table 31-2). Flexion and extension are limited in the thoracic region because of the rib cage.

History The patient history of conditions in the thoracolumbar spine is similar to the cervical spine. A complete description of the onset, duration, nature, severity of symptoms, and aggravating and relieving factors should be obtained. Other important history includes medical history (including previous injuries) and psychosocial stressors at work or home. Symptoms may require urgent referral and workup and include unremitting back pain, urinary or bowel paralysis, weakness, fever, and weight loss.

Physical Examination The physical examination should begin with observing the patient in the sitting and standing positions from the back as well as the front. Observing the patient moving around, dressing, and undressing may also help in confirming the severity of the symptoms. Muscle spasms, swellings, deformities, unusual markings, redness, and hair patches should be noted. The patient’s posture and gait should be observed. The area palpated includes soft tissues and bone structures for tenderness and swellings. It helps to isolate the level of the lesion. ROM should be observed. A thorough neurologic examination should be performed to assess for sensations, deep tendon reflexes, and muscle strength. Examining the

Back: Cervical and Thoracolumbar Spine Neutral

Neutral

0°

0°

1

1. Degrees of inclination of trunk (note reversal of lumbar curve) 2. Level of fingertips to leg 3. Distance between fingertips and floor

2 3

A

B 0°

0° 30°

35°

90°

C

90°

D

Figure 31-11 Methods of measuring flexion. A, Flexion, zero starting point. B, Measuring flexion. C, Extension. D, Lateral bend. (Redrawn from Carr AJ, Harnden A. Orthopedics in Primary Care. Boston, Butterworth-Heinemann, 1997, p 70.)

Table 31-2 Normal Range of Movement: Thoracolumbar Spine

Motion

Range

Flexion

0-80 degrees

Extension

0-20 degrees

Lateral bend

0-35 degrees

Rotation

0-45 degrees

Modified from Carr AJ, Harnden A. Orthopedics in Primary Care. Newton, Mass, Butterworth-Heinemann, 1997.

rectal tone, perineal sensations, and reflexes is essential if the patient has significant nerve root pain and weakness and chord compression is suspected. Special tests are done for determining nerve root impingement. The straight-leg raise test is performed with the patient lying on the back on the examination table. Passive lifting of the leg with the knee extended produces pain radiating down the posterior or lateral aspect of the leg, distal to the knee and often into the foot. Dorsiflexion of the foot (Lasegue’s test) will increase these symptoms (Fig. 31-12). The bowstring

sign is performed after a straight-leg raising test by flexing the knee to reduce radicular pain. Compression is then applied to the popliteal fossa. Return of radicular pain is considered a positive sign (Fig. 31-13). Crossed straight-leg raise is done by performing a straight-leg raise of the unaffected extremity. If the symptoms are produced on the affected extremity, the test is positive for central disk herniation. Femoral nerve traction test aids in the diagnosis of disk herniation that affects the upper lumbar spine (L2, L3, and L4). The patient lies on the stomach on the examination table with the knee flexed to 90 degrees. The physician then extends the patient’s hip by lifting it off the table (Fig. 31-14). The test is positive if it produces radicular pain. The peripheral pulses are palpated, and any abnormalities in the vascular status of the extremities are noted.

Diagnostic Testing Diagnostic testing for thoracolumbar conditions is similar to that for the cervical spine. Plain radiographs (AP, lateral, and oblique views) can be obtained (Fig. 31-15). CT, MRI, or myelography may be indicated in patients with worsening neurologic deficits or a suspected systemic cause of back pain, such as infection or neoplasm. These imaging studies are also useful when referral for surgery is considered. 637

31


A

B

Figure 31-12 A, Straight-leg raising test. B, Lasegue’s test. (From Reider B. The Orthopedic Physical Examination. Philadelphia, Saunders, 1999, pp 364, 365.)

B

A

Figure 31-13 Bowstring sign. (From Reider B. The Orthopedic Physical Examination. Philadelphia, Saunders, 1999, p 365.)

Low Back Pain Key Points

Figure 31-14 Femoral nerve stretch test. (From Reider B. The Orthopedic Physical Examination. Philadelphia, Saunders, 1999, p 367.)

638

• A careful history and physical examination are essential in diagnosing any case of low back pain. • Unremitting back pain and loss of bowel control require emergency assessment. • Radiographs and laboratory tests are generally unnecessary with low back pain. • With acute low back pain The therapeutic goal is to make the patient ambulatory and return to premorbid status. • Recurrence of back pain and functional limitation can be prevented with appropriate conservative management, early mobilization, exercise, return to normal activity, and patient education. • Exercise and physical therapy are the most effective treatment for chronic back pain.


A B

C

D

Figure 31-15 Plain radiographs of the lumbar spine. A, Anteroposterior view. B, Lateral view. C and D, Right posterior oblique (RPO) and left posterior oblique (LPO) views. b, Body of vertebra; f, intervertebral (neural) foramen; if, inferior facet; l, lamina; p, pedicle; pi, pars interarticularis; s, spinous process; sf, superior facet; t, transverse process (denotes interpedicular distance). (From Brinker MR, Miller MD. Fundamentals of Orthopedics. Philadelphia, Saunders, 1999, p 249.)

639

31


• With chronic low back pain, the therapeutic goal is to provide a long-term increase in function or a decrease in pain and disability. • Psychological support and therapy may provide relief in chronic low back pain.

Low back pain is the most common cause of both acute and chronic pain. In the United States, approximately 90% of adults experience back pain at some time in their life, and 50% of working persons have back pain annually. As many as 90% of patients with acute back pain return to work within 3 months, but 10% experience symptom recurrence and functional limitations and eventually develop chronic pain. Low back pain is one of the leading causes of both disability and absenteeism from work. Less than half of patients out of work for more than 6 months secondary to low back pain will ever work again, creating an enormous financial strain on the patient, family, and community. In primary care practice the specific anatomic cause of low back pain is usually not known; only a small percentage of patients have an identifiable underlying etiology. Less than 2% of patients have disk herniation, and only rarely do patients have a life-threatening condition. The most common cause of back pain is the lumbosacral strain following a single action or multiple lifting or twisting maneuvers. Factors that predispose to low back strain include repetitive use of poorly toned muscles, obesity, smoking, poor work habits, high-heeled shoes, and lack of physical activity. Most patients with acute low back pain improve in 2 to 4 weeks. Patients who progress to chronic back pain spend much time and money to become “pain free.”

Assessment and Clinical Features Most causes of low back pain are benign, but a thorough history and physical examination can identify a small percentage of patients with serious infection, malignancy, rheumatologic disease, or neurologic disorder. These serious conditions need immediate further evaluation. The review of systems includes constitutional symptoms, night pain, bone pain, morning stiffness, visceral pain, and claudication. The history includes exact location of the pain and the day, time, and activity involved in the initial back pain. The patient’s occupational risk assessment includes heavy lifting, prolonged sitting or standing, bending or twisting, and work with heavy, vibrating equipment. Patients often point to a well-localized area of the lower part of the back. Patients may have paraspinal muscle spasm and tenderness. Any movement may be painful, and the patient may walk in a slightly flexed position. Muscle spasm may be severe enough to cause loss of normal lumbar lordotic curve. If the strain is unilateral, the back may tilt to the affected side secondary to muscle spasm. The patient has reduced ROM, especially flexion and lateral bending secondary to pain. Neurologic examination should reveal no signs of radiculopathy in a normal back exam. At subsequent visits, further assessment and evaluation are based on the history of persistence, recurrence of pain, and functional limitations. Functional overlay and signs of excessive pain behavior should be sought. Complaints without objective findings suggest a psychological role in symptom formation; psychological testing and behavior intervention may be needed. During further encounters, psychosocial obstacles to recovery should be explored. Patients whose work provides 640

lower job satisfaction are more likely to report back pain and have a delayed recovery. Patients with affective mood disorders (e.g., depression) or substance abuse problems are more likely to have chronic pain and difficulty with pain resolution.

Diagnostic Testing Radiographic imaging in uncomplicated cases of lumbosacral strain is rarely necessary and usually does not correlate with the patient’s pain. Most people older than 40 years have anatomic defects on plain films of the spine. If the low back pain is probably more than a lumbosacral strain or has persisted for more than 6 weeks, radiographs may be helpful. CT or MRI should be reserved for low back pain accompanied by moderate to severe radicular symptoms, in the presence of motor weakness and neurologic deficits.

Treatment Once it is determined that the patient has an uncomplicated lumbosacral strain, the goal of therapy for acute low back pain is to make the patient ambulatory and return to premorbid status. This goal should be explained to the patient, whose active participation is critical. Successful treatment depends on the patient’s understanding of the disorder and the prevention of repeat injury. Patients should remain active to assist recovery, compared with short-term bed rest. Family physicians should begin with conservative therapy. Most patients with acute low back pain improve with conservative management within 2 to 4 weeks. Early mobilization and return to normal activities should be encouraged. Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are mainstays of pharmacologic therapy for acute low back pain. Muscle relaxants are effective for short-term relief. Short-term use of a narcotic could be considered for relief of severe, acute pain. As the pain permits, gentle stretching exercises should be initiated (Fig. 31-16). Patients should taper use of the analgesics while gradually increasing their normal activities. Extremes of twisting, bending and tilting should be avoided. If these are work-related activities, the patient may require a change to “light duty.” Teach techniques to lift heavy objects and educate patients about maintaining proper posture (Fig. 31-17). Most patients recover and require no additional evaluation. Prevention of repeated back injuries is then the focus. The patient should be instructed on overall body conditioning. Exercises that do not stress lower back muscles include swimming, water aerobics, and low-impact walking. Rehabilitation exercises and aerobic conditioning for trunk extensors, abdominal muscles, and back strengthening (modified sit-ups, weighted side bends, gentle extensions) should become part of the patient’s daily routine (Fig. 31-18). The patient with chronic low back pain remains a challenge. The ultimate goal in chronic pain management is longterm increase in function or decrease in pain and disability. Typically these patients already had multiple therapies for acute back pain. Assessment of social and psychological factors may help identify a pain etiology that affects treatment. Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity. Exercise is as effective as conventional physiotherapy. Exercise and physical modalities are the mainstays of therapy. Heat, cold, massage, ultrasound, and muscle stimulation

Back: Cervical and Thoracolumbar Spine Back-stretching exercises play a vital role in the treatment of lumbosacral muscle spasms. The lower back is heated for 15 to 20 minutes. Sets of 10 to 20 stretches, each held for 5 seconds, are performed on each side. The muscles are kept relaxed. Rest for 1 to 2 minutes between exercises. Mild muscle soreness is to be expected. Severe pain, electric-like sharp pain, or severe muscle spasms suggest overstretching.

Knee-chest pulls Bring your knee slowly up to your chest, holding it in place with your hands. Relax the buttock and back muscles. Do the left side, then the right side, and then both simultaneously (curling up in the fetal position).

Pelvic rocks With knees bent, rotate your pelvis forward and then backwards. The abdominal muscles do the work, as the back muscles are relaxed. Caution: Do not overextend when arching the back! Side bending While lying down, crawl your fingers down the side of your thigh. Hold in this tilted position for 5 seconds. Return to a neutral position. Repeat on the other side. Initially, these exercises should be performed while lying down or floating in the bath or hot tub. With improvement, these exercises can be performed standing or sitting. Follow these movements with exercises to strengthen the back. Figure 31-16 Back-stretching exercises. (Redrawn from Anderson BC. Office Orthopedics for Primary Care: Diagnosis and Treatment, 2nd ed. Philadelphia, Saunders, 1999, p 266.)

are effective modalities. NSAIDs or acetaminophen can be reinitiated. The need for prolonged narcotic therapy should prompt reevaluation of a patient’s back pain. Reassurance and psychological support are also important. Often, depression accompanies the pain; addressing psychological issues may provide some relief. Patients often require referral to a specialized pain clinic or multidisciplinary back program. These clinics offer education, physical therapy, pharmacologic treatment, epidural steroid injections, chiropractic therapy, and psychological services. Family physicians should emphasize the prevention of reinjury, review healthy lifestyle changes, and address weight loss, if indicated, as well as continue primary care for the patient.

KEY TREATMENT Acetaminophen and NSAIDs are effective for pain relief in patients with acute low back pain; muscle relaxants are effective for short-term relief (Harwood and Chang, 2002) (SOR: A). Remaining active speeds recovery from low back pain compared with short-term bed rest (Harwood and Chang, 2002) (SOR: A). For chronic low back pain, exercise is more effective than treatment with medication plus return to usual activity. Exercise is as effective as conventional physiotherapy (Carter and Lord, 2002) (SOR: A).

Lumbar Disk Syndromes Key Points • Degeneration of the intervertebral disk can result in herniation, particularly at the L4-L5 and L5-S1 levels. • The presence of pain, radiculopathy, and other symptoms depends on the site and degree of herniation. • Initial screening for pathology and monitoring for complications (progressive neurologic defects, cauda equina syndrome, refractory pain) are essential in managing lumbar disk herniation. • Most patients with herniated disk recover in 4 weeks.

The pattern of lumbar disk herniation is similar to that observed in the cervical spine. The most common levels for a herniated disk are L4-L5 and L5-S1. With aging and repetitive trauma, the disk undergoes significant changes in volume, shape, biochemical composition, and biomechanical properties. Lumbar disk herniations are believed to result from annular degeneration that leads to a weakening of the annulus fibrosus, leaving the disk susceptible to annular fissuring and tearing and subsequently allowing degenerated disk contents to herniate and impinge on adjacent structures (Fig. 31-19). Herniation usually occurs at the weakest area, 641

31


A

B

or impotence, causing the cauda equine syndrome. Often the difficult aspect of evaluating patients with symptoms of a herniated disk is differentiation from low back strain. Pain caused by low back strain is exacerbated with standing or twisting motions, whereas pain caused by disk herniation, especially central, worsens with sitting or bending, Valsalva maneuver, coughing, or sneezing because of increased pressure on annular fibers. A complete physical and neurologic examination can reveal defects at specific levels. The physician first assesses for any external manifestations of pain by inspecting body position, gait, and ROM. The patient may be bending laterally or listing away from the affected side, or may stand with the affected hip and knee slightly flexed to relieve the pain or nerve compression. Local guarding and muscle tenderness on palpation of the area may be present. Sensory examination may reveal deficits along the specific nerve root distribution (Fig. 31-21). Motor weakness should be tested to localize the nerve root. Nerve tension tests (straight-leg raising, crossed straight-leg raising, Lasegue’s test, bowstring sign) are often positive.

Diagnostic Testing

C

D

Figure 31-17 General postural instructions. A, Bend the knees and hips and keep the back straight when lifting. B, Hold objects close to the body when carrying. C, Place one foot on a stool when standing. D, Keep the knees higher than the hips when sitting, and keep the back straight when standing by tucking in the abdomen and tightening the buttocks to decrease swayback. In addition, patients should avoid high-heeled shoes and sleeping on the abdomen, activities that increase lordosis. (Redrawn from Mercier L. Practical

The major finding on plain radiographs of patients with a herniated disk is decreased disk height. Radiographs have limited diagnostic value for herniated disk because degenerative changes are age related and equally present in asymptomatic and symptomatic persons. Therefore, patients with characteristic herniated disk or chronic disk degeneration usually do not require advanced imaging; it should be performed if suspicion is high for cauda equine syndrome, tumor, infection, progressive neurologic symptoms, trauma, or symptoms inconsistent with monoradiculopathy. CT and MRI should also be reserved for patients who fail conservative management and are being considered for surgery. With herniated disk, waiting 4 to 6 weeks is considered advantageous because herniations tend to reduce and most symptoms resolve. Both CT and MRI can identify disk herniations, but CT with myelography has increased sensitivity and specificity. CT also is less expensive and less sensitive to patient movement. However, MRI better visualizes the spinal chord (Fig. 31-22).

Orthopedics, 5th ed. St Louis, Mosby, 2000, p 125.)

Treatment the posterolateral aspect of the disk (Fig. 31-20). Disk herniation is most common in the third and fourth decades of life.

Clinical Features The onset of symptoms is usually gradual; the most common complaint is low back pain. When the disk herniates, it impinges on adjacent structures, causing sharp, burning, stabbing pain radiating down the posterior or lateral aspect of the leg, to below the knee, and finally to the foot. Pain is generally superficial and localized, often associated with numbness or tingling along the dermatome. In more advanced cases, motor deficit, diminished reflexes, or weakness may occur. An occasional massive central herniated disk compresses the cauda equina, resulting in bilateral symptoms, weakness, numbness, difficult urination, incontinence, 642

Although low back pain and radiculopathy are common causes of disability, most patients experience resolution of their symptoms. Family physician is responsible to determine the goals and optimal management for each patient. The condition should be thoroughly explained to the patient, including the likely natural history and the potential forms of treatment. First-line treatment of a patient with lumbar disk syndrome or herniation is conservative, with limited bed rest, adequate pharmacologic treatment, and exercise. Patients are advised to remain active to speed recovery; excessive bed rest can result in deconditioning, bone mineral loss, and economic losses. Pain should be treated with NSAIDs or narcotics, muscle relaxants, and moist heat; most patients begin to improve with this regimen. The patient should resume early ambulation and begin gentle stretching exercises (see Fig. 31-16).

Back: Cervical and Thoracolumbar Spine Before starting a strengthening program for the back, flexibility must be restored with 3 to 6 weeks of daily back stretching. Strengthening exercises should be performed when the body is well-rested. First, the back muscles are stretched out for 5 to 10 minutes. Then sets of 15 to 20 of the following are performed daily for 6 weeks. As the strength of the back increases, the frequency can be reduced to three times a week. Modified sit-ups The knees are kept bent. The lower back is kept flush with the ground. The hands can be kept either behind the neck or held over the chest. The head and neck are raised 3 to 4” and held for 5 seconds. The abdominal muscles will gradually strengthen.

Weighted side-bends In a standing position, a 5- to 15-pound weight is held in the hand. The back is tilted to the weighted side and is immediately brought back to center. The back should be tilted only a few inches! The farther away from the body the weight is held, the greater is the amount of muscle work! After a set of 15 to 20, the weight is shifted to the opposite side.

These specific exercises are complementary to a regular aerobic exercise program. No single exercise is better than another. If you are having problems doing any specific exercise, discuss it with your health care provider. Figure 31-18 Back-strengthening exercises. (Redrawn from Anderson BC. Office Orthopedics for Primary Care: Diagnosis and Treatment, 2nd ed. Philadelphia, Saunders, 1999, p 268.)

Nucleus pulposus

Annulus fibrosus

Annulus fibrosus Nucleus pulposus Figure 31-19 Normal intervertebral disk seen in sagittal section (left) and in horizontal section (right). (Redrawn from Adam JC, Hamblen DL. Outline of Orthopedics, 13th ed. New York, Churchill Livingstone, 2001, p 199.)

Caudal or epidural steroid injection is controversial. Patients who continue to improve should begin preventive therapy, including overall muscle toning such as swimming or water aerobics; specific toning of the muscles of the back should become part of the patient’s daily routine. Lifestyle changes should be incorporated to reduce predisposing factors. Most patients’ disk problem may be effectively treated conservatively; those who do not respond to conservative

t reatment or have persistent symptoms are referred to specialists. Indications for referral include cauda equina syndrome, progressive and profound neurologic deficit, and disabling pain refractory to 4 to 6 weeks of conservative treatment. Any surgical decisions should be firmly based on the clinical symptoms, which are confirmed with results of diagnostic testing. Percutaneous lumbar diskectomy, performed under local anesthesia, is a safe and effective noninvasive alternative to laminectomy. The percutaneous procedure is contraindicated in the presence of tumor, infection, foramina stenosis, loose disk fragments, spondylolisthesis, or severe facet joint arthritis. No long-term difference has been observed in the outcomes of patients treated conservatively versus surgically.

KEY TREATMENT Conservative management is the initial approach in patients with low back pain with radicular symptoms, unless cauda equine syndrome is diagnosed (Snyder et al., 2004) (SOR: C). Procedures for spinal decompression may be considered in patients who have failed conservative therapy (Cochrane Review, 2005) (SOR: C).

643

31


Cauda equina Issuing nerve

A

B

C

Figure 31-20 Stages in prolapse of an intervertebral disk. A, Annulus fibrosus is torn, but no extrusion of nucleus pulposus. B, Extrusion of nuclear material through the rent. Posterior longitudinal ligament is stretched, but protrusion has not reached the nerve. C, The protraction is larger, and the nerve is stretched over it. Sometimes, a fragment of the torn annulus itself protrudes backward. (Redrawn from Adam JC, Hamblen DL. Outline of Orthopedics, 13th ed. New York, Churchill Livingstone, 2001, p 199.)

S1, 2

L1 S3 L2

L4, 5

L2

L5, S1

L2, 3

S2 L3

L3, 4

L5 L4, 5 L4

L5

S1 L5, S1

L4

S1

Figure 31-21 Root (segmental) distribution. Note that motion in each joint is controlled by four nerve roots running in sequence. Hip—flexion L2, L3, extension, L4, L5; knee—extension (and knee jerk) L3, L4, flexion L5, S1; ankle—dorsiflexion L4, L5, plantar flexion (and ankle jerk) S1, S2. (Inversion involves L4, and eversion L5, S1.) A useful mnemonic for the low limb dermatomes is that “we kneel on L3, stand on S1, and sit on S3.” (Redrawn from McRae R, Kinninman AWG. Orthopedics and Trauma. New York, Churchill Livingstone, 1997, p 26).

Thoracolumbar Vertebral Compression Fractures Key Points • Vertebral compression fractures are common, especially in the elderly. Causing significant disability, deconditioning, and pain. • The most common site for fractures is thoracolumbar junction (T12-L1). • Family physicians can prevent compression fractures and sequelae by identifying high-risk patients, educating patients, and encouraging lifestyle modification.

Figure 31-22 MR scan showing inflammatory changes in the L3-L4 disk (diskitis) and an L4-L5 prolapse. (From McRae R, Kinninman AWG. Orthopedics and Trauma. New York, Churchill Livingstone, 1997, p 52.)

644

Vertebral compression fractures are common, especially in elderly persons. Vertebral fractures can cause significant pain and impairment in activities of daily living, leading to potentially life-threatening disability and deconditioning in the elderly patient. Patients with preexisting vertebral fractures have greater risk of future vertebral as well as nonvertebral (especially hip) fractures than those without prior fractures.


The most common site for fractures is the thoracolumbar junction (T12-L1) because the change in facet provides poor resistance to anteroposterior displacement. The other common location is the midthoracic region (T7-T8). Osteoporosis is the most frequent cause of vertebral compression fractures in the elderly population. Other causes should be suspected if fracture occurs in a person neither elderly nor postmenopausal or if solitary fracture higher than T7 is seen, ruling out osteomalacia, hyperparathyroidism, granulomatous disease, and hematologic disease.

Clinical Features Most thoracolumbar compression fractures are asymptomatic, diagnosed as incidental findings on chest or abdominal plain radiographs. Patients with symptomatic fractures usually have no preceding history of trauma, and even minimal trauma (coughing, sneezing) can cause the fracture. The pain from a vertebral compression fracture is variable in quality and sharp or dull. Movements aggravate the pain. The classic patient presents with acute back pain radiating to the anterior abdomen, unlike radiation into the legs seen in herniated disk. Physical examination may reveal tenderness directly over the area of fracture. Thoracic kyphosis and lumbar lordosis may be noted secondary to vertebral height lost. Straight-leg raise and neurologic exam are normal in uncomplicated fractures. Acute episodes usually resolve after 4 to 6 weeks; if pain lasts longer, the physician should suspect more fractures, with chronic pain or other diagnosis.

Diagnostic Testing A complete blood count, erythrocyte sedimentation rate, and alkaline phosphatase, serum calcium, phosphorus, vitamin D, and parathormone levels should be obtained to rule out malignancy, hyperparathyroidism, or infection, if a cause other than osteoporosis is suspected. Plain radiographs are obtained if compression fracture is suspected. Radiographic characteristics of compression fractures include anterior wedging of one or more vertebrae, with vertebral collapse, demineralization, and vertebral end-plate irregularity. Advanced imaging is not routinely necessary unless the patient has a neurologic abnormality, which may indicate fracture fragments in the spinal canal. Imaging also helps rule out other causes of back pain.

Treatment Initial management involves pain control and resumption of exercise as early as possible. When osteoporosis is present, inactivity could lead to further bone loss and subsequent fractures. Nonnarcotic analgesics should be used for pain relief. If narcotics are required, laxatives should be used because straining with defecation can cause further fractures. Nasal calcitonin may be a useful adjunct to these analgesics for acute pain relief. Treating the underlying disease is important. Muscle relaxants, external back braces, and physical therapy also may help. Immediate surgical referral should be made if fracture fragments are impinging on the chord and causing neurologic symptoms, or if the fracture is unstable.

Most patients respond to conservative treatment, with significant improvements or full recovery after 6 to 12 weeks. Patients who do not respond to conservative treatment may be candidates for percutaneous vertebroplasty or kyphoplasty. The family physician can help patients prevent compression fractures and the sequelae by identifying high-risk patients, educating patients about measures to prevent falls, and encouraging lifestyle modifications. A regular weightbearing exercise program, adequate calcium and vitamin D supplement intake, smoking cessation, and medications to treat osteoporosis may help prevent additional compression fractures.

KEY TREATMENT Conservative management (pain management, back braces, physical therapy) is the first line of therapy for stable compression fractures (Old and Calvert, 2004) (SOR: B). Patients nonresponsive to conservative treatment may be candidates for percutaneous vertebroplasty or kyphoplasty (Predley et al., 2002) (SOR: B). Diagnosing and treating osteoporosis reduces the incidence of compression fractures of the spine (Old and Calvert, 2004) (SOR: A). Regular activity and muscle-strengthening exercises have been shown to decrease vertebral fractures and back pain (Sinaki et al., 2002) (SOR: B).

Spinal Stenosis Spinal stenosis is the narrowing of the spinal canal and neural foramina. Spinal stenosis has been classified into congenital and acquired types. The more common acquired spinal stenosis is caused by degenerative changes in the intervertebral disks, ligaments, and facet joints surrounding the lumbar canal. These degenerative changes can be caused by disk or joint disease, back surgery, and repetitive trauma. Stenosis initially becomes symptomatic at 40 to 50 years and older. Congenital narrowing of the spinal canal causes symptoms earlier in life and is uncommon. Spinal stenosis usually occurs at cervical and lumbar segments. Patients with cervical stenosis present with radiating arm pain, numbness, paresthesia, and motor weakness. The common symptoms with lumbar stenosis are insidious low back pain, leg pain, and numbness. The pain is most often bilateral, involving the buttocks and thighs and spreading distally toward the feet. The classic presentation is radiating leg pain (burning or cramping) that begins or worsens with walking and standing and is relieved by sitting or lying down with hips and knees drawn up in a sitting posture (neurogenic claudication). Bending forward diminishes pain. The signs and symptoms of neurogenic claudication should be differentiated from the leg claudication produced by vascular claudication. Vascular disease pain is exercise induced, is localized to the affected group of muscles, and is relieved rapidly with rest in any position. Neurologic symptoms are absent, and vascular disease is associated with skin and trophic changes (pallor, cyanosis, nail dystrophy, decreased or absent pulse). Severity of symptoms in spinal stenosis may not necessarily be associated with the degree of compression seen on imaging studies. Rarely, patients with spinal stenosis present with 645

31


A

B

Figure 31-23 Normal (A) and abnormal (B) CT scans of the lumbar spine. Marked narrowing (arrow) is present in B because of hypertrophic spurring. (From Mercier R. Practical Orthopedics, 5th ed. St Louis, Mosby, 2000, p 129.)

signs or symptoms of muscle atrophy and loss of bowel and bladder control. Physical examination is frequently normal but may include loss of lumbar lordosis, impairment of spinal mobility, asymmetric knee or ankle reflexes, and muscle weakness. Results of straight-leg raising are characteristically negative. Advanced imaging studies are obtained to establish and confirm the diagnosis of spinal stenosis when surgery is considered. Plain spine radiographs often reveal degenerative changes. MRI is currently the preferred modality, followed by CT scan (Fig. 31-23). Conservative treatment is the first line of therapy for spinal stenosis, including adequate pain management, physical therapy, exercise, and weight loss. Progressive symptoms or intractable pain warrant surgical intervention. Wide decompression at the level of stenosis can relieve the symptoms.

KEY TREATMENT Patients with mild to moderate symptoms of spinal stenosis are managed conservatively (pain/physical therapy, exercise, weight loss) (Snyder et al., 2004) (SOR: C). Patients with severe symptoms of spinal stenosis benefit from surgery (Amundsen et al., 2000) (SOR: B).

Scoliosis Scoliosis is characterized by the lateral deviation of the spine from its normal position and is associated with rotation of the vertebrae. Scoliosis may be caused by a structural spine deformity or another problem (e.g., unilateral leg shortening) or may be a protective reaction of muscle spasm in the back for lumbar disk disease or inflammation. Of the structural causes, idiopathic scoliosis is most common, affects women more frequently, and is often asymptomatic in young people. Other causes include neurologic deficit,

646

Figure 31-24 Scoliosis with rib prominence resulting from vertebral rotation is best exhibited on forward bending (Adams position). Cross section of the chest shows rib distortion resulting from vertebral rotation. (Redrawn from Mercier R. Practical Orthopedics, 5th ed. St Louis, Mosby, 2000, p 132.)

myopathy, and neurofibromatosis; presence of pain may signify another cause. The patient with scoliosis may present with apparent deformity, pain, symptoms of difficult movement, or neurologic deficits. The examiner stands behind and observes the patient bending forward at the waist with arms loosely directed toward the feet, which may reveal a prominence of the ribs on one side of the back of the chest and abnormal curvature of the spine (Fig. 31-24). Worsening scoliosis may result in pain, progressive deformity, disability, and cardiopulmonary compromise. Radiographs aid in the diagnosis and also allow measurement of the angle of curvature of the spine (Fig. 31-25). MRI may be indicated if there are additional symptoms, such as pain or neurologic problems. Early detection is important, and prompt referral to specialists is indicated in certain cases. Spinal growth continues until bone growth has been completed, and serial radiographs are useful to monitor the condition. Treatment of scoliosis is primarily based on severity and angle of curvature. Braces may be recommended and in special cases, surgery (Janicki and Alman, 2007; SOR C, 3).


b a

Figure 31-25 Cobb method of measuring the severity of a curve. Upper and lower end vertebrae are identified. Upper end vertebra is higher, its superior border converging toward the concavity of the curve, and lower end vertebra has inferior border converging toward the concavity. Lines are drawn along these borders, and the curve is measured directly (a) or geometrically (b). (Redrawn from Mercier R. Practical Orthopedics, 5th ed. St Louis, Mosby, 2000, p 132.)


Web Resources www.ninds.nih.gov/disorders/backpain/backpain.html Information on back pain with links to other sites, including clinical trials in the U.S. and worldwide. www.aaos.org/research/research.asp American Academy of Orthopedic Surgeons site that includes Clinical Practice Guidelines, Research News, and information about common musculoskeletal disorders.

www.nlm.nih.gov/medlineplus/neckinjuriesanddisorders.html www.familydoctor.org Consumer health information on a variety of disorders, provided by the American Academy of Family Physicians.

647

32 CHAP T E R Rheumatology and Musculoskeletal Problems Douglas Comeau, Kevin Heaton, and Andrea Gordon

Chapter contents Evaluation of Joint and Other Musculoskeletal Symptoms Physical Examination

648 650

Pathogenesis of Rheumatic and Other Musculoskeletal Diseases

650

Laboratory Studies

652

Synovial Fluid Analysis Imaging Studies Functional Assessment Arthritis of Systemic Disease Referral to the Rheumatologist

652 653 653 654 655

Rheumatic Diseases

655

Osteoarthritis Rheumatoid Arthritis Crystal Arthropathies Spondyloarthropathies

655 659 668 672

Arthritis is the most common health complaint in the United States and a common reason for an office visit to the family physician, despite the numerous over-the-counter treatments for joint pain and other musculoskeletal problems. In a Center for Disease Control and Prevention (CDC) National Ambulatory Medical Care Survey, 49 million American adults reported physician-diagnosed arthritis, 21 million of whom reported chronic joint symptoms (Hootman and Helmick, 2006). The 30-year projection rate of patients age 65 and older will increase from 21.4 million to 41.4 million. These statistics lead to 75,000 hospitalizations and 36 million outpatient visits annually. The term arthritis actually applies to more than 180 different disorders, all with pain in or around one or more joints, some with an inflammatory component. Although patients and physicians refer to this collection of diseases as arthritis or “rheumatism,” the family physician must attempt to identify the disease process more precisely because of the many treatments available. Musculoskeletal symptoms might be harbingers of other, serious diseases affecting other organs. Patients should know their prognosis, whether their symptoms will most likely be self-limited, chronic, or progressive. Rheumatic diseases greatly impact the U.S. health care system and society. Approximately 1% of the U.S. gross national product is spent each year on rheumatic diseases alone. Work absences, lost wages, and long-term disability also impact the quality of life of patient and family. Family physicians must be knowledgeable about new treatment ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10020-8

Infectious Arthritis Rheumatic Fever Systemic Lupus Erythematosus Sjögren’s Syndrome Vasculitic Syndromes Fibromyalgia Syndrome Temporomandibular Joint Syndrome

675 677 678 681 682 685 687

Rheumatic Disease in Children

687

Juvenile Rheumatoid Arthritis Spondyloarthropathies Systemic Lupus Erythematosus in Childhood Henoch-Schönlein Purpura Kawasaki’s Syndrome Nonarticular Rheumatism

Rheumatology Information on the Internet

687 687 687 688 688 688

688

options in the evaluation, assessment, and treatment of these conditions.

Evaluation of Joint and Other Musculoskeletal Symptoms Precise anatomic localization of pain is the first task of the physician caring for a patient presenting with joint pain, while also evaluating stiffness, redness, warmth, or swelling in the absence of trauma. It is important to distinguish pain that is truly articular from periarticular pain. Causes of localized periarticular pain include bursitis, tendonitis, and carpal tunnel syndrome, whereas fibromyalgia, polymyalgia rheumatica, and polymyositis all can cause diffuse periarticular pain. The number of involved joints and presence or absence of symmetry are criteria for further diagnosis of articular pain (Figs. 32-1 and 32-2). Monoarticular (one joint) or oligoarticular (several joints) arthritides can be caused by conditions such as osteoarthritis (OA), gout, pseudogout, or septic arthritis. Asymmetric polyarthritis occurs in ankylosing spondylitis, psoriatic arthritis, Reiter’s disease, and spondyloarthropathies. Symmetric arthritis, meaning that the same joint is affected on the contralateral side but not necessarily to the same degree, is characteristic of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren’s syndrome, polymyositis, and scleroderma. Fibromyalgia, reflex sympathetic dystrophy, and predominantly psychological

Rheumatology and Musculoskeletal Problems

Arthralgia limited to one or several joints

Complete history and physical examination

Significant trauma or focal bone pain

X-ray

(+)

Abnormal

FRACTURE, TUMOR, or METABOLIC BONE DISEASE

(–)

(+) Probable inflammatory process

Unsuccessful

Re-evaluate

Bloody

COAGULOPATHY, PSEUDOGOUT, TUMOR, TRAUMA, or CHARCOT’S JOINT Check: PT/PTT Platelet count Bleeding time

Effusion or signs of inflammation?

Normal

(–)

Joint aspiration

Point tenderness or trigger points

(+)

BURSITIS TENDINITIS, or FIBROMYALGIA

Successful (–)

Bone marrow elements present

>2000 WBCs? >75% PMNs?

(–)

OSTEOARTHRITIS, INTERNAL DERANGEMENT, SOFT-TISSUE INJURY, or VIRAL INFECTION

(+)

INTRAARTICULAR FRACTURE

Crystals identified

Positive culture*

MONOSODIUM URATE (gout)

INFECTIOUS ARTHRITIS

CALCIUM PYROPHOSPHATE DIHYDRATE (pseudogout)

*Synovial fluid culture as well as cervical, urethral, pharyngeal, and/or rectal evaluations for Gonococcus and Chlamydia when suspected.

Sterile inflammatory joint fluid

Suspect: RA, JRA, VIRAL, SLE, LYME, SARCOIDOSIS, or SPONDYLOARTHROPATHY Check: CBC, ESR, RF Consider: LFTs, HLA-B27, ANA, Lyme serologies, and pelvis radiographs

Figure 32-1 Evaluation of monoarticular or pauciarticular symptoms. ANA, Antinuclear antibodies; CBC, complete blood cell count; ESR, erythrocyte sedimentation rate; JRA, juvenile rheumatoid arthritis; LFTs, liver function tests; PMNs, polymorphonuclear (leukocyte) neutrophils; PT, prothrombin time; PTT, partial thromboplastin time; RA, rheumatoid arthritis; RF, rheumatoid factor; SLE, systemic lupus erythematosus; WBCs, white blood cells. (From American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms. Arthritis Rheum 1996;39:1.)

factors must be considered when pain is diffuse, not relatable to specific anatomic structures, or described in vague terms. (See also Chapter 30.) Other differentiating criteria include the correlation with activity or rest and the character of the pain. Mechanical causes tend to be more directly related to the joint’s activity than inflammatory conditions. Neuropathies tend to cause burning or prickling sensations, whereas arthritides often cause an aching pain. The presence of joint stiffness after a period of inactivity might also aid in diagnosis; RA is characterized by morning stiffness lasting 30 to 60 minutes or

longer, whereas OA-related morning stiffness lasts a shorter period, typically less than 30 minutes, but stiffness might also occur during the day. In neurologic conditions such as Parkinson’s disease, stiffness might be relatively constant. Vascular pain, such as intermittent claudication, is felt with activity, relieved quickly by rest, and described as a “deep, aching” sensation. Constitutional symptoms such as fatigue, weakness, malaise, and weight changes are common chief complaints heard in a primary care office practice and often associated symptoms of specific rheumatic diseases. The patient’s 649

32


f unctional ability, occupational history, and activities requiring repetitive joint movement, as well as the ergonomics of such activities, should also be considered routinely in initial and serial evaluations. How are the symptoms affecting the patient’s ability to perform self-care activities of daily living (ADLs) such as bathing, dressing, and eating? Is the patient able to do instrumental activities of daily living (IADLs) such as buying groceries, cooking, using the telephone, and opening jars? Rheumatic disease can have a devastating effect on quality of life for both the patient and the family, with serious psychosocial and economic consequences. Therefore the physician should address effects on occupational, recreational, and sexual activities in the context of family and other support systems.

recording the maximal grip force in millimeters of mercury. Signs of systemic disease include fever; weight loss; oral or nasal ulcerations; liver, spleen, or lymph node enlargement; neurologic abnormalities; rashes; subcutaneous nodules; eye iritis; conjunctivitis or scleritis; and pericardial or pulmonary rubs. Because of circadian changes in patients with RA, serial comparisons of the physical examination are more accurate if the time of day is also recorded. Using skeleton diagrams of joint involvement facilitates the recording of a comprehensive joint examination (Fig. 32-3). Myalgias can be caused by localized trauma or overuse, systemic infection, metabolic disorder, or primary muscle disease. Multiple tender sites in an otherwise healthy patient suggest fibromyalgia. An elevated creatine kinase (CK) level with proximal weakness may be caused by an inflammatory myopathy. Rheumatic and other musculoskeletal problems are properly diagnosed by careful history and physical examination rather than by just ordering many laboratory tests, the results of which might actually confuse diagnosis. Laboratory tests and radiologic imaging help confirm a presumptive clinical diagnosis made from a careful history and physical examination.

Physical Examination A thorough physical examination should be performed on all patients presenting with joint pain, including examination of asymptomatic joints and other organ systems that might be involved. Joints should be examined for swelling, tenderness, deformity, instability, and limitation of motion. Comparisons with the patient’s contralateral side can be made in all these parameters, as well as with the physician’s joints as a control. Instability can be tested by moving adjacent bones in the direction opposite to normal movement and observing for greater-than-normal motion. Serial grip strength measurements can be made by asking the patient to squeeze a blood pressure (BP) cuff inflated to 20 mm Hg and

Pathogenesis of Rheumatic and Other Musculoskeletal Diseases As with most disease, research into the causes of rheumatologic and musculoskeletal diseases shows that the cause for each disease is actually multifactorial. Further identification

Polyarthralgia

Complete history and physical examination (–)

Synovitis?

Tender points?

(+)

(+)

FIBROMYALGIA or MULTIPLE SITES OF BURSITIS or TENDINITIS

Symptoms > 6 weeks (–) (+) SYSTEMIC RHEUMATIC DISEASE

(–) VIRAL ARTHRITIS EARLY SYSTEMIC RHEUMATIC DISEASE

Careful follow-up

Check: CBC, ESR, RF, and/or ANA; creatinine, urinalysis, joint aspiration (if effusion present; see Fig. 40-1 for analysis).

Check: Blood count Liver function tests Consider: Hepatitis B and C serology Parvovirus serology

VIRAL ARTHRALGIA OSTEOARTHRITIS SOFT-TISSUE ABNORMALITIES HYPOTHYROIDISM NEUROPATHIC PAIN METABOLIC BONE DISEASE DEPRESSION

Consider: Liver function tests Hepatitis B and C serology Radiographs Thyroid-stimulating hormone Calcium Albumin Alkaline phosphatase

Figure 32-2 Evaluation of polyarticular symptoms. ANA, Antinuclear antibodies; CBC, complete blood cell count; ESR, erythrocyte sedimentation rate; RF, rheumatoid factor. (From American College of Rheumatology Ad Hoc Committee on Clinical Guidelines: Guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms. Arthritis Rheum 1996;39:1.)

650


of these factors will help the family physician and rheumatologist modify the course of disease and eventually perhaps even prevent them. Genetic factors have been identified for several arthritides. Presence of the human leukocyte antigen (HLA) system’s HLA-DR4 antigen is associated with increased incidence and severity of RA. The HLA-B27 antigen is found in a higher percentage in patients with ankylosing spondylitis and other spondyloarthropathies than in the general population. Other factors are apparently involved,

Figure 32-3 Skeleton diagram for recording joint examination findings. (From Polley HF, Hunder GG. Rheumatologic Interviewing and Physical Examination of the Joints, 2nd ed. Philadelphia, Saunders, 1978.)

owever, because its presence or absence neither guaranh tees nor excludes development of arthritis testing for these antigens if not routinely performed. A National Institutes of Health (NIH) study found that genetic factors contributed 39% to 65% of OA variance. About 80% of patients with chondrodysplasias were found to have a type II collagen gene mutation likely linking these findings to OA (Prockop, 1998). Inborn errors of metabolism are well known to cause diseases such as gout, in which uric acid is overproduced or underexcreted by the kidneys. Poorly controlled metabolic diseases such as diabetes or hemochromatosis might lead to arthropathies. Mechanical or traumatic factors cause OA in soccer players but not in long-distance runners, indicating that the type and direction of joint stress might be more important than the stress itself. Adduction moment is associated with OA disease severity. Obesity is also an identified factor in OA of the knee, possibly because of metabolic influences as well as mechanical forces (Eaton, 2004). Infectious agents such as parvovirus B19, human immunodeficiency virus (HIV), Neisseria gonorrhoeae, Borrelia burgdorferi (Lyme disease), and streptococci (rheumatic fever) are all well-known causes of arthritides. Some speculate that dietary factors might contribute to autoimmune syndromes, and fasting or a vegan diet (or both) can lead to improvement in RA (Kjeldsen-Kragh et al., 1991; McDougall et al., 2002). The imbalance of omega-6 and omega-3 fatty acids in the standard American diet (a ratio of 30:1, as opposed to the ratio of 1:2 that is thought to have been present in Paleolithic diets) is also postulated to contribute to a more inflammatory state. Omega-6 fatty acids are preferentially converted to more inflammatory prostaglandins such as arachidonic acid, whereas omega-3 fatty acids can be converted into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which contribute to anti-inflammatory series-3 prostaglandin production (Fig. 32-4). Omega-3 fatty acids are useful in RA, showing a decrease in use of nonsteroidal antiinflammatory drugs (NSAIDs) and decreased levels of pain (Oh, 2005).

Omega 6 fatty acid (linoleic acid)

Omega 3 fatty acid (alpha linoleic acid) ∆6-Desaturase

Gamma linolenic acid (GLA) Evening primrose oil Borage oil Black currant oil ∆5-Desaturase Arachidonic acid Cyclooxygenase (COX) Lipoxygenase Prostaglandins (PGE2) Inflammatory

Eicosapentaentaenoic acid (EPA)

COX Prostaglandins PGE1 PGE3 (favorable)

Lipoxygenase Less inflammatory leukotrienes

Leukotrienes Docosahexaenoic acid (DHA)

Figure 32-4 Influence of omega-6 fatty acids and omega-3 fatty acids on inflammation. (From Rakel R. Integrative Medicine. Philadelphia, Saunders-Elsevier, 2007.)

651

32


Other medical systems, such as traditional Chinese medicine (TCM), may have completely different explanations for the changes seen in rheumatologic conditions. Although a conventional practitioner may not be aware of these, it is helpful to know about complementary modalities that may be beneficial (e.g., acupuncture helping patients with OA and fibromyalgia).

Laboratory Studies A complete cell count (CBC) with differential, urinalysis, and renal and liver function tests should be performed if asymptomatic rheumatic disease is suspected. Importantly, the frequency of abnormal laboratory results increases with increasing age in the normal population, even in the absence of disease, including common tests such as erythrocyte sedimentation rate (ESR), uric acid, antinuclear antibodies (ANAs), and rheumatoid factor (RF). Thus, arthritis panels can confuse the situation and should not be performed routinely. For example, only 80% of patients with RA have a positive RF. RF is a serum autoantibody against immunoglobulin G (IgG). Up to 4% of the healthy population has a positive RF, which is also frequently positive in patients with chronic obstructive pulmonary disease (COPD), viral hepatitis, and sarcoidosis, and can also be positive in malignancy, and primary biliary cirrhosis and other autoimmune diseases. The higher the RF titer, however, the more likely it is caused by RA. ANA test results are positive in 95% of patients with lupus, and the test is often used to screen for SLE, but the result is also positive in 5% of the normal population. Drug use, age, and other factors might also cause a positive ANA test result. ANA titer also does not correlate exactly with changes in disease activity, so it should not be ordered in the absence of systemic symptoms. A patient with a positive ANA without clinical features is unlikely to have SLE. However, higher titers of ANA make it more likely that the result is related to lupus or another rheumatologic disorder. Laboratory studies can be helpful in monitoring disease activity and drug toxicity as well as in establishing a diagnosis. CBC can detect anemia secondary to the chronic disease of RA or from NSAID-induced gastrointestinal (GI) blood loss. Patients with SLE can have hemolytic anemia, thrombocytopenia, or lymphopenia. Urinalysis can detect renal disease secondary to SLE, NSAIDs, or disease-modifying antirheumatic drugs (DMARDs) being used to treat RA. An elevated uric acid level can suggest gout. Acute-phase reactants such as ESR and C-reactive protein (CRP) can be useful to monitor disease activity but are nonspecific; they can also be negative in the presence of active disease. Patients with temporal arteritis and polymyalgia rheumatica almost always have a greatly elevated ESR. With weakness or muscle pain, CK level should be measured and arthralgias with abnormal liver enzyme levels followed up with hepatitis viral serologies. Other tests, such as HLA-B27, antineutrophil cytoplasmic antibody, Lyme or parvovirus serologies, myositis-specific antibodies (anti–Jo-1), and antiphospholipid antibodies, are useful only when the clinical suspicion is high for spondyloarthropathies, Wegener’s granulomatosis, Lyme or parvovirus infection, inflammatory myositis, or antiphospholipid 652

Table 32-1 Interpretation of Synovial Fluid Cell Count

Leukocyte Count (WBCs/mm3)

Interpretation

100,000

Sepsis, until proved otherwise

From Towheed TE, Hochberg MC. Acute monoarthritis: a practical approach to assessment and treatment. Am Fam Physician 1996;54:2239. WBCs, White blood cells; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis.

antibody syndrome, respectively (American College of Rheumatology, 1996).

Synovial Fluid Analysis Synovial fluid analysis can be helpful in evaluating a febrile patient with an acute joint to rule out septic arthritis or acute monoarthritis. Synovial fluid should be analyzed for white blood cell (WBC) count differential, cultured, and tested with polarized light microscopy for crystals. Purulent synovial fluid with greater than 90% polymorphonuclear leukocytes (PMNs), low viscosity, and turbid clarity can be caused by infection or crystal arthropathy (gout or pseudogout). Urate crystals are needle-shaped and negatively birefringent; calcium pyrophosphate dihydrate crystals are rhomboidal and weakly positively birefringent. Noninflammatory fluids generally have a clear appearance, normal viscosity, fewer than 2000 WBCs/mm3, and less than 75% PMNs (Table 32-1). Synovial fluid analysis should always be performed on freshly obtained fluid. A simple bedside test is to attempt to read newsprint through the synovial fluid; newsprint can be read through noninflammatory fluid (Fig. 32-5). Traditional tests on synovial fluid that are of limited or no value include measurement of glucose, lactate, and protein levels; subjective determination of viscosity; mucin clot test (examining the friability of the precipitate formed by mixing synovial fluid with dilute acetic acid); and immunologic tests. When looking for crystals and infection, direct examination, Gram stain, culture, and WBC count with differential are the only tests worth performing on synovial fluid. Inflammatory synovial fluid must be considered secondary to infection until proved otherwise by culture. The presence of crystals in the joint does not exclude the possibility of joint infection. Synovial biopsy can facilitate a diagnosis in some settings. Arthroscopy has greatly simplified the acquisition of synovial tissue. This might be helpful in the diagnosis of granulomatous disease or infiltrative processes such as lymphoma, metastatic disease, or amyloidosis (Klippel, 2001).


Figure 32-5 Synovial effusions. A, Normal or edema fluid is clear, pale yellow, or colorless. Print is easily read through the tube. B, Fluid from noninflammatory joint disease is yellow and clear. C, An inflammatory effusion is cloudy and yellow. Print may be blurred or completely obliterated, depending on the number of leukocytes. The effusion is translucent. D, A purulent effusion from septic arthritis contains a dense clump that does not even allow light through the many leukocytes. E, Hemorrhagic fluid is red. The supernatant may be darker yellow-brown (xanthochromic). A traumatic tap is less uniform and often has blood streaks. (From Schumacher HR. Synovial fluid analysis and synovial biopsy. In Kelley WN, Harris ED, Ruddy S, et al [eds]. Textbook of Rheumatology, 5th ed, vol 1. Philadelphia, Saunders, 1997, pp 609-625.)

Imaging Studies

Functional Assessment

Plain radiographs are still the most common imaging studies done for evaluation and management of rheumatic diseases. Techniques such as magnetic resonance imaging (MRI) and radionuclide scintigraphy (bone scan) are being used more often, although costly and often unnecessary. Many arthritides have characteristic radiographic findings, but these techniques are not indicated for most patients with acute and new symptoms of SLE, gout, mechanical lower back pain, or RA, because radiographs are usually normal early in the course of the disease. Normal radiographs also do not rule out OA. In established RA, the physician might see periarticular osteoporosis, soft tissue swelling, and marginal erosions. Gouty erosions cause characteristic overhanging edges because of reparative changes. (See also Chapter 31.) The severity of radiographic changes in association with severe symptoms can help guide the aggressiveness of treatment. Overreliance on radiographs, however, can lead to undertreatment or overtreatment of disease. Treatment of RA with a DMARD should usually be initiated long before severe radiographic abnormalities are present. The near-ubiquitous presence of osteophytes on the lumbar vertebrae should not be used to justify aggressive surgical treatment for low back pain; on the other hand, many patients with chronic lower back pain have normal lumbar radiographs. Radiographs for acute joint symptoms might be helpful to rule out fractures, metastases, or infection, especially in older patients. If symptoms persist for more than 10 days, the physician should consider repeat radiography, looking for callus formation. Besides rotator cuff injuries, MRI studies are particularly useful for possible cruciate ligament, complete lateral collateral ligament (LCL), and meniscal tears in the knee for potential surgical candidates. Although expensive, MRI shows soft tissue destruction long before plain radiographs. Bone scans also are costly and are nonspecific but demonstrate RA changes before radiographs.

Instruments such as the Arthritis Impact Measurement Scale and the Health Assessment Questionnaire Disability Index can quantify the impact of the rheumatic disease process on quality of life, pain, physical function, and psychosocial adaptation. However, these tools are more useful in clinical research studies than a busy family physician’s office practice. A functional assessment screen is a practical tool for the family physician and takes only minutes (see eTable 32-1 online). Focusing on disease impact on the patient as well as on the patient’s joints can be an important contribution by the family physician. Functional assessment helps the primary care physician determine the role of other team physicians (rheumatologist, orthopedic surgeon, physical therapist, occupational therapist, mental health professional). Assessment of function can also lead to a discussion of disease impact on the family and help them deal with this chronic, possibly progressive condition.

Arthrocentesis Arthrocentesis is most helpful in diagnosing crystal-induced and septic arthritis. Synovial fluid analysis can also be helpful in ruling out the coexistence of two or more types of arthritis in a single patient and even in a single joint. RA might coexist with a septic joint, secondary OA, hemarthrosis, or calcium pyrophosphate dihydrate (CPPD) disease. Hemarthrosis and bacterial infections usually occur in joints already damaged by arthritis. Arthrocentesis is a simple office procedure that can rule out bacterial infection in an acutely inflamed joint. Untreated or delayed treatment of infectious arthritis can cause rapid joint destruction, necessitating prompt diagnosis. A second line of treatment for RA should generally not be started until crystal arthropathy first has been ruled out. A physician is much more likely to harm a patient by not obtaining synovial fluid analysis when needed to make an accurate diagnosis. This is more common than the relatively rare occurrence of iatrogenic infection (particularly if proper sterile technique 653

32


is used) or hemarthrosis (usually seen in patients with coagulopathies). The iatrogenic infection rate is generally estimated at 1 in 10,000, much less common than missed diagnosis of a septic joint. Anticoagulation therapy is not an absolute contraindication in the setting of acute arthritis. The preferred route of entry for arthrocentesis traverses the shortest distance through tissue and avoids major vessels, tendons, and nerves. The knee, ankle, wrist, and elbow are the easiest joints to aspirate, and aspiration can be performed with only a moderate amount of trauma. Other joints normally require more extensive experience. Sterile technique normally does not require draping, but the same needle should not be used to aspirate the joint and to transfer the aspirated fluid to collection bottles. The knee is the easiest joint to aspirate, best done with a medial or lateral approach at the superior third of the patella between it and the femur. Ankle arthrocentesis entry is midline, equidistant from the medial and lateral malleoli. A lateral entry between the olecranon process and the lateral epicondyle is best for the elbow. The shoulder can be approached posteriorly below the posterolateral aspect of the acromion process or anteriorly just lateral to the coracoid process. A local anesthetic can be used but might distort landmarks; ethyl chloride spray immediately before needle insertion is usually sufficient. An 18-gauge needle is used for the knee and a 20-gauge needle for other joints; only 1 to 5 mL of synovial fluid is needed for diagnostic purposes. Fluid aspiration by itself is often therapeutic because it reduces articular pressure. Cartilage puncture should be avoided, if possible, by inserting the needle only as deeply as needed to obtain fluid, obtaining as much fluid as possible without risking unnecessary trauma by trying to aspirate every last drop, and avoiding side-to-side needle movement.

Therapeutic Corticosteroid Injection Arthrocentesis can also be a therapeutic technique to deliver local corticosteroid to a joint that has not responded to systemic therapy and after infection has been excluded. Synovial fluid is first aspirated to ensure proper positioning in the joint space, followed by 1 to 2 mL of corticosteroid to large joints (knees, hips, shoulders); 0.5 to 1 mL to wrists, elbows, and ankles; and 0.25 to 0.5 mL to small joints and soft tissue sites. A 1:2 dilution with lidocaine can be used to provide instant relief, although many believe lidocaine adds to the risk of infection (e.g., requiring a more complex procedure, changing needles) with limited benefit and therefore do not use it. After injection, the joint should be moved through its passive range of motion (ROM), followed by at least 24 hours of rest. Steroid injections should be limited to no more than three to four times per joint per year because of concerns about possible cartilage and ligamentous damage from repeated injections.

Nonsteroidal Anti-Inflammatory Drugs The NSAIDs are among the most frequently prescribed drugs and are used by family physicians for almost all rheumatic and musculoskeletal pain conditions. By suppressing the synthesis of prostaglandins, NSAIDs reduce inflammation and therefore pain but do not prevent tissue injury or joint damage. Cyclooxygenase-2 (COX-2) inhibitors are used for rheumatologic and musculoskeletal pain because of decreased GI side effects. The VIGOR (Bombardier et al., 2000) and CLASS (Silverstein et al., 2000) studies 654

for rofecoxib and celecoxib, respectively, showed that the decreased GI effects outweighed any cardiovascular risk. The APPROVe study linked rofecoxib (Vioxx) to an increased risk of cardiovascular disease (Bresalier et al., 2005). An unpublished trial studying celecoxib (Celebrex) and naproxen (Naprosyn, Aleve) in Alzheimer’s disease prevention was stopped secondary to a 50% increase in cardiovascular events in subjects not taking placebo (NIH, 2004). Overall, COX-2 inhibitors have produced minimal decrease in GI bleeding and thus should be used cautiously for rheumatologic and musculoskeletal pain because the cardiovascular risk outweighs the GI benefit. Currently, celecoxib has a “black box” warning; rofecoxib was removed from the market. Patients respond to different classes of NSAIDs for unknown reasons, and no NSAID appears superior to others in efficacy. Treatment is largely empiric. Most clinicians start with a low dose and titrate upward if needed. An adequate trial of an NSAID requires that the patient take a maximum dose for 3 weeks before changing to a different NSAID, although many patients will expect a change in medication before this. It is usually best to switch to an NSAID from a different class. There is no benefit to combining nonsalicylate NSAIDs. All COX-1 NSAIDs can cause dyspepsia and GI toxicity, interfere with platelet function, and prolong bleeding times. Other common side effects include renal toxicity and central nervous system (CNS) symptoms such as drowsiness, dizziness, and confusion. A 2004 Cochrane review of NSAIDs for lower back pain concluded that the various types of NSAIDs (e.g., COX-2 inhibitors) are equally effective, and selection of an NSAID for OA should be based on relative safety and patient acceptability. Combining NSAIDs with misoprostol (Cytotec), 100 to 200 mg four times daily with meals, or omeprazole (Prilosec), 20 mg daily (Hawkey et al., 1998) has been shown to decrease the incidence of gastric and duodenal ulcers. A meta-analysis of 112 randomized controlled trials (RCTs) found no evidence supporting the effectiveness of H2 receptor antagonists, while the risk of symptomatic ulcers was significantly reduced by proton pump inhibitors (PPIs), misoprostol, and COX-2 inhibitors (Koch et al., 1996). Omeprazole and other PPIs are better tolerated than misoprostol and famotidine (Hawkey et al., 1998). The physician should monitor for decreased renal function, interaction with antihypertensives, and transaminase (ALT, AST) elevations when starting NSAID therapy or increasing dosage, or when the patient’s condition changes. A common issue for the family physician is whether a patient prescribed aspirin for cardiac prophylaxis needs to stop the aspirin when prescribed a traditional NSAID. Patients taking both do not appear to be at significantly increased risk of GI toxicity. However, the aspirin might not yield any additional cardioprotective benefit, because these patients already benefit from the traditional nonselective NSAID antiplatelet effect. If taking both aspirin and NSAID, it is best to take the aspirin at least 4 hours before the NSAID for its full protective effect.

Arthritis of Systemic Disease Arthritis can be a component of many systemic diseases, including metabolic disorders, infections, malignancies, and various endocrine, hematologic, and GI diseases. Parvovirus


B19 is responsible for erythema infectiosum and can also cause polyarthritis, especially in the hands, knees, and ankles. HIV infection sometimes causes symmetric polyarthritis, spondylitis, or acute oligoarthritis. Hepatitis B and C can cause acute symmetric polyarthritis in large and small joints. Inflammation in a few large joints and back pain are among the earliest symptoms of infective endocarditis in about 25% of patients with this disorder (Totemchokchyakarn and Ball, 1996). Lyme arthritis caused by Borrelia burgdorferi can cause migratory monoarthritis or oligoarthritis in the knees or shoulders weeks to months after the rash of erythema chronicum migrans has developed. Poorly controlled diabetes (affecting foot, ankle, and knee), hyperthyroidism (affecting fingers and toes), hypothyroidism (causing noninflammatory effusions in knees, wrists, and hands), and parathyroid disease (causing chondrocalcinosis) are all endocrine disorders that can cause arthritis. Metabolic disorders can cause degenerative arthritis. Hemochromatosis (caused by iron deposition) typically affects the second and third metacarpophalangeal (MCP) joints, wrists, knees, hips, and shoulders. Wilson’s disease (caused by copper deposition) can cause premature OA in wrists and knees. Sickle cell disease can be complicated by knee arthritis; arthritis is also often seen in patients with hemophilia and leukemia. Arthritis is associated with inflammatory bowel disease and primary biliary cirrhosis. Reactive carcinoma synovitis can be the presenting symptom of an underlying malignancy, particularly of the breast or the prostate.

Referral to the Rheumatologist As for all types of disease conditions, referral to the subspecialist largely depends on the family physician’s knowledge, interest level, and logistical ability to provide state-of-theart care to a given patient for a given disease entity at a given time in the disease course. Specific conditions, such as suspected septic arthritis, acute myelopathy or mononeuritis multiplex, suspected acute tendon or muscle rupture, or acute internal derangement, should probably be referred. In addition, referral should be considered for patients without a specific diagnosis after 6 weeks; those with difficulty in symptom control, systemic symptoms in pregnancy, or severe symptoms; patients requiring steroid, immunosuppressive, or other drugs unfamiliar to the primary care physician; or those with end-stage joint disease. The often nonspecific nature and psychosocial impact of rheumatic symptoms require continued active involvement of the family physician in the patient’s care, regardless of referral.

Rheumatic Diseases Osteoarthritis Key Points • Osteoarthritis affects 20% of the U.S. population; 44% of OA patients are not active. • Primary and secondary OA must be differentiated. • NSAIDs, not COX-2 inhibitors, are still the pharmacologic treatment of choice for OA.

Osteoarthritis, also known as “degenerative joint disease,” is the most common form of arthritis and causes more work disability in the United States (17%) than any other disease. Arthritis affects 20% of the U.S. population, about half of whom primarily have OA. Long thought to result from “wear and tear,” OA is now known to have genetic, traumatic, metabolic, and developmental causes, which complicates prevention and treatment. OA is found radiographically in almost all 75-year-old patients, most of whom are asymptomatic. OA occurs about equally in men and women ages 45 to 55 but after 55 is more common in women (CDC, 2005). Most OA patients are not seriously affected and are asymptomatic. Others, however, require joint replacement surgery because of its severity. Although OA is considered a noninflammatory type of arthritis affecting primarily the cartilage, it actually involves active biochemical disease processes as well as mechanical forces that affect the entire synovial joint. An OA variant affecting primarily the hands runs in families and is inflammatory. Women are more prone to this inflammatory variant of OA of the hands that causes Heberden’s nodes (in distal interphalangeal [DIP] joints) and Bouchard’s nodes (in proximal interphalangeal [PIP] joints). The articular cartilage may not even be involved, with the disease process centered more on subchondral bone turnover (Peterson et al., 1998). Quadriceps muscle weakness might precede the onset of knee OA, indicating the importance of biomechanical factors (Slemenda et al., 1997). Osteoarthritis can be separated into primary (idiopathic), hereditary (resulting from collagen gene defects), and secondary. Secondary OA results from previous cartilage damage. Occupations causing repetitive joint trauma predispose a patient to OA. Episodic trauma, congenital anatomic abnormalities (slipped capital femoral epiphyses, congenital hip dysplasias), neuropathies, and endocrine-metabolic causes (obesity, hemochromatosis, Wilson’s disease, CPPD disease, Paget’s disease, acromegaly) all might lead to OA. Inflammatory arthritides such as RA, infections, or gout damage cartilage and are often followed by the development of OA. Occupational kneelers (e.g., shipyard workers, miners, carpet or floor layers) have a significantly higher incidence of knee OA than control groups of clerical workers (Maetzel et al., 1997). However, repetitive sports activities such as longdistance running are unlikely to cause OA in the absence of joint injury or antecedent joint abnormality (Panush and Lane, 1994). More than 44% of patients with diagnosed OA are inactive (Gordon et al., 1998). Low-impact activity in normal joints is not associated with OA, but high-intensity and high-impact activity resulting in injury is associated with OA. Mechanical risk factors might affect the initiation more than the progression of OA. Most mild OA does not progress to severe joint damage. Mild OA might be a different disease than severe OA, which depends on processes other than early OA.

Clinical Findings Most OA is asymptomatic, an incidental finding on radiographs performed for other reasons. No treatment or further evaluation is indicated for asymptomatic OA. Early symptomatic OA is characterized by local pain of gradual onset exacerbated by using the involved joint. Pain typically worsens as 655

32


the day progresses and is relieved by rest. There is less than 30 minutes of localized morning stiffness and no constitutional or systemic symptoms, and the gel phenomenon (stiffness after periods of rest and inactivity) resolves within several minutes of activity. Damp, cool, rainy weather often exacerbates symptoms because of changes in intra-articular pressure associated with changes in barometric pressure. Patients with OA of the knees might complain of buckling or instability, especially when descending stairs. OA of the hip can manifest as pain radiating from the groin and down the anterior thigh. OA of the neck might be felt in the neck, back, or upper extremities, causing pain, weakness, or numbness. As OA progresses, pain can become continuous, including at night. Primary OA can be divided into three classifications: generalized OA, large-joint OA, and erosive OA. Generalized OA involves five or more joints, most often the DIP joints of the hand (Herberden’s nodes), the PIP joints of the hand (Bouchard’s nodes), the first carpometacarpal joint, the first MTP joint of the feet, and the knee, hip, and spine. There is a significant familial component. Large-joint OA of the knees and hips might occur as part of generalized OA or alone. OA of the knees often occurs in the medial and patellofemoral compartments. OA of the hips can be characterized in two subsets, central and superior poles. Central or medial involvement of the hip joint space occurs in the setting of generalized OA, is usually bilateral, and is seen in women more than men. Most hip OA is superior pole, usually unilateral, seen more in men, and occurs without other joint involvement. As many as 40% to 90% of cases of adult hip OA might arise from subtle developmental abnormalities of the hip, including acetabular dysplasia, developmental (formerly “congenital”) hip dislocation, Legg-Calvé-Perthes disease, and slipped capital femoral epiphysis (Brandt and Slemenda, 2004). A rare form of primary OA known as erosive OA involves the hand’s PIP and DIP joints equally, with significant inflammation. Other joints are often not involved, although 15% of erosive OA cases might subsequently evolve into seropositive RA (Kujala et al., 1995).

Physical Findings Physical findings of OA typically include joint swelling, tenderness, crepitus, and enlargements at joint margins, causing deformity. The location of pain should be precisely localized as to whether it is truly articular or periarticular; if pain is located in the joint, an inflammatory or infectious cause should be ruled out first. Patients might have reduced ROM or, in severe cases, joint instability, resulting in excess motion or locking because of loose cartilage fragments. Warmth and soft tissue swelling because of joint effusion might be present, but a markedly swollen, hot, erythematous joint suggests a septic or microcrystalline disease rather than OA.

Laboratory Studies Clinical study criteria for OA classification are helpful as a means to standardize the diagnosis (see eTables 32-2 and 32-3 online). Although the diagnosis of OA can almost always be made by history and physical examination, definitive diagnosis can be helped by synovial fluid analysis, radiography, and normal ESR, ANA, and RF during symptomatic periods. Synovial fluid analysis of large-joint effusions can 656

be used to exclude other processes. Joint effusions in OA typically show leukocyte counts lower than 1000 WBCs/mm3, predominantly lymphocytes (Table 32-2). Serum tests might be misleading because ESR rises with age and 20% of healthy older adults have positive RF levels. A greatly elevated ESR suggests a process other than OA. Although many have been identified, biochemical markers of OA are not generally useful to the practicing clinician at this time.

Imaging Studies Radiographs are generally the first-line confirmation of the presence of OA. Treatment should not be based solely on radiographic abnormalities, however, given the frequency of asymptomatic joints demonstrating radiographic OA changes. OA changes include osteophyte formation, asymmetric joint space narrowing (defined as 50 years Stiffness 5 days plus four of the following five criteria: 1. Polymorphous rash 2. Bilateral conjunctival infection 3. One or more of the following mucous membrane changes: Diffuse infection of oral and pharyngeal mucosa Erythema or fissuring of the lips Strawberry tongue 4. Acute, nonpurulent cervical lymphadenopathy (one lymph node must be >1.5 cm) 5. One or more of the following extremity changes: Erythema of palms, soles, or both Indurative edema of hands, feet, or both Membranous desquamation of the fingertips Other illnesses with similar clinical signs must be excluded. From Freundlich B, Leventhal L. Diffuse pain syndromes. In Klippel JH (ed). Primer on the Rheumatic Diseases, 12th ed. Atlanta, Arthritis Foundation, 2001, p 409.

the palms and soles and desquamation of the fingertips. Most patients have cervical lymphadenopathy. A myocarditis is present in more than 50% of patients and is manifested by a tachycardia. Many other symptoms might also occur, such as respiratory, neurologic, and GI symptoms (Box 32-5). Because KS symptoms resolve spontaneously, cardiac manifestations might not be diagnosed. A coronary arteritis and even aneurysms might develop, with significant morbidity and mortality. Laboratory studies are not helpful. Serial electrocardiograms are recommended at diagnosis, 2 to 3 weeks into the illness, and 1 month after that. Although KS’s seasonal variation (winter and spring) and epidemics suggest an infectious cause, none has yet been identified. IV fluids, aspirin, and IVIG have been used most frequently for KS. Antibiotics are of no use unless there is a concomitant bacterial infection. Steroids might actually increase the incidence of aneurysms and should be avoided, if possible.

*Based on the Centers for Disease Control and Prevention case definition.

Nonarticular Rheumatism patient should be monitored for proteinuria and hematuria. Because of steroid side effects, immunosuppressant drugs are often used for severe cases.

Henoch-Schönlein Purpura Henoch-Schönlein purpura is a small-vessel vasculitis seen mostly in children. Immune complexes are deposited, causing petechiae, nephropathy, or renal disease (40%) and GI bleeding. The purpura is usually in dependent areas such as the buttocks and lower extremities. Affected children often present with abdominal pain after an upper respiratory infection. Symptoms typically resolve spontaneously without treatment within 2 weeks, but serious GI and renal involvement can occur, requiring steroids. NSAIDs might be helpful for arthralgias.

Kawasaki’s Syndrome Kawasaki’s syndrome (KS), also known as Kawasaki’s disease, is the leading cause of acquired heart disease in children. Prolonged high fever (up to 40° C [104° F]), with an urticaria-like rash and injection of mucous membranes, including a strawberry tongue, is followed by erythema of

Any pain and stiffness without true inflammation in the joint and with normal laboratory results in children is termed nonarticular rheumatism, or “growing pains.” These usually occur at night, last several hours, and often resolve spontaneously or are helped by massage or analgesics. Pain is sometimes felt behind the knees. No further evaluation is indicated unless pain occurs during the day. Overuse or hypermobile joints are two possible explanations; nonarticular rheumatism does not normally cause any reduction in activity.

Rheumatology Information on the Internet A great deal of information on rheumatic diseases for both physicians and patients can be found on the Internet. This can be a valuable tool for the family physician in this era of active research and new treatment modalities in rheumatology. Patients might receive online support from numerous advocacy and support groups for these conditions, although the Internet can also be a source of misinformation, with charlatans touting arthritis cures. Websites of the ACR, Arthritis Foundation, and Medline Plus are particularly good sources of information (see Web Resources).


Web Resources General Reference www.rheumatology.org American College of Rheumatology; Internet resources, academic and government sites, foundations/associations. www.arthritis.org Arthritis Foundation; excellent site, primarily for patients. 688

www.nlm.nih.gov/medlineplus/arthritis.html Medline Plus. www.curearthritis.org Arthritis National Research Foundation—information on financial support for research.

Rheumatology and Musculoskeletal Problems www.nih.gov/niams National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and National Institutes of Health (NIH)—conducting research in these areas.

Disease-Specific Sites www.aarda.org American Autoimmune Related Diseases Association—patient education. www.rheumatology.org/public/factsheets/fibromya_new.asp American College of Rheumatology—fibromyalgia. www.aldf.com American Lyme Disease Foundation.

www.lupus.org Lupus Foundation; patient advocacy, patient information, local chapters. www.myositis.org Myositis Association of America—polymyositis, dermatomyositis. www.risg.org Reiter’s Information and Support Group; patient education. www.sjogrens.com Sjögren’s Syndrome Foundation. www.spondylitis.org Spondylitis Association of America; patient education on ankylosing spondylosis, psoriatic arthritis, other types of spondylitis.

689

33 CHAP T E R Dermatology Richard P. Usatine and Jennifer Krejci-Manwaring

Chapter contents Principles of Diagnosis Initial Evaluation

690 690

General Management

692

Topical Corticosteroids Management of Pruritus

692 692

Skin Problems Beginning in Childhood Atopic Dermatitis (Eczema) Pityriasis Alba Keratosis Pilaris Melanocytic Nevi Infantile Hemangioma Acne Vulgaris Viral Exanthems

693 693 694 694 694 695 695 697

Inflammatory Dermatologic Diseases

698

Seborrhea Psoriasis Pityriasis Rosea Rosacea Lichen Planus Lichen Simplex Chronicus Contact Dermatitis Dyshidrotic Eczema (Pompholyx) Stasis Dermatitis Nummular Dermatitis (Nummular Eczema) Generalized Exfoliative Dermatitis Erythema Nodosum Granuloma Annulare

698 698 700 701 701 702 702 703 704 704 704 705 705

Infectious Skin Diseases Bacterial Infections Fungal Infections Viral Infections

Scabies Pediculosis Capitis (Head Lice) Pediculosis Corporis (Body Lice) Phthirus Pubis (Pubic Lice, Crab Lice)

Hypersensitivity Reactions and Other Eruptions “Morbilliform” (Maculopapular, Exanthemlike) Reaction Urticaria Erythema Multiforme Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Skin Signs of Systemic Disease Lupus Erythematosus Dermatomyositis Sarcoidosis

Benign Growths Seborrheic Keratosis Pyogenic Granuloma Epidermal Inclusion Cysts Dermatofibroma

Premalignant and Malignant Skin Lesions Actinic Keratosis Bowen’s Disease and Erythroplasia of Queyrat Basal Cell Carcinoma Squamous Cell Carcinoma Melanoma

716 716 717 718 718

718 719 719 719 720

720 720 722 722

723 723 723 724 724

724 724 725 726 727 728

705 705 708 713

Principles of Diagnosis Dermatologic diagnosis often begins with pattern recognition. Experts can look at most lesions and make an immediate and accurate diagnosis through pattern recognition. The basic terms used to describe lesion morphology and patterns provide the vocabulary to describe what is seen. The physician then combines keen observation of the lesions (including type and distribution) with a careful history to create an informed differential diagnosis. If the diagnosis is still not known, the physician can consult a dermatology atlas (online or print), textbook, or expert to complete the diagnosis. In some cases, further testing (scraping, culture, biopsy) may be needed. ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10033-8

Infestations

Initial Evaluation Although medical school teaches students to perform the history before doing the physical examination, this is not the most efficient way to approach the diagnosis of a skin condition. When the patient has a skin complaint, immediately look at the skin while asking your questions. Look carefully at the lesions and determine the lesion morphology. Table 33-1 provides definitions for the terms used to describe primary and secondary morphology. A magnifying glass and good lighting help to distinguish the morphology of many skin conditions. Next, touch the lesions, with gloves when appropriate. For some lesions, such as actinic keratosis with

Dermatology

Table 33-1 Primary and Secondary Skin Lesions

Lesions

Description

Primary (Basic) Lesions Macule

Circumscribed flat discoloration (up to 5 mm)

Patch

Flat nonpalpable discoloration (>5 mm)

Papule

Elevated solid lesion (up to 5 mm)

Plaque

Elevated solid lesion (>5 mm) (often a confluence of papules)

Nodule

Palpable solid (round) lesion, deeper than a papule

Wheal (hive)

Pink edematous plaque (round or flat), topped and transient

Pustule

Elevated collection of pus

Vesicle

Circumscribed elevated collection of fluid (up to 5 mm in diameter)

Bulla

Circumscribed elevated collection of fluid (>5 mm in diameter)

Figure 33-1 Vesicular tinea pedis leading to autosensitization reaction. (© Richard P. Usatine.)

Secondary (Sequential) Lesions Scale (desquamation)

Excess dead epidermal cells

Crusts

Collection of dried serum, blood, or pus

Erosion

Superficial loss of epidermis

Ulcer

Focal loss of epidermis and dermis

Fissure

Linear loss of epidermis and dermis

Atrophy

Depression in skin from thinning of epidermis/ dermis

Excoriation

Erosion caused by scratching

Lichenification

Thickened epidermis with prominent skin lines

scaling or the sandpaper rash of scarlet fever, lightly feeling the skin provides much information. For deeper lesions, such as nodules and cysts, deep palpation is needed. Observe the distribution of the lesions. Try to determine if the primary lesions are arranged in groups, rings, lines, or merely scattered over the skin. Determine which parts of the skin are affected and which are spared. Be sure to look at the remainder of the skin, nails, hair, and mucous membranes. Patients often show only one small area and appear reluctant to expose the rest of their skin, especially their feet. With many skin conditions, it is essential to look beyond the most affected area because other areas may provide important clues (e.g., nail pitting when considering psoriasis). Patients may have lesions on their back or feet that they have not observed. For example, a patient may have a papular eruption on the hands or arms that represents an autosensitization reaction (id reaction) to a fungal infection on the feet; not looking for the fungus on the feet will lead to a missed diagnosis (Figs. 33-1 and 33-2). Some skin diseases have manifestations in the

Figure 33-2 Autosensitization reaction secondary to vesicular tinea pedis (id reaction). (© Richard P. Usatine.)

mouth; finding white patches on the buccal mucosa may lead to the correct diagnosis of lichen planus (Fig. 33-3). Once the physician starts to look at the skin, the patient history will be more focused, directed toward finding the correct diagnosis. The following information assists in making a dermatologic diagnosis and planning treatment: • Onset and duration of skin lesions: continuous or intermittent? • Pattern of eruption: Where did it start? How has it changed? • Any known precipitants, such as exposure to medication (prescription, OTC), foods, plants, sun, topical agents, chemicals (occupation, hobbies)? • Skin symptoms: itching, pain, paresthesia • Systemic symptoms: fever, chills, night sweats, fatigue, weakness, weight loss • Underlying illnesses: diabetes, thyroid disease, human immunodeficiency virus (HIV) • Family history: acne, atopic dermatitis, psoriasis, skin cancers, dysplastic nevi The most important in-office examinations of the skin are the following: Microscopy. To diagnose a fungal infection, scrape some of the scale onto a microscope slide, add 10% potassium 691

33

Dermatology

Figure 33-3 Oral lichen planus showing Wickham’s striae. (© Richard P. Usatine.)

hydroxide (KOH) (best with dimethyl sulfoxide [DMSO] and fungal stain), and look for the hyphae of dermatophytes or the pseudohyphae of Candida or Pityrosporum species. Wood’s light examination. This is helpful in diagnosing tinea capitis and erythrasma. Tinea capitis caused by Microsporum spp. produces green fluorescence, but Trichophyton spp. do not fluoresce. Erythrasma has a coral-red fluorescence. Wood’s lamp also helps distinguish lesions of vitiligo in patients with fair skin. Surgical biopsy. The biopsy can be used as a diagnostic and treatment tool. Having a reasonable differential diagnosis will help the physician choose shave, punch, or elliptic biopsy.

General Management Topical Corticosteroids The choice of a topical steroid involves maximizing benefit and minimizing adverse effects. Many skin conditions benefit greatly from topical steroids. However, local adverse effects of topical steroids are common with regular use over weeks to months. The most common adverse effect of topical steroids is skin atrophy, in which the epidermis becomes thin and the superficial capillaries dilate. Epidermal atrophy can be accompanied by hypopigmentation and telangiectasias. If atrophy involves the dermis, striae may occur. Although the epidermal atrophy may be reversible in months, striae are irreversible. When fluorinated steroids (the strongest steroids) are continuously applied to the face, perioral dermatitis, rosacea-like eruptions, and acneiform eruptions can occur. Systemic adverse effects are rare and occur when large amounts of topical steroids are absorbed systemically. The risk of such absorption increases with stronger steroids, thinner skin, younger patients, longer duration of therapy, and the use of occlusion in therapy. Prescribing the minimum strength needed for the shortest duration required helps prevent adverse effects. In choosing the best topical steroid, consider the following factors: 1. Skin disorder. As the severity of the disorder increases, the need for higher-potency steroids increases. Also, thicker lesions (e.g., psoriatic plaques, lichen planus) need higher-potency steroids. 692

2. S ite. Use only the weakest-potency steroids on the face, genitals, and intertriginous areas, where skin is thin or moist and skin atrophy and striae occur most rapidly. There are exceptions, however, as when clobetasol is needed to treat certain vulvar disorders. The skin on the palms and soles is so thick that the most potent steroids may be needed. 3. Age. Avoid the use of high-potency topical steroids in infants and children because they have greater surface area per body mass than adults and have greater risk and consequences of systemic absorption. 4. Steroid potency (strength and concentration). There are more than 50 types and brands of steroids; family physicians should know at least one steroid from each of four basic strengths (Table 33-2). Generic agents can be used from all the potency groups to save on costs. 5. Vehicle. The vehicle is the substance in which the steroid is dispersed. The most common vehicles are ointments, creams, gels, solutions, lotions, and foams. The choice of vehicle is determined by the characteristics of the lesion (dry or moist), the site involved, and patient preference. Further, the vehicle affects the potency of the steroid because it determines the rate at which the steroid is absorbed through the skin. Most skin preparations can be applied two times a day (bid), conveniently in the morning and evening. Try to estimate and prescribe an appropriate amount; many topical products are supplied in 15-gram, 30-g, 60-g, and 80-g sizes; 80 g is about the size of a tube of toothpaste. Based on common practice, it is accepted that 2 g of cream is required to cover the face or one hand, 3 g for an arm, 4 g for a leg, and 12 to 30 g for an entire body. To avoid adverse effects of steroid overuse, do not prescribe large quantities for small lesions, and specify duration of use. On the other end of the spectrum, prescribing only 15 g of steroid for a large area of involvement will be frustrating to the patient when the steroid is depleted before completing the prescribed treatment. Generic triamcinolone comes in 1-pound tubs (454 g), extremely helpful for patients with inflammatory conditions covering much of the body. The duration of therapy is usually the time required for resolution of symptoms or lesions. To avoid adverse effects, the highest-potency steroids should not be used for longer than 2 to 4 weeks continuously. However, these can be used intermittently for chronic conditions such as psoriasis in a pulsetherapy mode (e.g., apply every weekend, with steroid-sparing medication on weekdays). For conditions with dry skin, liberal use of emollients between steroid applications can minimize steroid exposure while maximizing the benefits of therapy.

Management of Pruritus Often, patients present because of the pruritus associated with a skin condition rather than the skin condition itself. Itching associated with visible lesions often responds to relatively nonspecific antipruritic treatments. If the itching is generalized, patients may obtain temporary relief from cool or tepid baths with the addition of colloidal oatmeal (Aveeno). Soap should be avoided. Oral antihistamines can be given every 6 to 8 hours, especially at bedtime to promote sleep. Diphenhydramine (Benadryl) and hydroxyzine (Atarax, Vistaril) are first-generation antihistamines that are relatively

Dermatology

Table 33-2 Potency of Topical Corticosteroids

Potency

Generic Drugs

Brand Names

“Superpotent” (class 1)

Clobetasol, betamethasone dipropionate, halobetasol, fluocinonide

Clobex, Diprolene, Olux, Psorcon, Temovate, Ultravate, Vanos

High potency (classes 2 and 3)

Betamethasone dipropionate, mometasone, halcinonide, fluocinonide, desoximetasone, triamcinolone 0.1%, fluticasone, amcinonide

Diprolene, Elocon, Halog, Lidex, Psorcon, Topicort, Aristocort, Cutivate, Cyclocort

Midpotency (classes 4 and 5)

Prednicarbate, mometasone, betamethasone valerate, hydrocortisone probutate, fluocinolone, desoximetasone, hydrocortisone valerate, triamcinolone 0.025%

Dermatop, Elocon, Luxiq, Pandel, Synalar, Topicort, Westcort, Cordran, Cutivate, Locoid

Low potency (classes 6 and 7)

Alclometasone, desonide, fluocinolone, hydrocortisone

Aclovate, DesOwen, Synalar, Hytone, Desonate

Figure 33-4 Atopic dermatitis. (© Richard P. Usatine.)

safe and effective, although caution should be used in older adult patients. Second-generation antihistamines are similarly effective for reducing pruritus in the daytime, and are less sedating for some patients. These include fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec). Usually, second-generation antihistamines are given once daily.

Skin Problems Beginning in Childhood Atopic Dermatitis (Eczema) Key Points • A topic dermatitis is a common inherited childhood disorder that may occur with other atopic conditions such as allergic rhinitis and asthma. • Topical steroids and emollients are the mainstays of treatment for AD. • Topical and systemic antibiotics are used for AD secondarily infected with bacteria.

Atopic dermatitis (AD) is a potentially debilitating condition that can compromise quality of life. Its most frequent symptom is pruritus. Pruritus leads to scratching, resulting in secondary skin changes such as lichenification, excoriation, and breakdown of the skin barrier. Consequently, atopic dermatitis has been referred to as “the itch that rashes.” Atopic dermatitis is a common problem affecting up to 15% of all children. In most cases, AD occurs before 5 years of age, frequently on the face in the first year of life (Fig. 33-4). As children grow, the antecubital and popliteal fossae are often involved (Fig. 33-5). The disease may occur

Figure 33-5 Atopic dermatitis in antecubital fossa. (© Richard P. Usatine.)

intermittently between periods of complete remission. By adulthood, the incidence becomes less than 1%. Treatment should be directed at limiting itching, repairing the skin, and decreasing inflammation. Lubricants and topical corticosteroids are the mainstays of therapy. Topical pimecrolimus or tacrolimus are considered steroid-sparing agents and are effective for short-term use or in cases unresponsive to topical corticosteroids. These agents are only approved for second-line treatment in patients over 2 years of age. When required for severe cases, oral corticosteroids can be used. If pruritus does not respond to treatment, other diagnoses, such as bacterial overgrowth or viral infections, should be considered. Always look for signs of bacterial superinfection, such as weeping of fluid and crusts (Fig. 33-6). Superinfection with Staphylococcus aureus may lead to worsening of atopic dermatitis as the bacteria functions as a super antigen. S. aureus superinfections are usually sensitive to methicillin, so oral cephalexin is frequently a good choice for treatment. Bleach baths are helpful to cut down on colonization. (Add 1⁄2 cup regular bleach per full tub of lukewarm water and soak for 5 to 10 minutes before washing off bleach water.) 693

33

Dermatology

Figure 33-6 Impetiginized atopic dermatitis. (© Richard P. Usatine.)

KEY TREATMENT Topical steroids and emollients are the mainstay of treatment for atopic dermatitis (Hanifin et al., 2004) (SOR: A). Topical and systemic antibiotics are used for AD with secondary bacterial infection; weeping fluid and crusting during an exacerbation should prompt consideration of antibiotic use (Hanifin et al., 2004) (SOR: A). Topical calcineurin inhibitors (immunomodulators such as pimecrolimus and tacrolimus) reduce the rash severity and symptoms of AD in children and adults (Hanifin et al., 2004) (SOR: A). Dietary restriction is useful only for infants with proven egg allergies (Hanifin et al., 2004) (SOR: B). The value of antihistamines in AD is controversial; if used, the sedating agents are most effective and can be given at night (Hanifin et al., 2004) (SOR: B).

Pityriasis Alba Pityriasis alba is a common hypopigmented dermatitis that may affect nearly one third of school-age children in the United States. The condition is more common in patients with a history of atopic dermatitis. Patients present with numerous hypopigmented macules ranging from 1 to 4 cm in size on the face, neck, and shoulders (Fig. 33-7). The macules are poorly defined and may have fine scales. Occasionally, erythema and pruritus occur before the lesions. Generally, pityriasis alba is self-limited and asymptomatic, so therapy is typically unnecessary. Lesions usually fade by adulthood. Topical steroids, emollients, and phototherapy have limited efficacy. Hydrocortisone 1% cream or ointment may provide some benefit, and if used for no more than 2 weeks, the patients should be relatively safe from adverse effects.

Keratosis Pilaris Keratosis pilaris is very common and presents as tiny (3), moles (nevi) or dysplastic nevi, family or personal history of melanoma, immunosuppression, and older age. • One third of melanomas arise in a preexisting nevus. • Depth of tumor invasion is the most important prognostic indicator for melanoma; most patients with thin tumors (0.5 ml/min)

Positive EGD: see UGIB algorithm

Successful angiography (embolization or intraarterial injection)

Persistent bleeding

Observation

Surgery

Figure 38-26 Algorithm for the management of acute lower gastrointestinal bleeding (part 1). CBC, Complete blood count; UGIB, upper gastrointestinal bleeding; PEG, percutaneous endoscopic gastrostomy; EGD, esophagogastroduodenoscopy. (Modified from Eisen GM, Dominitz JA, Faigel DO, et al; American Society for Gastrointestinal Endoscopy, Standards of Practice Committee. An annotated algorithmic approach to acute lower gastrointestinal bleeding. Gastrointest Endosc 2001; 53:859-863.)

exploration. Directed segmental resection is advised when the bleeding site is identified preoperatively, as seen in adenocarcinoma of the colon or diverticular disease limited to the left colon with persistent or recurrent bleeding. The removal of identified colonic lesions does not always result in effective treatment of the underlying source of bleeding. In these cases, arteriography can be used intraoperatively as an adjunct to localize a source of bleeding, facilitate segmental resection of the bowel, and prevent “blind hemicolectomy” (Manning-Dimmitt et al., 2005). A transfusion requirement of greater than 4 units of packed RBCs in 24 hours and recurrent diverticular bleeding (seen in up to 30% of patients) are common indications for surgical intervention. Other factors, such as comorbidities and individual surgical practices, play a significant role in this decision (Eisen et al., 2001). In patients with chronic intermittent rectal bleeding, upper endoscopy is the preferred test for evaluation, with sensitivity and specificity of 92% and 100%, respectively. A barium-contrast upper GI series with small bowel followthrough (SBFT) may be considered if there is a relative contraindication to endoscopy (e.g., anticoagulation therapy, high risk for complications with conscious sedation, endoscopist unavailable). This test has sensitivity and specificity of 54% and 91% in the detection of upper GI lesions located above the ligament of Treitz (Zuckerman et al., 2000). Transcatheter embolization is an alternative when vasopressin is unsuccessful or contraindicated, but carries a risk of

acute abdominal pain and intestinal infarction (Eisen et al., 2001). Small intestinal sources of GI bleeding account for less than 10% of all cases. When upper and lower endoscopy have failed to determine the suspected cause of bleeding, the physician should consider push enteroscopy (extension of upper endoscopy that allows visualization of up to 160 cm of small bowel distal to ligament of Treitz), although this procedure is limited by its inability to visualize the entire small bowel and thus carries a low diagnostic yield. The barium-contrast upper GI series with SBFT carries a very low sensitivity of zero to 5.6%. Enteroclysis (endoscopic placement of radiopaque contrast directly into proximal small bowel) also has low sensitivity, but has a shorter procedure time and can be used in the unconscious or uncooperative patient. Enteroclysis combined with push enteroscopy has higher diagnostic sensitivity than either method alone. Arteriography can be used in challenging cases to evaluate bleeding not identified by endoscopy. It is particularly helpful in the evaluation of older patients in whom arteriovenous malformations (AVMs) or neoplasms are suspected, because both of these lesions are associated with characteristic vascular patterns that can be identified on arteriogram. Capsule endoscopy is being studied as another modality for identifying small bowel bleeding and neoplastic pathology, but is limited in that biopsy samples cannot be obtained. Enhanced helical CT scanning is being explored as an alternative means of evaluating GI bleeding. Laparotomy with intraoperative 869

38

Gastroenterology ACUTE LOWER GI BLEEDING (PART 2) Colonoscopy

Source of bleeding identified

AVM’s

Endoscopic therapy

Persistent recurrent bleeding

Diverticulosis

Unable to visualize colon endoscopically due to severity of bleeding

Other lesions

Bleeding stopped

Consider elective surgery if >4 UPRBC in 24 hrs of prior h/o diverticular bleed

See part 1

Angiography

Continued bleeding

Surgery

Bleeding stopped

Bleeding continues

Faster bleeding angiography (>0.5 ml/min)

Persistent or recurrent bleeding

Slower bleeding TRBC scan (>0.1 ml/min)

Positive

Source of bleeding not identified

Evaluation of small bowel EGD if not previously done; consider repeat colonoscopy

Negative

Bleeding continues

Bleeding stopped

Preoperative localization Angiography or surgery

Endoscopic therapy

Surgery

Figure 38-27 Algorithm for the management of acute lower gastrointestinal bleeding (part 2). AVM, Arteriovenous malformation; UPRBC, units of packed red blood cells; TRBC, tagged (radiolabeled) red blood cell. (Modified from Eisen GM, Dominitz JA, Faigel DO, et al; American Society for Gastrointestinal Endoscopy, Standards of Practice Committee. An annotated algorithmic approach to acute lower gastrointestinal bleeding. Gastrointest Endosc 2001;53:859-863.)

enteroscopy should be considered a “last resort” in the diagnostic evaluation of nonemergent cases of GI bleeding because it is associated with higher rates of morbidity and mortality (Zuckerman et al., 2000).

KEY TREATMENT Colonoscopy is the preferred modality used in the treatment of lower GI bleeding (Zuccaro, 1998) (SOR: A).

Diverticular Disease Diverticulosis refers to the presence of diverticula, or herniations of the intestinal mucosa and submucosa, most often in the sigmoid colon (Figs. 38-28 and 38-29). More than one half of patients over age 50 have incidental colonic diverticula. Diverticulitis is the most common complication of diverticulosis, occurring in up to 20% of patients, and results from a microperforation of a diverticulum from inspissated fecal material that often becomes a phlegmon, or a pericolic or intra-abdominal abscess. The initial assessment of the patient with suspected divertic ulitis should include a thorough history and physical examination, including abdominal, rectal, and pelvic examinations. 870

The majority of patients will have LLQ pain (93%-100%), fever (57%-100%), and leukocytosis (69%-83%). Other associated features include nausea, vomiting, constipation, diarrhea, dysuria, and urinary frequency. The differential diagnosis includes IBS, IBD, colon cancer, ischemic colitis, bowel obstruction, and gynecologic and urologic disorders (ASCRS, 2000). Initial evaluation of the patient with abdominal pain and suspected diverticulitis includes CBC, urinalysis, and flat and upright abdominal radiographs. The American Society of Colon and Rectal Surgeons Standards Task Force for the treatment of diverticulitis state that if the patient’s clinical picture clearly suggests acute diverticulitis, the diagnosis can be made on the basis of clinical criteria alone (ASCRS, 2000). The need for additional tests in the patient with suspected diverticulitis is determined by the severity of the presenting signs and symptoms and diagnostic confidence. When the diagnosis of diverticulitis is in question, other tests may include water-soluble contrast enema, abdominal CT, or ultrasonography. Criteria for the diagnosis of diverticulitis on water-soluble contrast enema include the presence of diverticula (Figs. 38-30 and 38-31), mass effect, intramural mass, sinus tract, and extravasation of contrast. Ultrasound may reveal bowel wall thickening, abscess, and rigid hyperechogenicity of the colon caused by inflammation and may be helpful in female

Gastroenterology

Table 38-4 Causes of Massive Acute Rectal Bleeding

Cause

Frequency (%)

Upper GI Tract Peptic ulcer disease

40-79

Gastritis, duodenitis

5-30

Esophageal varices

6-21

Mallory-Weiss tear

3-15

Esophagitis

2-8

Gastric cancer

2-3

Dieulafoy’s lesion

100 mg/m2/day Adults 30-300 mg/24 hr—microalbuminuria >300 mg/24 hr—albuminuria >3.5 g/24 hr—nephritic-range proteinuria

From Weiss JP, Blaivas JG. Nocturia. J Urol 2000;163:5-12.

interventions include avoiding excess nighttime alcohol or fluid intake and afternoon napping. Adjusting diuretic doses so they are given earlier in the evening should negate medication effects during sleep (Weiss and Blaivas, 2000).

Proteinuria The kidneys normally excrete a small amount of protein daily, usually glycoproteins. Only very small amounts of globulins, light-chain proteins, or albumin are released. Functional proteinuria may result from physiologic changes in glomerular filtration, as occurs with exercise (Venkat, 2004). However, consistent albuminuria implies glomerular or tubular dysfunction. The urine dipstick is the most convenient measurement, but a more accurate test is the Upr/UCr ratio, obtained by dividing the random urine sample protein level by the urine creatinine level (both in mg/dL). This ratio has proven correlation with 24-hour excretion rates (Ginsberg et al., 1983). Thus, random urine samples are the best way to identify and follow proteinuria, and 24-hour collections are usually not needed (Levey et al., 2003) (Table 40-3). However, results from those with low or high levels of muscle mass may not correlate as well with 24-hour measurements (Venkat, 2004).

Proteinuria in Adults Proteinuria is a marker of kidney disease in adults and may actually contribute to renal impairment. Patients with diabetes should be periodically tested for microalbuminuria. Others at risk for kidney disease, such as patients with hypertension, should also be tested. 908

*Urine

protein/creatinine ratio.

Adults with proteinuria need their UPr/Ucr determined. Those with values outside the normal range should undergo an evaluation for CKD (see later). Patients with dipstick proteinuria but normal-range UPr/UCr values should be rechecked at periodic follow-up (Fig. 40-7).

Proteinuria in Children and Adolescents Most proteinuria in children is transient when followed up with weekly urine sample testing. Persistent proteinuria found in at least two of three weekly urine samples warrants further evaluation to identify those children who may have chronic renal disease. Proteinuria in children may be classified as functional, isolated, or symptomatic. Functional proteinuria may occur with fever or exercise. Isolated proteinuria is defined by the absence of abnormal history, physical examination findings, symptoms, or other urinary abnormalities. The most common cause of this form is benign orthostatic proteinuria, defined by normal protein excretion overnight or in the supine position. The initial evaluation for isolated proteinuria involves obtaining a first-morning urine sample for protein and creatinine as well as a formal urinalysis for microscopy review (Hogg et al., 2000). The absence of morning proteinuria, as evidenced by normal UPr/UCr, supports the diagnosis of benign orthostatic proteinuria. A more accurate assessment is a split 24-hour urine collection for protein. Benign orthostatic proteinuria may be transient or fixed and in either case has an excellent prognosis (Springberg et al., 1982). In contrast, nonorthostatic isolated proteinuria with a duration of 1 year or longer may represent significant renal pathology (Trachtman et al., 1994). Thus, these patients need yearly or twice-yearly clinical follow-up with assessment of blood pressure, renal function, serum albumin, urine microscopy, and urine protein. Pathologic proteinuria, whether isolated or symptomatic, occurs in the setting of a variety of glomerular and tubulointerstitial diseases (Box 40-5). Some children may present with the nephrotic syndrome (proteinuria, hypoalbuminemia, edema). Depending on the degree of proteinuria and the results of the initial laboratory evaluation, a renal biopsy may be indicated (Fig. 40-8).

Urinary Tract Disorders

Evaluation for proteinuria Not at ↑ risk

Standard dipstick ≥1+

Negative/trace

At ↑ risk

Albumin-specific dipstick Negative

Albumin/creatinine ratio

Total protein/creatinine ratio ≤200 mg/g

>200 mg/g

Positive

≤30 mg/g

Recheck at periodic health evaluation Diagnostic evaluation

Treatment

>30 mg/g

Consultation

Figure 40-7 Approach to proteinuria in adults. (Modified from Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;139:137-147, E148-E149. Redrawn from National Kidney Foundation/Kidney Disease Quality Initiative. See Web Resources.)

Proteinuria confirmed on repeat dipstick

Box 40-5 Causes of Pathologic Proteinuria in Children

Glomerular Disease Minimal-change disease Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative glomerulonephritis IgA nephropathy Lupus nephritis Alport’s syndrome Diabetic nephropathy Hypertensive nephropathy

Tubulointerstitial Disease Obstructive uropathy Reflux nephropathy Polycystic kidney disease Interstitial nephritis Pyelonephritis Acute tubular necrosis Proximal tubulopathy

Anatomic Disorders Key Points • P renatally identified hydronephrosis may be caused by underlying urinary tract obstruction. These infants need close follow-up with ultrasound in the first week of life. • Hydroceles in infants often resolve by age 2 years. Hydroceles in adults may have a secondary cause. • Reassure patients with Peyronie’s disease that it is usually selflimited.

1st AM UPr:UCr ratio or split 24hr urine and U/A with micro

Orthostatic proteinuria with negative U/A?

Yes Yearly follow up with 1st AM urine

No Urine culture Electrolytes, BUN, creatinine, albumin, C3, C4, ANA Hepatitis B and C screens Renal ultrasound

Figure 40-8 Approach to the child with proteinuria. ANA, Antinuclear antibody; BUN, blood urea nitrogen; U/A, urinalysis; UPr:UCr, urine protein/ urine creatinine.

• T esticular torsion is a medical emergency. Torsion of the appendix testis is less severe and can be managed with supportive care. • Undescended testes increase the risk for testicular cancer in the undescended as well as contralateral testicle.

Anatomic urinary tract disorders involve various congenital and acquired abnormalities, most notably of the external genitalia. Testicular disorders are seen more often than abnormalities of the penis, particularly undescended testes. Anatomic derangements of the bladder, ureter, and kidney are often only discovered incidentally or during an evaluation 909

40


for UTIs, voiding problems, CKD, or pain possibly related to the urinary tract. For example, posterior urethral valves cause vesicoureteral reflux and may contribute to recurrent UTIs (see Urinary Tract Infections in Children). Scrotal masses are frequently encountered in family medicine. Anatomic causes of scrotal masses are not limited to the urinary tract, and neoplastic and infectious causes are also in the differential diagnosis (Table 40-4). Scrotal or testicular pain, the so-called acute scrotum, implies a more urgent or emergent cause (e.g., testicular torsion). Because the history and physical examination may not be adequate to differentiate certain conditions (e.g., epididymo-orchitis from testicular torsion), adjunctive imaging such as ultrasound is often used.

Fetal Hydronephrosis With the pervasive use of fetal ultrasound, hydronephrosis is more often diagnosed prenatally. A dilated renal collecting system is often the only indication of a number of congenital uropathies (Ismaili et al., 2004). Two processes cause hydronephrosis, reverse urine flow (vesicoureteral reflux, VUR) and impaired forward urine flow (obstruction). VUR occurs as an isolated entity or can be associated with a more complicated uropathy, such as bladder outlet obstruction with VUR. Obstructive uropathy may occur at different sites along the urinary tract, most often the ureteropelvic junction (UPJ). Infants with fetal hydronephrosis need an ultrasound in the first week of life. If normal, a repeat ultrasound should be done in 2 to 4 weeks because of the possibility of a falsenegative study in the low urine flow state characteristic of the newborn (Becker and Avner, 1995). Once the diagnosis is confirmed, evaluation includes a urinalysis, urine culture, basic metabolic panel (if bilateral), and a VCUG. If the VCUG is normal, a furosemide renogram is needed to determine the presence and degree of obstruction.

Table 40-4 Selected Differential Diagnosis of Scrotal Masses with Physical Findings

Abnormality

Physical Finding

Epididymitis, orchitis

Tender mass

Hydrocele

Transilluminates

Inguinal hernia

Does not transilluminate

Testicular torsion

Pain and loss of cremasteric reflex

Torsion of the appendix testis

Blue dot sign

Trauma

Tender scrotum, edema, trauma history

Tumor

Solid mass

Spermatocele

Nontender cystic mass

Varicocele

Bag of worms appearance

Figure 40-9 Hypospadias. (From Borer JG, Retik AB. Hypospadias. In Wein AJ [ed].

Hydrocele Hydroceles are fluid accumulations in the tunica vaginalis and can be primary, resulting from a failure of the processus vaginalis to close during development, or secondary to epididymitis, orchitis, testicular torsion, trauma, or tumors (Brenner and Ojo, 2004). Hydroceles typically transilluminate, whereas inguinal hernias do not. In young children, management is supportive, with the hydrocele often resolving by age 2 years. Hydroceles presenting beyond 2 years or those associated with inguinal hernias require surgical consultation. Also, some hydroceles are communicating; that is, fluid can pass from the peritoneal cavity into the hydrocele. These may change in size with activity or during the day and need surgical evaluation (Schneck and Bellinger, 2007). Hydroceles arising de novo in adults often have a secondary cause and require evaluation (Dogra et al., 2003).

Hypospadias Hypospadias, in which the urethra opens on the underside of the penis, is infrequently seen (Fig. 40-9). However, it is important that hypospadias is recognized early, preferably at the initial newborn examination. It can occur with or 910

Campbell-Walsh Urology, 9th ed, vol IV, Philadelphia, Elsevier, 2007.)

without chordee (curvature). Circumcision should be withheld and a urology consultation obtained. Hypospadias must be differentiated from ambiguous genitalia, which implies an intersex disorder. Epispadias, in which the meatus is located on the dorsal surface of the penis, is uncommon and is usually associated with extrophy of the bladder.

Labial Adhesions Labial adhesions may be seen in young girls and may be partial or complete (fusion) and asymptomatic. However, labial adhesions can be associated with difficult or abnormal urination and may contribute to the development of UTIs. It is important to perform an external genital examination in the female with her first UTI (Fig. 40-10). Retrospective data and case series support topical estrogen cream to the affected areas, with gentle traction until the adhesions have separated (Bacon, 2002). In a recent study, however, labial separation occurred more quickly and with less recurrence in patients treated with betamethasone than in those treated with estrogen cream (Mayoglou et al., 2009).


Figure 40-11 Paraphimosis. (From Kleigman R, et al. Nelson Textbook of Pediatrics, ed 18. Philadelphia, Saunders-Elsevier, 2007, p 2256.) Figure 40-10 Techniques for pediatric female genital examination. (From Canning DA, Nguyen MT. Evaluation of the pediatric urologic patient. In Wein AJ [ed]. Campbell-Walsh Urology, 9th ed, vol 1. Philadelphia, Saunders, 2007.)

Peyronie’s Disease Peyronie’s disease is characterized by formation of fibrosis in the tunica albuginea, with resulting penile deformity and pain. Symptoms include painful erection, physical penile deformity (often curvature), palpable penile plaque (fibrosis), and erectile dysfunction. Pain is typically transient, and most cases do not result in a deformity so severe that it impairs intercourse. Sexual history, counseling, and partner involvement are important, because Peyronie’s disease can be disruptive to a relationship. Most patients do not require any treatment beyond reassurance and counseling. Nonsurgical treatments are available (e.g., colchicine, intralesional verapamil), but supporting evidence is limited, and urologic consultation should be considered before exploring treatment. Steroid injection is best avoided. Surgery is an option in severe cases (Lewis and Munarriz, 2007).

Phimosis and Paraphimosis Phimosis (inability to retract foreskin over glans) and paraphimosis (inability to return retracted foreskin over glans) are possible complications seen in the uncircumcised male (Fig. 40-11). About 50% of boys typically are able to retract their foreskin by 1 year of age and 80% by age 3 (Anderson and Anderson, 1999). Topical estrogen therapy has been reported as successful, but no randomized trials support its use (Yanagisawa et al., 2000). However, low-potency topical corticosteroid therapy combined with daily prepuce retraction appears effective for phimosis (Zampieri et al., 2005). Because vascular engorgement leads to necrosis of the glans, acute paraphimosis needs urgent medical attention. A dorsal slit procedure may be required if other reduction techniques are unsuccessful. Ice packs and plastic wrap may

reduce the edema enough to allow manual reduction (Choe, 2000). Circumcision is generally indicated after the reduction and edema resolution. Methods of reduction included manual, osmotic, puncture and aspiration (Little and White, 2004).

Spermatoceles Spermatoceles (epididymal cysts) are painless cysts filled with sperm and can be palpated distinct from the testis. They transilluminate, are generally of no consequence, and do not affect fertility.

Testicular Disorders Testicular Torsion Although occasionally seen in the newborn male, testicular torsion is an acquired condition seen during puberty and is an emergency. It usually presents with abrupt onset of severe scrotal pain, at times waking the patient up in the early morning. Associated signs and symptoms include fever, nausea, vomiting, and abdominal pain. Intermittent testicular torsion has been described. On physical examination, the testis may lie in a more horizontal position, caused by a lack of normal attachment to the tunica vaginalis (“bell clapper” deformity), and demonstrate a loss of the cremasteric reflex. The diagnosis of testicular torsion can be made by physical examination or with the assistance of color Doppler ultrasound; however, physical examination is unreliable for ruling torsion in or out (Schmitz and Safranek, 2009). Timeliness of the diagnosis is critical, because testicular viability declines to 0% if detorsion occurs 24 hours after the onset of symptoms (Brenner and Ojo, 2004). Testicular torsion can occur in systemic illnesses, such as Henoch-Schönlein purpura, or can mimic the symptoms of other conditions, such as appendicitis or nephrolithiasis. 911

40


Torsion of the appendix testis presents similar to testicular torsion, although the symptoms are not as severe. The classic patient is a boy age 7 to 12 years. Palpation of the testis is normal except for a small, tender, palpable mass located on the superior or inferior pole. The cremasteric reflex is intact. The “blue dot” sign may be present and represents the compromised appendix testis as viewed through the scrotum. Diagnosis is generally made clinically and treatment is supportive, including analgesia and scrotal elevation. It is not unusual for the pain to last 5 to 10 days, but chronic pain may occur and warrants urology consultation.

• A nticholinergic drugs and trospium are effective treatments for urge incontinence. • Anticholinergic drugs for an overactive bladder may not have clinically significant benefits and often cause dry mouth. • Men with recurrent kidney stones and idiopathic hypercalciuria should be on a low-sodium, low-protein diet. Low-calcium diets do not reduce stone formation. • Non-contrast-enhanced CT is the test of choice for diagnosing kidney stones.

Chronic Kidney Disease Undescended Testis Undescended testis (testes) occurs in 2.7% to 5.9% of fullterm male infants, decreasing to 1.2% to 1.8% by age 1 year (Pillai and Bassner, 1998); the incidence is higher in premature infants. An undescended testis must be differentiated from a retractile testis, which may occur as the cremasteric reflex is developed. As opposed to an undescended testis, a retractile testis can be manually coaxed into the scrotum. In general, the patient with truly undescended testes needs urology evaluation. Failure to respond to human chorionic gonadotropin (hCG) is an indication for orchiopexy, especially if the testes have not descended by the first birthday. This should be accomplished before the child is 6 years old. The testicular examination should be taught to orchiopexy patients because of the slightly increased risk of cancer in either testicle (Altman, 1967).

Varicoceles A varicocele is a collection of dilated and tortuous veins surrounding the spermatic cord. It is most often asymptomatic and left-sided. Varicoceles arise in adolescence and are estimated to occur in 10% to 15% of the male population (Schneck and Bellinger, 2007). Evidence that varicoceles cause infertility is limited, but they are found in 12% of men presenting with infertility and in mature adolescents with varicoceles, 26% had abnormal semen analyses (Brenner and Ojo, 2004; Biyani et al., 2009). The “bag of worms” appearance on scrotal examination is the hallmark of this diagnosis. Inferior vena cava obstruction should be considered if the varicocele is right sided, of acute onset, or occurs in a prepubertal boy.

Functional Disorders Key Points • P atients with proteinuria and elevated Upr/UCr should be evaluated for chronic kidney disease. The serum creatinine level may not correlate with glomerular filtration rate; GFR estimates are adequate to diagnose kidney disease; 24-hour urine testing is usually not needed. • Patients with chronic kidney disease need systemic management. • Enuresis typically resolves with age. A bed-wetting alarm is effective if treatment is needed. • Erectile dysfunction has many causes and may be a marker of vascular disease. • Pelvic floor muscle exercises are first-line treatment for stress and mixed urinary incontinence. 912

Renal disease is a significant public health burden, with almost 20 million persons in the United States having chronic kidney disease (Coresh et al., 2003). In 2002 the National Kidney Foundation issued guidelines on the evaluation and management of CKD. The centerpiece of this new approach is defining CKD as kidney damage or decreased kidney function for 3 months or longer (Levey et al., 2003). Proteinuria is a clinical sign of kidney disease. Patients with proteinuria should be approached as described earlier. Patients with abnormal urinary protein values (e.g., UPr/ UCr) or other markers of kidney damage should be assessed for CKD (Johnson et al., 2004). The primary measure of kidney function is the glomerular filtration rate (GFR), and the stages of CKD are based on GFR (calculated by CockcroftGault or MDRD equation) (Table 40-5). The modification of diet in renal disease (MDRD) equation performs as well or better than measured creatinine clearance (Levey et al., 1999). However, physicians should be aware that the values obtained by the equations may differ slightly, and the Table 40-5 Stages of Chronic Kidney Disease

Stage

Defining Features

GFR† (mL/min/1.73 m2)

1

Kidney damage,* normal GFR

≥90

2

Kidney damage, mild decrease in GFR

60-89

3

Moderate decrease in GFR

30-59

4

Severe decrease in GFR

15-29

5

Kidney failure

65 yr); 100 mg/24 hr; take 0.5-4 hr before intercourse.

Common—headache, flushing, dyspepsia, nasal congestion, abnormal vision; serious—priapism Caution if sexual activity or exertion risky because of existing cardiovascular disease; caution with potent CYP3A4 inhibitors; caution in renal, hepatic impairment; caution in older adults (>65 yr); caution with α-blockers.* Nitrates

Tadalafil (Cialis)

2.5, 5, 10, 20 mg Up to 36 hr

Daily use: 2.5 mg, may increase to 5 mg PRN use: 10 mg, 1 dose/24 hr; take before intercourse.

Common—headache, dyspepsia, back pain, myalgia, nasal congestion; serious—priapism Caution if sexual activity, exertion risky because of existing cardiovascular disease; caution with alcohol; caution in renal, hepatic impairment; caution in left ventricular (LV) outflow obstruction; caution with potent CYP3 inhibitors; caution in older adults (>65 yr); caution with α-blockers.* Nitrates

Vardenafil (Levitra)

2.5, 5, 10, and 20 mg 4-5 hr

10 mg (5 mg if >65 yr); 1 dose/24 hr; take1 hour before intercourse.

Common—headache, flushing, dyspepsia, rhinitis; serious―priapism Caution in hepatic impairment; caution if sexual activity, exertion risky because of existing cardiovascular disease; caution in LV outflow obstruction; caution with potent CYP3A4 inhibitors; caution in older adults (>65 yr). α-Blockers, nitrates Avoid in patients with prolonged QT taking class IA or III antiarrhythmics.

From Physicians’ Desk Reference, 64th ed. Montvale, NJ, Thompson, 2010. www.pdr.net. *PDE-5 inhibitors should be used with caution in patients taking alpha-adrenergic blockers. This is no longer a contraindication based on labeling, but a number of precautions are based on potential for additive vasodilation in concomitant use: 1. Patients should be on α-blocker therapy and stable before starting PDE-5 inhibitor. 2. Patients who already have hemodynamic instability on α-blockers are at increased risk of additive vasodilatory effects. 3. Use the lowest recommended dose to start. 4. If starting α-blocker in a patient on a PDE-5 inhibitor, use the lowest dose of α-blocker. 5. Other medications or volume status may also contribute to vasodilation and should be considered.

type of incontinence and possible overlap with syndromes such as overactive bladder. Genitourinary and neurologic examinations as well as urinalysis should be performed. A postvoid residual urine measurement is useful for men with obstructive symptoms or patients with voiding difficulty (SIGN, 2004). Urodynamic studies are of uncertain benefit. No studies have shown that these tests improve outcomes or predict who will succeed with surgical treatment (Glazener and Lapitan, 2002; Lemack, 2004). Urodynamics may be helpful if the cause of incontinence is uncertain (Lopez et al., 2002). Children who are thought to be incontinent—that is, those who cannot be categorized as simply enuretic or dysfunctional voiders—need more extensive evaluation. Incontinence treatment should focus on improving quality of life. Stress and urge incontinence may be treated differently, depending on the underlying cause. Physical therapies, medications, alternative treatments, and surgery are options. Pelvic floor exercises are effective and a reasonable first choice for stress and mixed symptoms. It is unknown whether these are effective for urge symptoms (Hay-Smith et al., 2001). Bladder training is effective for urge incontinence (Teunissen et al., 2004). Other options include biofeedback and electrical stimulation (Onwude, 2009). Evidence does not currently support acupuncture treatment (SIGN, 2004). Medications include alpha agonists, anticholinergics, estrogen, serotonin and norepinephrine reuptake inhibitors, 916

and tricyclic antidepressants (TCAs). Oral estrogen replacement therapy should not be used because of the underlying cardiac and cancer risk, as well as the finding that it worsens incontinence (Hendrix et al., 2005). Topical vaginal estrogen appears effective; however, data on long-term use and effects after treatment cessation are limited or lacking. Thus, short-term use is likely most prudent at present (Cody et al., 2009). For stress incontinence, some evidence has shown that α-agonists are more effective than placebo, but the only available form in the United States is pseudoephedrine and side effects limit its use. TCAs are an option, but no randomized controlled trials (RCTs) have evaluated this use (SIGN, 2004). Duloxetine (Cymbalta) improves stress incontinence compared to placebo, but long-term data are lacking (Guay, 2005, Onwude 2009). Anticholinergic drugs such as oxybutynin, tolterodine, solifenacin, and darifenacin are effective for urge incontinence (Table 40-9). Trospium, a quaternary ammonium compound, is also effective (Athanasopoulos and Perimenis, 2009). Preventing incontinence would be ideal. Methods such as pelvic muscle exercises are often recommended for women after childbirth, although evidence on effectiveness is insufficient at present (Hay-Smith et al., 2002). Episiotomy does not appear to reduce urinary incontinency in women (Hartmann et al., 2005).


Table 40-9 Medications for Urinary Incontinence

Medication

Dosage

Stress Incontinence Duloxetine (Cymbalta)*

40 mg twice daily

Pseudoephedrine

30, 60 mg every 4-6 hr 120 mg SR daily

Estrogen*

Topical

Urge Incontinence/Overactive Bladder Tolterodine (Detrol, Detrol LA)

1, 2 mg twice daily 2, 4 mg daily (LA)

Trospium (Sanctura, Sanctura XR)

20 mg twice daily 60 mg daily (XR)

Solifenacin (Vesicare)

5, 10 mg daily

Darifenacin (Enablex)

7.5, 15 mg daily

Oxybutynin (Ditropan, Ditropan XL)

5 mg twice daily 5, 10 mg daily (XL)

Oxybutynin transdermal (Oxytrol)

3.9 mg transdermal patch twice weekly

Oxybutynin transdermal gel (Gelnique)

100 mg/g topical daily

Imipramine (Tofranil)*

10, 25, 50 mg at bedtime; max dose 150 mg

Modified from Athanasopoulos A, Perimenis P. Pharmacotherapy of urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2009;20:475-482; and Physicians’ Desk Reference, 64th ed. Montvale, NJ, Thompson, 2010. www.pdr.net. *Non–FDA-approved use. SR, Sustained release.

Interstitial Cystitis Interstitial cystitis is a chronic, noninfectious bladder disorder predominantly diagnosed in women. Symptoms mimic those of a UTI (urgency, frequency) with the addition of chronic pelvic pain, dyspareunia, or both and varying with bladder filling. Although not associated with cellular change, epithelial inflammation and prolonged symptoms can lead to epithelial damage (Kahn et al., 2005). Two forms are identified: “classic” interstitial cystitis, demonstrating inflammatory bladder wall changes identifiable on cystoscopy, and painful bladder syndrome, defined by the symptoms of interstitial cystitis in the absence of any objective cystoscopic findings (Marinkovic et al., 2009). The main impact of interstitial cystitis is on quality of life. Patients often express somatization and depression or anxiety; as with other somatic pain syndromes, its pathogenesis is unclear. Differential diagnosis includes other somatic syndromes such as fibromyalgia, irritable bowel, and chronic pelvic pain, as well as UTI, overactive bladder, uterine fibroids, and endometriosis. Interstitial cystitis should be considered in any patient presenting frequently with UTI symptoms. There may also be association with autoimmune disorders.

Pentosan polysulfate sodium (Elmiron), 100 mg three times daily, is the only FDA-approved medication for interstitial cystitis. Adjunctive medications include antihistamines, TCAs, gabapentin, anticholinergics, prednisone, and cyclosporine (Marinkovic et al., 2009). Urologic consultation should be considered. Physical therapy, counseling, and bladder training may help (Kahn et al., 2005). Many dietary avoidance recommendations have focused on acidic, highpotassium foods and drinks with acid, caffeine, or alcohol. However, prospective data on dietary interventions are lacking, so such restrictions should be individualized to each patient.

Overactive Bladder Overactive bladder describes a clinical syndrome characterized by lower urinary tract voiding dysfunction. The International Continence Society has defined overactive bladder as “urgency, with or without urge incontinence, usually with frequency and nocturia” (Wein and Rovner, 2002). The lack of specificity inherent in this definition creates potential for overlap with other urinary tract symptom complexes (e.g., LUTS) and diseases. The pathogenesis is uncertain, and urinary tract abnormalities that could cause symptoms should be ruled out. The primary dysfunction revolves around improper detrusor muscle activity and functional reductions in bladder volume. However, the definition does not exclude patients with the symptoms who do not have objective bladder hypercontractility. Furthermore, voluntary control of bladder contraction may be impaired so that the urge to void cannot be controlled (Herbison et al., 2003). Neurologic conditions may contribute. For example, patients with multiple sclerosis, stroke, or diabetic neuropathy might manifest overactive bladder. This might be better described as neurogenic detrusor overactivity, whereas patients without cause or contributor might be described as having idiopathic detrusor overactivity (Herbison et al., 2003). Thus, overactive bladder is best viewed as a descriptive, symptomdriven complex rather than a disease. Overactive bladder affects approximately 16% of adults, with equal gender distribution. However, women are more likely to experience urge incontinence as a feature (Stewart et al., 2003). Patients may plan their days around issues such as restroom access or avoiding social settings because of incontinence. Patients may be reluctant to discuss these symptoms because of embarrassment, so family physicians may not detect the true impact of these symptoms without specific inquiry. Many pharmacotherapy options are available for overactive bladder (see Table 40-9). Bladder retraining is another option. There are no systematic reviews comparing these treatments, although incontinence data have suggested that physical therapies are a reasonable option. There are no important differences in effectiveness among medications. Systematic review of anticholinergic medications versus placebo shows statistically significant effectiveness. However, the clinical significance is uncertain, with the exception of side effects, and long-term treatment effects are unknown (Herbison et al., 2003). Anticholinergic treatment will likely result in one less leakage or voiding episode every 48 hours, but one third of patients experience dry mouth (Hay-Smith et al., 2005b). 917

40


Renal Calculi Adults Approximately 5% to 12% of adults will have a kidney stone, and the chance of a recurrent stone is 50% (Parmar, 2004; Teichman, 2004). Whites have the highest risk, particularly men. Family history increases the risk threefold and is present in 55% of recurrent stone formers (Teichman, 2004). A classic history suggesting renal calculi is the abrupt onset of unilateral flank pain. It often radiates into the groin and may be accompanied by nausea and vomiting. Patients with kidney stones typically have great difficulty finding a comfortable position. On examination, there may be costovertebral angle or lower abdominal pain, and hematuria occurs in 90% of patients (Teichman, 2004). Patients may experience UTI symptoms such as dysuria, frequency, and urgency as the stone passes from the ureter into the bladder. However, patients with fever, microscopic signs of infection, or signs of systemic sepsis may have superimposed UTI. Complete obstruction and hydronephrosis can result in renal failure. Helical non-contrast-enhanced CT is the test of choice for diagnosing renal calculi (Lindbloom and Meadows, 2001). Renal ultrasound and IV urography may be helpful for radiopaque stones and pregnant women (ultrasound only) (Sheafor et al., 2000). Stones larger than 5 mm found in the proximal ureter on more than one imaging study will probably need urology consultation and intervention (Grossfeld et al., 2001b). Stones smaller than 5 mm will likely pass without intervention (Teichman, 2004). Treatment initially focuses on analgesia and relieving nausea and vomiting. Pain results from ureteral obstruction and renal capsular distention and/or hydronephrosis. Pain can be effectively managed with narcotic analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs; ketorolac, indomethacin). Ketorolac (Toradol) is more effective than meperidine (Demerol) and probably as effective as narcotics (Larkin et al., 1999; Teichman, 2004). Alpha blockers such as terazosin or tamsulosin appear to increase the likelihood of a stone passing (DasGupta et al., 2009). Two thirds of stones pass spontaneously. Stones that have not passed within 4 weeks are unlikely to pass (Teichman, 2004). Urine straining is important because a captured stone can be analyzed for content. Repeat imaging is needed when stone passage has not occurred or is uncertain. It is debatable whether all patients should receive an evaluation for metabolic disorders after a first kidney stone. A reasonable workup includes an electrolyte panel, urinalysis, blood urea nitrogen (BUN), creatinine, calcium, parathyroid hormone (if calcium elevated), and stone analysis, if possible. Calcium oxalate is found in 60% to 80% of stones (Parmar, 2004). Patients with recurrent stones need a more extensive evaluation, including urine culture and a 24-hour urine study to determine calcium, oxalate, uric acid, citrate, phosphate, sodium, and creatinine levels (Teichman, 2004). Proper hydration is essential in preventing stones. Patients should aim for urine output of 2 to 3 L/day (Parmar, 2004). Cost-effectiveness data suggest that dietary intervention is appropriate for first episodes (Lotan et al., 2004). Patients with recurrent stones need dietary intervention, a metabolic evaluation, and potassium citrate measurement. Hypercalciuria is an indication for prophylaxis with thiazide diuretics, which effectively reduce recurrence of calcium oxalate 918

stones. Evidence is less clear for other treatments, such as citrate (Pearle et al., 1999). Men with recurrent stones and idiopathic hypercalciuria will have fewer stones on a lowsodium, low-protein diet than men on a low-calcium diet (NNT = 5.5 for 5 years). Low-calcium diets do not reduce stone formation (Borghi et al., 2002). Patients with uric acid stones respond to urinary alkalinization with potassium citrate (Teichman, 2004).

Children Although usually considered an adult problem, children are not immune to urolithiasis. Older children present with typical symptoms, and younger children may have signs mimicking those of colic. About 15% of children presenting to the emergency department who were ultimately diagnosed with urolithiasis by CT did not have hematuria (Persaud et al., 2009). Metabolic disorders are often the cause of pediatric stones, most often hypercalciuria (Peitrow et al., 2002). The mainstay of treatment is a high fluid intake. Urinary alkalinization inhibits cystine and uric acid stones. For calcium-based stones, a diet low in sodium and oxalate and high in potassium is recommended. Excess intake of vitamins D and C is discouraged. Thiazide diuretics are also a treatment option. Gated and ungated shock wave lithotripsy has been successful treatment in children, with minimal morbidity (Shouman et al., 2009).

KEY TREATMENT Use ACE inhibitors and angiotensin receptor blockers for nephropathy prevention in diabetes (Shlipak, 2009) (SOR: A). Antibiotics are ineffective for chronic nonbacterial prostatitis (category IIIb, IV) (Erickson et al., 2008) (SOR: A). Enuresis alarm helps manage nocturnal enuresis (Kiddoo, 2007) (SOR: A). Pelvic floor muscle exercises are used for stress incontinence (Onwude, 2009) (SOR: B). Duloxetine is effective for stress incontinence (Onwude, 2009) (SOR: A). Anticholinergics (oxybutynin, tolterodine, solifenacin, darifenacin) and trospium are effective for urge incontinence (Athanasopoulos and Perimenis, 2009) (SOR: A). PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) are used for erectile dysfunction (Tharyan and Gopalakrishanan, 2009) (SOR: A).

Infectious Disorders Key Points • N eisseria gonorrhoeae and Chlamydia trachomatis cause most cases of urethritis and typically coexist. • Identifying and treating asymptomatic bacteriuria are only important in pregnant women. • Evaluate for urethritis, prostatitis, or both in men with UTI symptoms. • Women with dysuria and frequency without vaginal symptoms have a 90% chance of UTI. • Both antibiotic prophylaxis and cranberry juice prevent recurrent UTI. • The ideal evaluation of children with UTIs is controversial.


Balanitis Balanitis refers to inflammation of the glans penis (Fig. 40-12). It may occur as a local infectious process, as part of a urethritis syndrome (e.g., Reiter’s syndrome), or as a skin disease (e.g., lichen sclerosis). In uncircumcised men, yeast balanitis may result from poor hygiene. Consideration should be given to dermatologic conditions and immunodeficiency in circumcised men.

Epididymitis Epididymitis (epididymo-orchitis) often presents with testicular pain or swelling. It is usually unilateral, with a palpable, tender epididymis and possibly hydrocele. Risk factors include STI, insertive anal intercourse, invasive urinary tract procedures, and anatomic urinary tract disorders. Anatomic abnormalities are the most likely explanation in children. Epididymitis may occur as an STI in men during insertive anal intercourse or in men older than 35 who have undergone invasive procedures (e.g., cystoscopy). The differential diagnosis includes trauma, infarction, testicular cancer, and testicular torsion. Testicular cancer can be misdiagnosed as epididymitis. Thus, family physicians should emphasize close follow-up. Chlamydia trachomatis and Neisseria gonorrhoeae cause most cases in men younger than 35 and usually coexist with asymptomatic urethritis (CDC, 2006). Other causative organisms include gram-negative enteric bacteria. Fungi and tuberculosis are other possible infectious causes. Treatment includes antibiotics, analgesia, and scrotal elevation. In patients in whom gonorrhea or chlamydia is the likely cause, ceftriaxone (single dose, 250 mg IM) and doxycycline (100 mg twice daily for 10 days) is the treatment of choice. In patients who are allergic to these, or likely to have an enteric organism as the cause, 10 days of treatment with ofloxacin or levofloxacin is appropriate (CDC, 2006; del Rio, 2007).

Prostatitis Prostatitis is a fairly common urinary tract disorder in men (Krieger et al., 2003) (see Table 40-7). Categories I (acute) and II (chronic) prostatitis are treated as infectious disorders.

The four-glass method for diagnosing and localizing prostatitis is often recommended but has not been prospectively validated (Stevermer and Easley, 2000).

Acute Bacterial Prostatitis Acute bacterial prostatitis should be suspected in men presenting with symptoms of UTI. Age and immunodeficiency contribute to men having UTIs, so prostatitis is more likely in otherwise healthy men with these symptoms (Lipsky, 1999). Patients may have UTI symptoms (e.g., dysuria, frequency, urgency) and typically systemic symptoms of acute illness, such as fever, chills, and myalgias. Local discomfort in the form of pelvic or back pain is also typical. Examination reveals a tender, boggy prostate. Most experts have recommended against prostate massage in acute prostatitis because it would be very uncomfortable and theoretically could disseminate the infection (Benway and Moon, 2008; Wagenlehner and Naber, 2003). Urine culture is typically positive for the causative organism. Treatment is empiric pending the results. Depending on the degree of illness, patients may need an IV broad-spectrum penicillin or third-generation cephalosporin, possibly with an aminoglycoside, or a fluoroquinolone (Wagenlehner and Naber, 2003). Less severe cases can be managed with oral antibiotics. Options include fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) (Lipsky, 1999). An alternative when STI is likely is intramuscular (IM) ceftriaxone followed by oral doxycycline. Antibiotic therapy is typically 10 to 14 days, although some recommend 4 weeks because of concerns about antibiotics poorly penetrating prostatic tissue. Obstructive uropathy may result from prostatic enlargement; thus, assessment for this clinically or with postvoid residual assessment should be considered (Benway and Moon, 2008).

Chronic Bacterial Prostatitis Chronic bacterial prostatitis may manifest with irritative voiding symptoms, prostatitic obstruction, or recurrent UTIs (Lipsky, 1999). Patients may have microscopic pyuria but negative cultures. Other symptoms include hemospermia, penile discharge, and systemic symptoms. Longer courses of antibiotics are generally considered standard practice. Options include TMP-SMX and fluoroquinolones for 4 to 6 weeks (Lipsky, 1999). Alpha-adrenergic blockers have limited evidence of benefit when added to antimicrobials for category II prostatitis (Erickson et al., 2008). Patients with recurrent symptoms may need longer antibiotic courses, urologic consultation, or reconsideration of their diagnosis.

Sexually Transmitted Infections Chancroid

Figure 40-12 Circinate balanitis in a patient diagnosed with Reiter’s syndrome (arthritis, conjunctivitis, urethritis). (From the CDC Public Health Image Library image 5806. Courtesy Susan Lindsley and Dr. M. Rein.)

Chancroid is caused by infection with Haemophilus ducreyi. A clinical syndrome of painful genital ulcers and adenopathy (patient does not have syphilis; ulcers are herpes negative) allows for presumptive diagnosis (Fig. 40-13). Many treatment options exist (Table 40-10). 919

40


Gonorrhea and Nongonococcal Urethritis Urethritis may present as a urethral discharge or simply dysuria. Family physicians should suspect urethritis in patients with symptoms of UTI, pyuria, presence of leukocyte esterase, and negative urine culture. N. gonorrhoeae and C. trachomatis are the most important causative organisms. Gonococcal urethritis is typically symptomatic. Chlamydia causes most cases of nongonococcal urethritis (CDC, 2006). Various treatment options exist (see Table 40-10). Fluoroquinolones are no longer recommended as a treatment option due to resistance rates (del Rio et al., 2007). Patients with gonorrhea who are not ruled out for chlamydia should be treated for it because co-infection is common (CDC, 2006).

Herpes Genitalis Herpes simplex virus type 2 (HSV-2) causes most genital herpes infections, although HSV-1 causes 50% of first cases (CDC, 2006). An estimated 20% of those older than 12 years have it, and infection is often asymptomatic (USPSTF, 2005). Symptoms, if present, may present as multiple,

small, painful ulcers or vesicles (Fig. 40-14). Causative virus is prognostically important, so confirmatory testing is recommended. Polymerase chain reaction testing is sensitive, whereas a Tzanck test is not (CDC, 2006). Serologic tests for herpes IgG are available but do not differentiate acute from remote infection. The U.S. Preventive Services Task Force (USPSTF, 2005) recommends against routine screening for HSV in asymptomatic adults because there is no evidence that this decreases disease transmission or reduces morbidity. Antiviral medications can treat acute outbreaks and be used as prophylaxis to prevent recurrent outbreaks.

Human Papillomavirus Human papillomavirus (HPV) may cause symptomatic genital warts, although most patients do not manifest them. HPV types 6 and 11 cause most visible warts (CDC, 2006). Certain HPV types are associated with genital squamous neoplasia. Patients with penile plaques suspicious for warts can be examined by placing an acetic acid solution on the plaque and looking for an acetowhite change. Untreated warts will regress, remain stable, or spread. Symptomatic relief is the main treatment goal. Treatment options include podofilox 0.5%, imiquimod (1%, 5%), topical interferon, cryotherapy, office-based chemical treatments (acetic acid), or surgery (Buck, 2007; CDC, 2006,).

Syphilis

Figure 40-13 Chancroid: penile lesions and inguinal adenopathy. (From the CDC Public Health Image Library image 4419. Courtesy Pledger.)

Primary Treponema pallidum infection manifests as a painless genital ulcer known as a chancre (Fig. 40-15). Diagnosis is typically confirmed with a combination of nontreponemal screening tests (rapid plasma reagin [RPR], Venereal Disease Research Laboratories [VDRL]) and a treponema-specific test (fluorescent treponemal antibody absorption [FTA-ABS]). T. pallidum is difficult to culture, so darkfield microscopy or fluorescent antibody testing of a tissue specimen provides definitive diagnosis. Primary syphilis is treated with a single dose of penicillin, 2.4 million units IM in adults and 50,000 to 2.4 million U/kg IM in children) (CDC, 2006).

Table 40-10 Treatment for Selected Sexually Transmitted Infections (STIs)

STI

Medication

Dose

Route*

Duration

Chancroid

Azithromycin

1000 mg

PO

Single dose

Ceftriaxone

250 mg

IM

Single dose

Ciprofloxacin

500 mg

PO

Twice daily for 3 days

Erythromycin base

500 mg

PO

Three times daily for 7 days

Azithromycin

1000 mg

PO

Single dose

Doxycycline

100 mg

PO

Twice daily 7 days

Cefixime

400 mg

PO

Single dose

Ceftriaxone

125 mg

IM

Single dose

Penicillin

2.4 million U

IM

Single dose

Chlamydia

Gonorrhea

Syphilis, primary *PO,

920

Oral; IM, Intramuscular.


Doxycycline and tetracycline are alternatives for penicillinallergic patients.

and microscopy are not accurate enough tests to predict this condition.

Urinary Tract Infections

Uncomplicated Cystitis

Urinary tract infections are the most common urologic issue encountered by family physicians and one of the most common diagnoses overall (Stange et al., 1998). Most are uncomplicated lower UTIs, such as cystitis.

Most UTIs manifest as acute uncomplicated bacterial cystitis, and women experience most of these episodes. Escherichia coli causes up to 90% of cases, with the rest probably caused by Staphylococcus saprophyticus. Other causative organisms include Proteus mirabilis, enterococci, and Klebsiella (Fihn, 2003). To have “uncomplicated cystitis,” women must have no underlying urinary tract abnormalities or immune compromise (Bent et al., 2002). Dysuria, frequency, and urgency are the classic clinical triad. The condition most commonly mimicking UTI is vaginitis. Other conditions have been described (see Dysuria). Patients may also experience back or flank pain and suprapubic abdominal pain. Dipstick urinalysis may show leukocyte esterase or nitrite or may be heme positive. Microscopic analysis should assess for pyuria, hematuria, and bacteriuria. The gold standard for diagnosis is urine culture. Women presenting with at least one UTI symptom have a 50% chance of having a UTI. The combination of dysuria and frequency without vaginal symptoms increases the chance to 90% (likelihood ratio, 24.6). Four symptoms significantly increase the chance of UTI—dysuria, frequency, hematuria, and back pain (Bent et al., 2002). Nitrite-positive or leukocyte esterase–positive dipsticks are the most accurate tests, but cannot rule out a UTI. Antibiotics are the mainstay of treatment, usually for 3 days (Table 40-11). A shorter duration is as effective as longer therapy for most women, including older adult women (Lutters and Vogt, 2002; Milo et al., 2005). In the southeastern and southwestern United States, there is growing E. coli resistance to TMP-SMX, leading some to recommend that this should no longer be first-line treatment for UTI. However, many women treated with TMP-SMX who have a resistant organism on culture achieve clinical cure (Fihn, 2003). Compared with quinolones’ propensity for resistance, TMPSMX is still a reasonable first choice for many patients, and family physicians should base treatment choices on documented local resistance patterns. If resistance to TMP-SMX exceeds 20%, an alternative treatment should be employed (Nicolle, 2008).

Asymptomatic Bacteriuria Approximately 5% of reproductive-age women have asymptomatic bacteriuria (Bent et al., 2002). It is also common in older adults. This is important for understanding the community risk of UTI when evaluating a patient with UTI symptoms. However, although asymptomatic bacteriuria may conceptually place a patient at risk for UTI, identification and treatment do not appear to affect morbidity or mortality (Gartlehner et al., 2004; Lin and Fajardo, 2008). Thus, bacteriuria screening is not recommended (USPSTF, 2008a). In contrast, pregnant women do benefit from screening. Testing with urine culture should be done in all pregnant women at 12 to 16 weeks of gestation (USPSTF, 2008a). Urine culture is the best method, because dipstick testing

Figure 40-14 Crusted lesions of genital herpes on penile shaft. (From CDC Public Health Image Library image 6480. Courtesy Susan Lindsley.)

Complicated Infection

Figure 40-15 Chancre of primary syphilis. (From CDC Public Health Image Library image 6803. Courtesy Dr. M. Rein.)

Complicated UTIs are characterized by signs and symptoms of upper tract (i.e., renal) involvement or by factors that predispose to upper tract involvement. UTIs with signs of renal or systemic involvement are also called pyelonephritis. Most cases of pyelonephritis are caused by ascending bacterial infection from the bladder (Ramakrishnan and Scheid, 2005). Symptoms include fever, flank pain, nausea, vomiting, and costovertebral angle tenderness. Findings such as pyuria are typical, and urine culture is usually positive. White cell casts may be present on urine microscopy. Hospitalized patients with UTIs are best managed based on culture results. E. coli is the typical pathogen for uncomplicated outpatient UTIs and pyelonephritis. E. coli is still the most common isolate in hospitalized patients, but now to a lesser extent, as 921

40


Table 40-11 Treatment Options for Acute Uncomplicated UTIs

Table 40-12 Antibiotics for Uncomplicated UTI Prophylaxis

Medication

Dose

Regimen

Duration

Drug

Pediatric Dose

Adult Dose*

Trimethoprim/ sulfamethoxazole (Bactrim DS, Cotrim DS, Septra DS)

160/800 mg

Twice daily

3 days

Amoxicillin

10 mg/kg, once daily

N/A

TMP-SMX

2 mg/kg, once daily based on TMP

Single strength (80/400 mg), half-tablet at night or three times weekly

Trimethoprim (Primsol)

100 mg

Twice daily

3 days

Trimethoprim

N/A

100 mg nightly

Nitrofurantoin macrocrystals (Macrodantin)

50 or 100 mg

4 times daily

7 days

Nitrofurantoin

1-2mg/kg, once daily

50 or 100 mg nightly

Norfloxacin

N/A

200 mg nightly

Nitrofurantoin monohydrate macrocrystals (Macrobid)

100 mg

Twice daily

7 days

Ciprofloxacin (Cipro)

250 mg

Twice daily

3 days

Gatifloxacin (Tequin)

400 mg

Daily

1 single dose or 3 days

Lomefloxacin (Maxaquin)

400 mg

Twice daily

3 day

Levofloxacin (Levaquin)

250 mg

Once daily

3 days

Norfloxacin (Noroxin)

400 mg

Twice daily

3 day

Fosfomycin (Monurol)

3g

Single dose

Single dose

From Fihn SD. Acute uncomplicated urinary tract infection in women. N Engl J Med 2003;349:259-266. UTIs, Urinary tract infections; DS, double strength.

Enterococcus, Pseudomonas, and Staphylococcus species become more likely (Graham and Galloway, 2001; Scholes et al., 2005). Blood cultures do not necessarily change management (Ramakrishnan and Scheid, 2005). Imaging, such as renal ultrasonography, is sometimes recommended, but it also does not necessarily change management and thus can be employed at clinical discretion (Nicolle, 2008). Outpatients can be managed with an oral fluoroquinolone. Hospitalized patients should receive a fluoroquinolone, an aminoglycoside with or without ampicillin, or an extendedspectrum cephalosporin with or without an aminoglycoside. Patients with cultures showing gram-positive cocci should receive ampicillin-sulbactam with or without an aminoglycoside (Warren et al., 1999). Treatment for 7 to 14 days is usually adequate. Resistant bacteria and renal calculi are the most common causes of treatment failure (Ramakrishnan and Scheid, 2005).

Recurrent Infections Recurrent UTI can be defined as three episodes in 1 year or two episodes in 6 months (Sen, 2008). Self-diagnosis has an 84% PPV in women with recurrent UTIs (Bent et al., 2002). Cultures are helpful in guiding antibiotic choice (Table 40-12). Prophylactic antibiotics are effective for the subset of women with recurrent symptomatic UTI, although choice of patient and duration is uncertain. Because sexual activity 922

Postcoital prophylaxis options: TMP-SMX, nitrofurantoin, fluoroquinolones. TMP-SMX, Trimethoprim-sulfamethoxazole; N/A, not applicable.

is associated with developing UTIs, many physicians recommend that women void immediately after intercourse. However, the poor-quality study examining this practice found no significant effect (Beisel et al., 2002). Thus, no evidence supports recommending this practice to patients. In contrast, postcoital antibiotic prophylaxis reduces the incidence of cystitis (Sen, 2008). Furthermore, it may be as effective as continuous prophylaxis at reducing recurrence, because women in one RCT comparing these methods showed no difference in UTI rates (Albert et al., 2004). In postmenopausal women, topical estrogen is often proposed, but this too lacks good supporting evidence (Sen, 2008). Cranberry juice has potential as a preventive treatment for recurrent UTI. Its effect is likely caused by chemicals that inhibit bacterial adherence to uroepithelial cells rather than urinary acidification (Raz et al., 2004). RCTs support its use in community-dwelling women. Ingesting pure cranberry juice, from 200 mL daily to 250 mL three times daily, or taking cranberry concentrate tablets (1:30) resulted in a 12% to 20% absolute reduction in symptomatic UTIs (NNT = 58). The type of juice is likely a factor, although type and amount have yet to be well defined (Jepson and Craig, 2008; Sen, 2008).

Urinary Tract Infections in Children An estimated 3% to 8% of girls and 1% to 2% of boys will have a UTI (Foxman, 2002; Hellstrom et al., 1991). Pyelonephritis is a clinical diagnosis and is the most common documented serious bacterial infection in febrile infants. Cystitis is common in school-age children and adolescents and, as a general rule, is not a condition of infants or pre–toilet-trained toddlers. Risk factors for UTI range from constipation and dysfunctional voiding to congenital uropathies. Presenting symptoms vary with age and site of infection and may be nonspecific in younger children. Pyelonephritis in infants, for example, may present with fever, irritability, vomiting, diarrhea, poor feeding, or failure to thrive. School-age children and adolescents may present with fever, vomiting and flank pain. Symptoms of cystitis are more common after age 2 years and may include dysuria, frequency, urgency, and low-grade fever (5 WBCs/hpf) and a positive Gram stain are helpful in making the decision to initiate early antibiotic therapy, pending culture results. Treatment remains somewhat controversial, particularly the choice between parenteral and oral antibiotics in the setting of pyelonephritis. For children with pyelonephritis, therapeutic goals include treating or preventing systemic complications of bacteremia, preventing renal sequelae, and ameliorating acute symptoms. Historically, parenteral antibiotics have been the preferred option, particularly in younger children with pyelonephritis. This remains true for infants younger than 4 weeks, who should be hospitalized and receive parenteral therapy. This is also true for older infants and children assessed at high risk because of a septic appearance, vomiting or inability to take oral fluids and medications, dehydration, or concerns regarding compliance. Choice of parenteral antibiotic includes ampicillin in combination with gentamicin or cefotaxime for neonates and third-generation cephalosporin alone for older children. In these cases, transition to oral therapy follows once culture results and sensitivities are known and signs of systemic infection have resolved. Follow-up urine cultures to test for cure are unnecessary in patients with good clinical response (AAP, 1999). Prolonged parenteral therapy is indicated for septic infants. For children 1 month and older not assessed as high risk, it now appears that oral antibiotics are equally effective not only regarding course of illness but also in preventing renal scarring (Montini et al., 2007). Options for initial oral therapy would include amoxicillin– clavulanic acid, TMP-SMX (>2 months), and cephalosporins. Because of the increasing incidence of UTI with ampicillinresistant E. coli, amoxicillin is no longer the preferred initial choice. The recommended length of therapy is typically 7 to 10 days for an uncomplicated UTI (i.e., cystitis) and 10 to 14 days for pyelonephritis (Larcombe, 2007). The most appropriate evaluation after first UTI is controversial (Layton, 2003). Traditionally, children have undergone a complete evaluation for underlying urologic abnormalities that would increase the risk of further infections and renal scarring. This includes renal ultrasound and VCUG. In 309 children younger than 24 months with their first febrile UTI, ultrasound was of limited value because it did not change management, and other tests may be obviated by routine cultures for children with a febrile illness after a prior UTI (Hoberman et al., 2003). However, 29% of 390 children under age 5 years with a first-time febrile UTI had abnormal renal ultrasound findings (Huang et al., 2008). The most common uropathy associated with pediatric UTI is vesicoureteral reflux (VUR), occurring in 30% to 40% of cases. Reflux is diagnosed by VCUG and graded on a scale of 1 to 5, with grade 5 being the most severe. The degree of VUR is directly proportional to the incidence of renal scarring. In addition to the standard fluoroscopic VCUG, radionuclide cystography may be performed. This test has the advantage of less radiation exposure but is lacking in anatomic detail

and is most often used for follow-up studies. The traditional approach to the patient with VUR has been prophylactic antibiotics, with surgical intervention reserved for complicated patients with breakthrough UTIs and evidence of renal injury (see Table 40-12). “Deflux” is a newer, less invasive procedure performed using cystoscopy and is proving to be highly effective in the treatment of reflux. However, the management of VUR is a rapidly evolving field and remains controversial. Evidence supporting prolonged antibiotic prophylaxis is weak because of a lack of properly designed RCTs (Williams et al., 2005). Also, evidence that surgical repair reduces negative outcomes in children with normal renal function is weak or absent (Larcombe, 2007). The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) is a multicenter, randomized, double-blind prospective study currently in progress in the United States designed to assess the efficacy of prophylactic antibiotics in the treatment of grade 1 to 4 VUR in children age 2 months to 6 years. If emerging evidence supports withholding antibiotic prophylaxis, the need for routine VCUG will be obviated. Renal scintigraphy (dimercaptosuccinic acid [DMSA] scan) has been recommended to help diagnose pyelonephritis. This is also controversial because false-negative results could lead to undertreating children with pyelonephritis. DMSA scanning has shown promise in predicting higher grades of reflux in older infants and children (Lee et al., 2009), but this has not been true in neonates (Siomou et al., 2009). DMSA scans are not recommended routinely in children with UTI (AAP, 1999). The prudent course with evaluation is to await more evidence-based management guidelines, which appear to be forthcoming. The ultimate goal in the approach to patients with UTI is to prevent morbidity. Renal scarring may ultimately manifest as hypertension, proteinuria, or both. The incidence of renal scarring in patients with UTI is increased in children younger than 3 years, presence of VUR proportional to grade of reflux, recurrent UTI, and delayed or inadequate therapy.

KEY TREATMENT Continuous or postcoital antibiotics are equally effective for recurrent UTI (Sen, 2008) (SOR: A). Ceftriaxone and cefixime are used for gonorrhea (CDC, 2006) (SOR: C). Fluoroquinolones should not be used to treat gonorrhea (CDC, 2006; del Rio, 2007) (SOR: C). Treat for chlamydia and gonorrhea if treating urethritis presumptively (CDC, 2006) (SOR: C).

Neoplastic Disorders Key Points • B enign prostatic hyperplasia affects most men by age 80 years. Lower urinary tract symptoms vary and may not correlate with prostate size. Other factors such as detrusor dysfunction contribute to LUTS. • Alpha-adrenergic antagonists and 5α-reductase inhibitors are effective for BPH and LUTS. • Smoking is the top risk factor for bladder cancer, and hematuria is the most common presenting sign. 923

40


• P rostate cancer is the most common cancer in men and second most common cause of male cancer death. • There is no PSA value that is both sensitive and specific for prostate cancer. • When ordering a PSA test, family physicians should discuss the risk, benefits, and uncertainties with patients and make a shared decision about whether to screen. • The value of testicular self-examination is unknown.

Benign Neoplasia: Benign Prostatic Hyperplasia Benign prostatic hyperplasia is a common problem for men. More than 50% of men older than 60 years have BPH, and this reaches 80% by 80 years of age (Dull et al., 2002; Thorpe and Neal, 2003). The exact pathogenesis of BPH is uncertain, but it is characterized by epithelial and stromal cell proliferation in the periurethral prostate tissue. The LUTS syndrome (see earlier) overlaps with BPH because up to 30% of men have lower urinary tract symptoms (Thorpe and Neal, 2003). The symptoms defining LUTS were once thought to be solely indicative of BPH. However, LUTS may arise from other disorders (e.g., detrusor dysfunction), and there is a lack of symptomatic correlation with prostate size. However, outflow obstruction from an enlarged prostate may contribute to the development of detrusor dysfunction and urinary retention, referred to as LUTS-BPH. Diagnosis focuses on patient history, rectal examination, and impact on quality of life. Symptoms can vary over time, even without treatment; however, the course is typically progressive, and 1% to 2% of men with BPH experience acute urinary retention annually (Webber, 2006).Various measures exist for measuring symptom severity. The most widely used and well validated is the International Prostate Symptom Score. This scoring system can discriminate the severity of symptoms and treatment response. However, it does not correlate with anatomic findings or objective measures of urinary flow (Barry and O’Leary, 1995). Prostate-specific antigen (PSA) values may increase with prostate hyperplasia, but the overlap with prostate cancer makes this of limited use in managing BPH (Barry, 2001). Medical therapies have overtaken surgical as the most common treatments. Alpha-adrenergic blocking drugs improve urinary symptoms in BPH (Wilt et al., 2008). Alpha-adrenergic antagonists block adrenoreceptors in the prostate and bladder neck (Table 40-13). They may also induce prostate epithelial apoptosis (Thorpe and Neal, 2003). Side effects, particularly blood pressure effects, are important, because these drugs will most often be used in older adults (Schulman, 2003). The α-blocker tamsulosin has recently been implicated in association with serious postoperative ocular complications in patients undergoing cataract surgery (Bell et al., 2009). Prostate tissue is androgen responsive throughout life. 5α-Reductase inhibitors inhibit the conversion of testosterone to dihydrotestosterone, leading to glandular atrophy and reduced prostate volume (20%-30%) (Thorpe and Neal, 2003). It takes many months for these medicines to become effective. Sexual side effects are the most prominent. These drugs also reduce PSA by up to 50%. Based on the Prostate Cancer Prevention Trial, family physicians should discuss potential benefits and harms of 5α-reductase inhibitors (see Prostate Cancer) when using these medications for BPH and LUTS (Kramer et al., 2009). Prostate enlargement can progress 924

Table 40-13 Pharmacotherapy for Benign Prostatic Hyperplasia

Drug

Dosage

Adverse Effects

Alpha-Adrenergic Blockers Alfuzosin (Uroxatral)

10 mg daily

Doxazosin (Cardura, generic)

1-8 mg daily

Terazosin (Hytrin, generic)

1-10 mg at bedtime

Tamsulosin (Flomax)* †

0.4 mg daily

Cardiovascular: dizziness, postural hypotension, syncope Sexual: ejaculatory dysfunction Systemic: asthenia, drowsiness, fatigue, headache

5α-Reductase Inhibitors Dutasteride (Avodart)

0.5 mg daily

Finasteride (Proscar)

5 mg daily

Sexual: impotence, decreased libido, ejaculatory dysfunction

From Schulman CC: Lower urinary tract symptoms/benign prostatic hyperplasia: Minimizing morbidity caused by treatment. Urology 2003;62:24-33; Schwinn DA, Price DT, Narayan P: α1-Adrenoreceptor subtype selectivity and lower urinary tract symptoms. Mayo Clin Proc 2004;79:1423-1434; and Thorpe A, Neal D: Benign prostatic hyperplasia. Lancet 2003;361:1359-1367. *Alpha-1 adrenoreceptor selective. †Associated with postoperative complications from cataract surgery.

enough to obstruct the bladder outlet completely, leading to acute urinary retention. If this occurs, catheterization is warranted. The addition of an α-blocker may aid in voiding once the catheter is removed (Thorpe and Neal, 2003). A randomized, double-blind trial of doxazosin and finasteride over 4 years showed that combining these two medications significantly slowed symptomatic progression and reduced the risk of urinary retention and invasive treatment. Treatment was safe, and the effect of combined treatment on symptom scores was greater than the effect of either agent alone (McConnell et al., 2003). In addition to prescription medicines, a number of alternative therapies are available. Saw palmetto extract (Serenoa repens) is one of the most studied herbal medicines (Buck, 2004). Earlier studies found it is as effective as tamsulosin or finasteride for BPH. Other herbal medicines include β-sitosterols (promising), pygeum (African plum, Prunus africanus), and rye grass pollen (cernilton), with efficacy of the latter two uncertain (Webber, 2006).

Malignant Neoplasias With the exception of prostate cancer, urologic malignancy is relatively uncommon in the general population. After prostate cancer, which is the most common cancer diagnosed in men, the next most common cancers are bladder and renal cell cancers (American Cancer Society, 2009). Testicular cancer is relatively common in young men compared with other cancers in that age group.

Bladder Cancer Bladder cancer occurs in approximately 38.4 per 100,000 men and 9.8 per 100,000 women. Its incidence in white men is twofold higher than in black men (ACS, 2009). The


i ncidence increases with age, with 80% of new cases occurring in patients older than 60 (National Cancer Institute, 2009a). Cigarette smoking is the most prominent risk factor, increasing the risk fourfold to sevenfold. Aminobiphenyl is a cigarette carcinogen linked to bladder cancer. Smoking cessation decreases risk, although it still remains twofold higher 10 years after cessation. Other risk factors include exposure to the aromatic amines used in the dye and rubber industry, benzidine production, dry cleaning, garment manufacturing, and rope and twine manufacturing, as well as exposure to gases and soot from coal. Medical risks include cyclophosphamide, radiation, and prolonged exposure to foreign bodies (e.g., catheter). Finally, aristolochic acid, found in certain weight loss supplements and traditional Chinese herbal compounds containing Aristolochia fangchi, may increase risk. Banned in many western countries, this is still available in the United States (NCI, 2009a). Hematuria is the most common sign of bladder cancer (NCI, 2009a), and diagnosis is most often made by direct bladder visualization (cystoscopy) and biopsy. Positive urine cytology is essentially diagnostic, although false-negative results limit the usefulness of this approach alone. No imaging test can reliably detect bladder cancers. The USPSTF (2004a) recommends against routine screening of asymptomatic persons for bladder cancer. The prevalence of bladder cancer is low, and most patients with hematuria do not have bladder tumors. Most positive screening tests yield false-positive results, prompting unnecessary evaluation.

Penile Cancers Penile cancers are rare; with 1250 new U.S. cases in 2010 (ACS, 2010). Penile cancers are most often squamous cell, and there may be a connection to HPV infection. As expected from this cell type, lesions may appear as a superficial plaque or ulcer. Biopsy or consultation is appropriate in the evaluation of a suspicious penile lesion.

Prostate Cancer Prostate cancer is the most common cancer diagnosed in men and is the second most common cause of cancer death in men after lung cancer. The gap between the annual numbers of diagnoses (217,730) and deaths (32,050) is wide (ACS, 2010). Major risk factors include age, African American race, and family history. Most cases occur in men older than 65. African Americans have a 60% higher incidence compared with whites and experience a disproportionate share of prostate cancer deaths (Harris and Lohr, 2002). Dietary factors may play a role, including the proandrogenic effects of dietary fat, carcinogenic compounds in grilled meats, and antioxidants in vegetables (Nelson et al., 2003). Dietary antioxidants such as lycopene show epidemiologic links (mostly related to tomato consumption) supporting a preventive effect, with possible mechanisms including androgen inhibition (Wertz et al., 2004). However, an RCT using vitamin E and selenium, alone or in combination, failed to show any preventive effect. Given these results and prior disappointing results of other antioxidant trials, clinicians should not recommend supplements for prostate cancer prevention (Lippman et al., 2009).

Prostate cancer is most often indolent, with symptoms typically arising later in the disease course. Physical examination is most often unrevealing. A firm nodule on DRE may indicate a tumor. However, DRE accuracy depends on the performing physician and is imprecise. An abnormal DRE predicts prostate cancer in 18% to 28% of cases (Schwartz et al., 2005). Further, up to 25% of biopsy-detected cancers after an abnormal DRE occur on the side opposite the palpated nodule (McNaughton-Collins et al., 1997). Tumors are most often diagnosed after biopsy for an abnormal screening result. The Gleason score grades cellular differentiation of the two most common patterns seen in a biopsy specimen. Scores range from 2 to 10, with higher scores indicating a more poorly differentiated tumor (Schwartz, 2005). The risk of prostate cancer death is higher with poorly differentiated cancer. Men with low Gleason scores (2 to 4) have a low risk of death, whereas those with higher scores (8 to 10) had a high probability of dying from prostate cancer within 10 years (Albertson et al., 2005). Treatment options for prostate cancer include watchful waiting, brachytherapy, external beam radiation, radical prostatectomy, androgen ablation, and combinations of these options. High-grade tumors receive aggressive treatment, but the ideal treatment for intermediate-grade tumors (Gleason score of 5 to 7) is controversial. Low-grade tumors are candidates for watchful waiting. Treatment for localized disease, regardless of method, carries the risk of persistent negative effects on quality of life, such as sexual, urinary, and bowel dysfunction (Smith et al., 2009). An RCT of prostatectomy versus watchful waiting for low-grade tumors in Scandinavian men found little difference in outcomes during early follow-up, but at 10 years, the prostatectomy group had a lower risk of metastasis or progression and a slightly lower overall mortality (Bill-Axelson et al., 2005; Holmberg et al., 2002). Prostate-specific antigen is a glycoprotein produced by prostatic epithelial cells. Its level increases with prostate adenocarcinoma, hyperplasia, inflammation, procedures, ejaculation, and massage. However, clinical DRE should not affect the PSA level (Barry, 2001). The most widely accepted upper limit of normal for total PSA is 4.0 ng/mL. The Prostate Cancer Prevention Trial, using a biopsy standard, indicated that as PSA levels increase, sensitivity declines and specificity increases, and at no point is there a good balance between the two. Thus, cancer appears ubiquitous—men with normal-range PSA levels may have prostate cancer; 15% of men with a PSA less than 4.0 ng/mL have cancer, 15% of which are high-grade tumors (Thompson et al., 2004). Furthermore, although some studies have concluded that a lower abnormal PSA cutoff level would detect more cancer (Punglia et al., 2003), these findings indicate that more men would have unnecessary biopsies. Thus, PSA testing suffers from both a high false-positive rate and false negatives as (Harvey et al., 2009). It is unknown whether PSA screening reduces all-cause mortality. Two large, randomized screening trials, the Prostate, Lung, Colorectal, and Ovary (PLCO) trial, and the European Randomized Study of Screening for Prostate Cancer (ERSPC), were initiated to evaluate the impact of screening on mortality. The ERSPC study did show a 20% reduction in prostate cancer death; 1410 men would need to be screened and 48 prostate cancer cases treated to prevent 925

40


one death in 10 years. Overdiagnosis of clinically insignificant prostate cancer was a problem (Schroder et al., 2009). In contrast, interim reports from the ongoing PLCO trial found no differences in prostate cancer mortality between the test and control groups (Andriole et al., 2009). Should screening prove beneficial, African American men and patients with first-degree family histories (age 2.5 ng/mL should be screened every year. ○ PSA > 4.0 ng/mL should be referred for biopsy. Consider individual risk for prostate cancer in men with PSA between 2.5 and 4.0 ng/mL. Does not support routine testing. Offer PSA testing and DRE annually beginning at age 50 years for men with at least 10-year remaining life expectancy as part of risk/benefit discussion; African Americans, and those with family history in one or more first-degree relatives diagnosed at an early age, should begin at 45 years. American Academy of Family Physicians Recommends against screening men 75 and older. American Urological Association Offer DRE and PSA testing to asymptomatic men 40 years or older with remaining life expectancy more than 10 years. Modified from American Academy of Family Physicians. Recommendations for clinical preventive services; American Cancer Society guideline for early detection of cancer; American Urological Association. Prostate-specific antigen: best practice statement: 2009 update; US Preventive Services Task Force. Screening for prostate cancer: recommendation statement. Ann Intern Med 2008;149:185-191. DRE, Digital rectal examination; PSA, prostate-specific antigen.

Renal Cancers Renal cancers are twice as common in men as in women; more than 57,000 cases are diagnosed annually in men (ACS, 2010). Risk factors are less well understood than for other urologic cancers. Heavy tobacco use (>20 packs/year) is a risk factor in men, and severe obesity is a risk in both genders. Risks from occupational or medication exposure are less certain (Dhote et al., 2004). Diagnosis of renal cancer is often incidental to an imaging study (e.g., ultrasound) obtained for another reason. Hematuria is also a clinical sign that may lead to the diagnosis. Although renal cell cancers are curable if localized (88%100%), overall survival rates (40%-60% at 5 years) are not as encouraging as in other urologic cancers (Dhote et al., 2004; NCI, 2009d).

Testicular Cancer Approximately 8400 men were diagnosed with testicular cancer in 2010 (ACS, 2010). It is unusual in that it occurs mostly in young men (15-35 years) and is the most common


cancer in this group. Orchiopexy in children with cryptorchidism does not necessarily prevent cancer, so these patients should be followed closely (NCI, 2009e). Most testicular tumors are initially discovered by patients. Typical presentations include painless testicular lumps or scrotal pain, edema, or hardness. Symptoms can mimic those of epididymitis, and tumor should be in the differential of this condition (Kinkade, 1999). Ultrasound is the initial study of choice for suspected testicular masses. Most tumors are germ cell neoplasms. Thus, serum tumor markers (β-hCG, lactate dehydrogenase, alpha-fetoprotein) are important in the diagnosis, prognosis, and monitoring aspects of care. However, normal values do not rule out cancer in patients with a mass, and they are not appropriate as screening tools, so they should not be used to decide whether a confirmed mass is cancerous (Kinkade, 1999). Patients are typically followed for many years for treatment failure or recurrence, and family physicians play an important role in ensuring that patients participate adequately with follow-up. Testicular self-examination or clinical examination might detect cancer at an earlier stage but is highly unlikely to have a significant impact on testicular cancer mortality, with

s urvival rates already so high. Thus, USPSTF (2004b) does not recommend testicular cancer screening in the general population.

Wilms’ Tumor Wilms’ tumor presents in childhood as an abdominal mass. It is a rare cancer, with approximately 500 cases annually. Wilms’ tumor has good cure potential, with survival rates greater than 90% at 4 years (NCI, 2009f).

KEY TREATMENT Use of 5α-reductase inhibitors is effective for benign prostatic hyperplasia (BPH) (Kramer et al., 2009; Thorpe and Neal, 2003) (SOR: A). Alpha-adrenergic blockers are also used to treat BPH (Wilt et al., 2000) (SOR: A). 5α-Reductase inhibitors are used for prostate cancer prevention (SOR: B). Surgical treatments may be needed for BPH (SOR: A).


Web Resources www.aafp.org/online/en/home/clinical/exam/p-t.html. American Academy of Family Physicians; recommendations for clinical preventive services. www.cancer.org/docroot/PED/content/PED American Cancer Society; guidelines for early cancer detection. www.cdc.gov/STD/treatment/default.htm Centers for Disease Control and Prevention; guidelines for treating sexually transmitted infections. http://phil.cdc.gov/phil CDC Public Health Image Library. http://nkdep.nih.gov/professionals/index.htm National Kidney Disease Education Program site on chronic kidney disease with guidelines and GFR calculators for adults and children. www.cpcn.org/ipss.pdf International Prostate Symptom Score.

www.cancer.gov/ National Cancer Institute main site, with information on various cancers and treatment. www.auanet.org/ American Urological Association; guidelines and patient education resources. http://www2.niddk.nih.gov/NR/rdonlyres/93B6388F-B429-46039C3C-6765BDEB49A1/0/NIHCPSIEnglish.pdf National Institutes of Health Chronic Prostatitis Symptom Index. www.kidney.org/professionals/kdoqi/guidelines_ckd/p9_approach.htm. National Kidney Foundation/Kidney Disease Quality Initiative; clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

927

41 CHAP T E R Ophthalmology Earl R. Crouch, Jr., Eric R. Crouch, and Thomas R. Grant, Jr.

Chapter contents Red Eye Evaluation Red Eye in Infants Red Eye in Adults and Older Children

Ocular Trauma and Other Emergencies Emergencies Urgent Situations

Pediatric Ophthalmology Evaluation of Vision within First 4 Months of Life Vision Screening and Ocular Examination Testing Visual Acuity

928 928 930 932

936 936 936

939 939 940 940

Patients present to the family physician with a limited set of symptoms, often with subtle differences to indicate mild or serious ocular conditions. To decide when to treat patients and when to refer them to an ophthalmologist, the family physician must possess a complete appreciation of these subtle differences. Knowledge of the basic anatomy of the eye is essential in determining these diagnostic differences (Fig. 41-1).

Red Eye The family physician frequently encounters patients who complain of a “red eye.” Usually, the condition causing the red eye is a simple disorder, such as conjunctivitis or subconjunctival hemorrhage. These conditions improve spontaneously or are readily treated. A red eye, however, may be a symptom of a more serious disorder, such as herpetic dendritic ulcer, iritis, acute angle-closure glaucoma, ophthalmia neonatorum, or congenital glaucoma. These conditions must be clearly distinguished from the much more common conjunctivitis and subconjunctival hemorrhage because immediate referral to the ophthalmologist is paramount. To evaluate the red eye, the family physician needs to have available a penlight, magnifying glasses, visual acuity chart, fluorescein dye, anesthetic drops, and tonometer.

Evaluation

Strabismus and Amblyopia Refractive Errors and Color Vision Headaches Learning Disabilities and the Eye Pediatric Cataracts Retinoblastoma

Adult Ophthalmology Correction of Refractive Errors Ocular Medications Ophthalmic Conditions in Older Adults

941 943 944 945 945 946

947 947 948 948

body, such as a grain of sand, lodged in the conjunctival sac produces a rapid hyperemia, whereas a viral or allergic conjunctivitis, or an iritis, generally produces a slowly progressive redness. Ocular pain is an important symptom (Table 41-1). Irritation of the superficial layer of the cornea, as caused by a small foreign body, is accompanied by a superficial “grain of sand” sensation in the eye. Deeper inflammatory processes, such as iritis or iridocyclitis, or a deeper penetrating foreign body in the cornea, present with more severe, dull pain in the eye. Abnormal light sensitivity (photophobia) is a third danger symptom that must be elicited by the family physician. Photophobia occurs with corneal inflammation, iritis, and angle-closure glaucoma. Patients who have conjunctivitis usually do not have abnormal light sensitivity (Box 41-1). Patients who complain of a red eye often complain of discharge from the eye (Table 41-2). If they do not complain of eye discharge spontaneously, the physician must inquire about the presence, type, and quantity of discharge. Purulent (creamy white or yellow watery) discharge suggests a bacterial cause. A serous or clear discharge suggests a viral cause. Scanty, white, stringy exudate occurs most often with allergic conjunctivitis. The absence of discharge indicates an unusual cause for red eye, such as iridocyclitis, ultraviolet (UV) light keratitis (snow blindness), or acute angle-closure glaucoma. A complaint of diminished visual acuity is a serious danger sign and must be elicited in the history.

Symptoms and Signs

Physical Examination

Patients who complain of a red eye generally can tell the physician whether the eye irritation occurred rapidly or progressed slowly. This information is important because a small foreign

It is important to examine both eyes because many patients with conjunctivitis in one eye have clear signs of early conjunctivitis in the other. The type of infection must be closely

©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10041-5

Ophthalmology Optic axis

Visual axis Anterior chamber

Cornea Iris

Posterior chamber

Canal of Schlemm or sinus venosus

Ciliary process

Conjunctiva bulbi Ciliary muscle

Zonule of Zinn

Pars ciliaris retinae

Lens

Ora serrata Equator Pars optica retinae

Vitreous Choroidea Sclera

Optic papilla Optic cup

Fovea centralis Sheath Optic nerve

Central artery Figure 41-1 Anatomy of the right eyeball. (From Scheie HG, Albert DM. Textbook of Ophthalmology, 9th ed. Philadelphia, Saunders, 1977.)

Table 41-1 Red Eye: Differential Diagnosis

Parameter

Conjunctivitis, Bacterial

Iritis

Keratitis

Acute Glaucoma

Vision

Normal

Blurred

Blurred

Marked blurring

Pain

None

Moderately severe; intermittent stabbing

Sharp, severe

Severe; sometimes nausea/ vomiting

Photophobia

None

Moderate

Moderate

Moderate

Discharge

Usually significant with crusting of lashes

None

None to mild

None

Conjunctival injection

Diffuse

Circumcorneal

Circumcorneal

Diffuse

Appearance of cornea

Clear

Clear

Cloudy

Cloudy

Pupil size

Normal

Constricted

Normal

Dilated

Intraocular pressure*

Normal

Normal or low

Normal

Elevated

From American Academy of Ophthalmology. The Red Eye. AAO Professional Information Committee, San Francisco, 1986. *Caution: Do not measure IOP with discharge present.

inspected; conjunctival infection is characterized by individually visible vessels in the conjunctiva branching from the sclera toward the cornea, whereas ciliary infection appears as a red ring surrounding the cornea in which individual vessels are not clearly visible. The significance of ciliary infection is that the deep ciliary vessels are involved, indicating a much more serious inflammatory condition of the eye, such as a deep corneal infection, iritis, or iridocyclitis. Inspect the palpebral conjunctiva carefully with magnification to determine whether lymphoid hyperplasia (cobblestone appearance) exists. The type and quantity of discharge are assessed by pulling down the lower lid. The appearance of the punctum should be examined to determine whether pus is coming out

of the tear duct. Palpation of the tear sac on the upper portion of the nose (lacrimal crest) demonstrates tenderness in cases of acute dacryocystitis. Carefully examine the cornea. Normally, the cornea is perfectly transparent. Excessive fluid within the stroma of the cornea results in partial opacification that can be observed by direct illumination with a penlight. A diffuse corneal haze can occur with congenital glaucoma and angle-closure glaucoma. After inspection with a penlight under magnification, perform corneal staining with fluorescein using sterile filter paper strips. The stained part of the strip is moistened with water and touched to the conjunctiva away from the cornea. With blinking, the fluorescein 929

41

Ophthalmology

Box 41-1 Approach to Patient Presenting with Red Eye (No History of Trauma) 1. 2. 3.

heck for the following symptoms or signs. C a. Reduced vision b. Pain c. Photophobia d. Corneal staining e. Corneal edema f. Unequal pupils g. Elevated intraocular pressure Refer to ophthalmologist if any of these signals are present. If none of the above is present, the diagnosis is probably conjunctivitis. 4. The triad of a red eye, pain, and loss of vision should always alert the examiner to a potentially blinding condition.

Table 41-2 Conjunctivitis Clues

Finding

Cause

Purulent discharge

Bacterial

Serous or clear discharge

Viral

Stringy, white discharge

Allergic

Preauricular lymph node enlargement

Viral

Preauricular lymph node enlargement is a frequent sign of viral conjunctivitis and usually is not present with acute bacterial conjunctivitis (see Table 41-2).

Red Eye in Infants Key Points • R ed eye in infants requires special attention to differentiate ophthalmia neonatorum, congenital glaucoma, conjunctivitis, and dacryocystitis. • Cultures should be obtained in neonates with symptoms suggestive of ophthalmia neonatorum. • Febrile children with acute dacryocystitis should have cultures tested to direct management. • Infants with symptoms of congenital glaucoma should be promptly referred to an ophthalmologist. • For chronic dacryocystitis, the best age for surgical intervention is 6 to 12 months. • Infants with a dacryocystocele require prompt ophthalmologist referral and systemic antibiotics.

Several conditions occur specifically during the first year of life. They include ophthalmia neonatorum, acute and chronic dacryocystitis, bacterial conjunctivitis, and congenital glaucoma.

Ophthalmia Neonatorum spreads over the cornea. A UV light source enhances fluorescence. Areas of bright-green staining denote absent or diseased epithelium. Corneal staining readily demonstrates a corneal abrasion and helps identify corneal foreign bodies and infectious epithelial defects, such as herpetic dendritic keratitis (Fig. 41-2). Examine the pupils carefully for size and shape. In most people the pupils are of equal size; a small percentage have congenital variation in the size of the pupils (anisocoria). These patients are often aware that their pupils are unequal. In patients with previously equal pupils, inequality of the pupil may indicate iritis, typically with the affected pupil partially constricted. In acute angle-closure glaucoma the pupil is usually partially dilated and may not be round. Unequal pupil size is an important sign of significant ocular trauma or third nerve palsies. Estimate the anterior chamber depth by side illumination with a penlight. If the anterior chamber is normal or deep, the entire surface of the iris is well illuminated. When the anterior chamber is shallow, the iris on the more distant side of the pupil is in shadow. A shallow anterior chamber in a red eye may indicate acute angle-closure glaucoma or ocular trauma. The anterior chamber appears deep in patients with congenital glaucoma. If the red eye does not have an obvious infection, measure the intraocular pressure (IOP) with a tonometer. IOP is normal in most patients with red eye, except for those with acute angle-closure glaucoma. With iritis and traumatic, perforating ocular injuries, IOP is generally low. Sterilize the tonometer before and after application to a red eye, preferably by heat sterilization. 930

Ophthalmia neonatorum is an infection or inflammation of the conjunctiva that occurs during the first 4 weeks of life. Possible causes include chemical conjunctivitis, Neisseria gonorrhoeae, and chlamydial infection. The increased incidence of venereal disease and shortcomings in silver nitrate prophylaxis are significant factors in the constantly evolving clinical picture. Ophthalmia neonatorum frequently is a manifestation of a systemic infection, requiring determination of the exact cause in all but the most transient cases. Table 41-3 outlines the management of the various types of ophthalmia neonatorum. At present, erythromycin is the medication of choice. Povidone-iodine ophthalmic solution (0.5%) is less toxic, inexpensive, and effective, but is not generally used because of confusion over povidone solution versus povidone soap. Silver nitrate has been replaced by erythromycin, so the incidence of chemical conjunctivitis has decreased significantly. Before the neonatal prophylaxis, gonorrhea was a common cause of ophthalmia neonatorum. Half of patients with gonococcal conjunctivitis develop corneal clouding, a major cause of blindness. Gonococcal conjunctivitis still occurs, despite erythromycin prophylaxis. Frequently, the infant with gonococcal conjunctivitis presents with swollen lids, purulent exudates, beefy-red conjunctiva, and conjunctival edema. The gonococcal organism can rapidly penetrate the intact corneal epithelium and produce corneal perforation if recognition and treatment are delayed. When gonococcal conjunctivitis is suspected, referral to an ophthalmologist is critical. Patients may also have systemic involvement, with associated central nervous system (CNS) signs. Both parents should be examined for venereal disease and treated, if necessary.

Ophthalmology

Figure 41-2 Corneal abrasion. The patient had a fingernail injury caused by the daughter (left). Characteristic fluorescein staining is displayed in the adjacent photomicrograph (right).

Table 41-3 Management of Ophthalmia Neonatorum

Disease

Diagnosis

Treatment

Gonococcal conjunctivitis

Gram-negative intracellular diplococci plus Growth on chocolate agar or Thayer-Martin agar plus Fermentation glucose negative and maltose negative

Ceftriaxone, 125 mg IM single dose plus one of the following: Oral tetracycline, 500 mg qid Oral doxycycline, 100 mg bid Oral erythromycin, 500 mg qid Ophthalmology consultation

Other bacterial conjunctivitis

Gram stain plus Growth on blood agar or chocolate agar

Gram positive: erythromycin ointment qid, or fluoroquinolone qid, for 2 wk Gram negative: gentamicin, tobramycin, or fluoroquinolone, qid for 2 wk

Chlamydial conjunctivitis

Giemsa stain— basophilic intracytoplasmic inclusion bodies plus Chlamydial culture

Tetracycline, 500 mg qid for 3-4 wk Erythromycin, 250-500 mg for 3 wk Doxycycline, 100 mg bid for 2 wk Azithromycin, 1 g (one dose)

IM, Intramuscularly; bid, twice daily; qid, four times daily.

A recommended regimen for ophthalmia neonatorum prophylaxis is a single application of silver nitrate 1% aqueous solution, erythromycin 0.5% ophthalmic ointment, or tetracycline 1% ophthalmic ointment (CDC, 2002b).

Chlamydial Infection Chlamydial infections are a leading cause of ophthalmia neonatorum. There is a high incidence of this type of infection because of the frequent exposure to the newborn during delivery and the lack of effective prophylaxis. The onset of infection can occur at any time. The typical picture is a mild unilateral or bilateral mucopurulent conjunctivitis with moderate

lid edema, chemosis, and conjunctival injection. Systemic involvement may include rhinitis, vaginitis, and otitis media. Treatment is with tetracycline ointment or erythromycin four times daily for 4 weeks. In addition, both parents should be treated with oral tetracycline or azithromycin. Alternative treatments include oral erythromycin or doxycycline for 3 weeks. Systemic tetracycline should be avoided in breastfeeding women with this infection. Conjunctival cultures are indicated in all cases of suspected infectious neonatal conjunctivitis (CDC, 2002).

Bacterial Conjunctivitis The most common gram-positive bacteria that are causative agents of conjunctivitis include Staphylococcus aureus, Streptococcus pneumoniae, and group A and B streptococci (Fig. 41-3). Gram-negative organisms include Haemophilus influenzae, Escherichia coli, and Pseudomonas aeruginosa. Bacterial conjunctivitis can occur at any age from the first day of life. Chemosis (edema of bulbar conjunctiva), purulent discharge, lid edema, and injection are common signs. Associated systemic septicemia can occur, especially with Pseudomonas infection. Cultures should be prepared on blood and chocolate agar. A topical fluoroquinolone often provides effective treatment for severe cases before culture results (Leibowitz, 1991). Gram-negative organisms are best treated with tobramycin or a topical fluoroquinolone. Systemic antibiotics are recommended when there is evidence of systemic disease. Physicians should use caution with gentamicin, neomycin, and sulfacetamide eye medications, because these drugs may cause a toxic chemical conjunctivitis and complicate management. Patients with mild conjunctivitis generally respond to erythromycin or bacitracin ointment.

Acute Dacryocystitis Neonates may present with acute dacryocystitis, an inflammation of the lacrimal sac (Fig. 41-4). Pain, tearing, redness, and discharge usually occur. If the child is febrile, culture testing and Gram staining should be done. S. pneumoniae and S. aureus are the most common pathogens. Systemic antibiotics are indicated for the acute stage. The ophthalmologist should be consulted immediately, because irrigation and probing may be necessary to establish drainage as quickly as possible. Severe cases may progress to a dacryocystocele, sepsis, meningitis, or even death, especially in young infants. 931

41

Ophthalmology

Figure 41-5 Congenital glaucoma in a 2-month-old infant who presented with a cloudy cornea involving the right eye. Intraocular pressure was elevated. The diagnosis was congenital glaucoma.

Figure 41-3 Purulent conjunctivitis may indicate infection with Staphylococcus, Haemophilus influenzae, Streptococcus, or Pseudomonas. (From American Academy of Ophthalmology. The Red Eye. San Francisco, AAO Professional Information Committee, 1986 [AAO. The Red Eye].)

blinking or lid spasm (blepharospasm). An enlarged cornea or corneal clouding can be detected clinically and measured with a plastic ruler (normal, ≤12 mm) (Fig. 41-5). Corneal edema is the result of elevated IOP, which causes breaks in the inner corneal layers (Descemet’s membrane) and intrusion of anterior chamber fluid into the corneal stroma. Increased IOP causes significant optic nerve damage, which can lead to blindness. Whenever glaucoma is suspected, immediate consultation is indicated. Surgical treatment of congenital glaucoma is successful in approximately 90% of cases. These patients must be followed by an ophthalmologist for life as a precaution against recurrent IOP elevation and amblyopia.

KEY TREATMENT Figure 41-4 Acute dacryocystitis in a neonate with fever and malaise. Lacrimal sac massage and systemic antibiotics relieved the acute infection.

Chronic Dacryocystitis and Nasolacrimal Duct Obstruction Infants with chronic dacryocystitis usually present to the physician with a chronic history of tearing and crusting with a chronic yellow discharge. Topical antibiotics, such as a fluoroquinolone four times daily, should be used. The mother should be taught to compress or massage the lacrimal sac four to six times daily. Approximately 80% of these inflammations resolve spontaneously by age 6 to 12 months. If treatment is not successful or if dacryocystitis persists, the patient should be referred and the nasolacrimal duct system irrigated between 6 and 10 months of age. Before age 14 months, a single probing is curative in about 90% of cases.

Newborns should be prophylactically treated with erythromycin 0.5% or tetracycline 1% ophthalmic ointment to reduce the risk of ophthalmia neonatorum (CDC, 2002) (SOR: A). Ciprofloxacin 0.3% ophthalmic solution is effective empiric treatment of bacterial conjunctivitis (Leibowitz, 1991) (SOR: A). A broad-spectrum antibiotic for 5 to 7 days is generally effective for most cases of bacterial conjunctivitis (American Academy of Ophthalmology [AAO], 2008) (SOR: A). Children with nasolacrimal duct obstruction may undergo naso lacrimal duct surgery between 6 and 12 months of age, or sooner if clinically indicated (Katowitz et al., 1987) (SOR: C). Children with congenital glaucoma should be promptly referred to a pediatric ophthalmologist or glaucoma specialist (AAO, 2008) (SOR: A).

Red Eye in Adults and Older Children Key Points

Congenital Glaucoma Congenital glaucoma is a potentially blinding condition with an incidence of 1 per 10,000 births. It is often confused with chronic dacryocystitis. About two thirds of these cases are bilateral. These patients, similar to those with dacryocystitis, present with excessive tearing. The infants usually are light sensitive (photophobic) and frequently bury their head in a pillow or blanket. These infants often have intense 932

• R ed eye in adults and older children requires careful evaluation to differentiate the various causes of inflammation. • Purulent conjunctival discharge warrants culturing and broadspectrum antibiotics. • Allergic conjunctivitis generally responds well to topical treatment; symptoms may manifest or worsen on initiation of systemic antihistamines.

Ophthalmology

Figure 41-6 Seborrheic blepharitis is characterized by greasy, dandruff-like scales on the lashes. (From AAO. The Red Eye.)

Figure 41-8 Chalazion of right upper eyelid in 10-year-old girl. (From AAO. The Red Eye.)

Treatment of both these conditions is long and laborious. Lid hygiene is recommended for both conditions. Topical antibiotics are prescribed for staphylococcal blepharitis. Both conditions are recurrent and require repeated therapy.

Stye Figure 41-7 Acute hordeolum, or stye. The swollen, tender, red eyelid includes an acute, boil-like lesion. Treatment includes warm compresses and topical antibiotics. (From AAO. The Red Eye.)

• O rbital cellulitis requires prompt computed tomography and systemic antibiotics. Cultures should be obtained from the nasopharynx, conjunctiva, and blood. • Iritis is characterized by pain, photophobia, miosis, and circumciliary injection and generally occurs after blunt trauma. • A red eye in a contact lens wearer requires prompt evaluation for a corneal ulcer. • Acute angle-closure glaucoma is an ocular emergency and requires immediate treatment by an ophthalmologist.

Blepharitis Blepharitis is a chronic lid inflammation that involves abnormalities of the glands surrounding the eyelashes. The two most common types are chronic staphylococcal infections of the lid and seborrheic blepharitis (Fig. 41-6). Staphylococcal blepharitis is the most common inflammation of the external eye. It is frequently asymptomatic initially, but as the disease progresses, the patient complains of foreign body sensation, matting of the lashes, and burning. Lid crusting, discharge, redness, and loss of lashes are observed. Seborrheic blepharitis is associated with seborrhea of the scalp, lashes, eyebrows, and ears, characterized by greasy, dandruff-like scales on the lashes. Blepharitis is not associated with skin ulcerations.

A stye is the most common localized infection of one of the glands of the eyelid margin (Fig. 41-7). It is an acute boil-like lesion, and the patient usually has a swollen, tender, red eyelid. There may be a moderate amount of conjunctival injection. Treatment includes warm compresses for 15 minutes four times per day and topical antibiotics. Systemic antibiotics are usually not indicated unless there is a preseptal cellulitis component. Generally, the stye drains spontaneously within several days. If resolution does not occur within 2 weeks, the patient should be referred.

Chalazion A chalazion is a chronic swelling of the eyelids not associated with conjunctivitis (Fig. 41-8). The chalazion, a granulomatous inflammatory reaction, may persist for weeks or even months. Chalazia are generally not amenable to oral or topical antibiotics, unless the lesion is secondarily infected. Chalazia are usually rubbery, cystic, and nontender on palpation. When the upper lid is involved, vision may be temporarily blurred. If the chalazion persists for more than 4 to 6 weeks, it may require incision and curettage. Recurrent chalazia may be caused by an underlying sebaceous carcinoma, so the lesion should be biopsied and sent for pathologic testing.

Bacterial Conjunctivitis All common bacteria may cause acute conjunctivitis. Presently, S. pneumoniae, H. influenzae, S. aureus, and P. aeruginosa are the most common pathogens. The most frequent 933

41

Ophthalmology

causes of hyperacute conjunctivitis are N. gonorrhoeae and N. meningitidis. Risk factors for bacterial conjunctivitis include contact lens wear, exposure to infectious persons, compromised immune systems, nasolacrimal duct obstruction, and sinusitis. In the presence of a severe purulent discharge, culture of the conjunctiva is mandatory (see Fig. 41-3). Subconjunctival hemorrhage may occur with bacterial conjunctivitis and is especially common with H. influenzae conjunctivitis. Treatment of conjunctivitis is with a topical antibiotic, such as erythromycin or bacitracin. Tobramycin ophthalmic ointment may be used for many gram-positive and gram-negative conjunctivitis cases. Ciprofloxacin and ofloxacin also provide effective broad coverage of most types of conjunctivitis. Gonococcal and Haemophilus conjunctivitis require systemic and topical therapy. If the conjunctivitis does not improve within 2 to 3 days or the worsening symptoms develop, the patient should be referred to an ophthalmologist. Ciprofloxacin and ofloxacin provide effective broad coverage of most causative organisms. Newer fluoroquinolones such as gatifloxacin and moxifloxacin provide more potent coverage and better penetration for gram-positive organisms than earlier types of fluoroquinolones. Topical steroids or antibiotic-steroid combinations for conjunctivitis or other causes of red eye should not be used unless the patient is under the care of an ophthalmologist. Topical corticosteroids have four potentially serious ocular side effects and are contraindicated for conjunctivitis, as follows: 1. Steroids can facilitate penetration of an undetected corneal herpetic infection to the deeper corneal layers and cause corneal perforation. 2. Prolonged local use of the corticosteroids (usually >2 weeks) can cause chronic open-angle glaucoma. 3. Prolonged use of topical corticosteroids can cause cataracts. 4. Topical corticosteroids are capable of potentiating the development of fungal corneal ulcers. In general, topical steroids should be reserved for patients under the care of an ophthalmologist.

KEY TREATMENT Cultures of the conjunctiva are indicated in all cases of suspected infectious neonatal conjunctivitis (AAO, 2003) (SOR: A).

Viral Conjunctivitis Viral conjunctivitis, in contrast to bacterial conjunctivitis, has a less prominent discharge that is usually watery. The condition is highly contagious, and handwashing is important to avoid infection. When infected, hospital personnel, daycare workers, and institutional personnel should avoid contact with others. Palpable preauricular lymph nodes frequently are present with viral conjunctivitis and represent an important sign that can differentiate it from bacterial conjunctivitis. An associated upper respiratory infection may occur. In advanced cases, true photophobia and blurred vision caused by corneal involvement may be present and require consultation. However, most viral conjunctivitis is self-limiting, and no specific treatment is indicated. Topical 934

steroids are contraindicated. Most viral infections resolve within 10 to 14 days, and specific serologic diagnosis is not necessary. If the conjunctivitis persists or there is any pain or change in vision, the patient should be referred.

Allergic Conjunctivitis Allergic conjunctivitis is frequently found in pediatric patients and adults. It is usually seasonal, most often the spring and fall. Although often associated with allergic rhinitis, allergic conjunctivitis may occur without systemic symptoms. There is an increase in itching, redness, and swelling, which is variable from day to day. Seasonal allergic conjunctivitis is related to tree and grass pollens, each of which has a distinct season and severity. The condition may be asymmetric. Chronic allergic conjunctivitis is most often related to various indoor allergens, including dust mites, animal dander, molds, and cockroaches. Cats are especially irritating to the eye for the allergic patient. Treatment for allergic conjunctivitis involves avoidance procedures for outdoor allergens, keeping windows closed at night during allergy season, and eye protection (even sunglasses can reduce exposure to allergens). Washing the face after coming indoors, washing the hair when showering, and keeping the patient’s hands away from the eyes can reduce allergen exposure. Bed linens should be washed weekly. Occasionally, allergy testing and allergy shots may be necessary in severe recalcitrant cases. Symptomatic treatment of allergic conjunctivitis includes cool compresses, artificial tears, and over-the-counter (OTC) antihistamines. Topical antihistamine-decongestant combinations include naphazoline hydrochloride/antazoline phosphate (Vasocon-A) and naphazoline hydrochloride/ pheniramine maleate (Naphcon-A), which are reasonably safe and effective. However, rebound vasodilation can occur and cause chronic hyperemia and conjunctival injection. Cromolyn sodium 4% and olopatadine hydrochloride (Patanol) are effective mast cell stabilizers. Ketorolac tromethamine (Acular), azelastine hydrochloride (Optivar), and lodoxamide tromethamine (Alomide) are also reasonable options for managing allergic conjunctivitis. Systemic allergy medications may cause allergic conjunctivitis to manifest because of reduced tear film production.

Subconjunctival Hemorrhage A patient may present with a bright-red eye, normal vision, and no pain. Usually, no obvious cause exists, but in some patients there is a history of coughing, sneezing, or straining before the hemorrhage is present. The patient should be reassured that it is nothing more than hemorrhage of the conjunctiva. There is no therapy, except reassurance that the blood will clear within 2 to 3 weeks. Hematologic blood coagulation studies are usually of limited value in patients with subconjunctival hemorrhages unless there is a history of recurrence. Additionally, it is unusual for a hemorrhage to involve the relatively avascular sclera. If trauma is suspected, the patient should be referred to an ophthalmologist to rule out more serious injuries, such as perforation, contusion, or occult rupture of the globe. Subconjunctival hemorrhage may indicate that the patient is a battered child or adult, and other signs of bodily trauma should be investigated.

Ophthalmology

Corneal Herpetic Infections Herpetic infections of the eye can produce conjunctivitis, corneal inflammation (keratitis), and uveitis (inflamed iris, ciliary body, and choroid). The herpes simplex virus (HSV) is the most common cause of corneal opacification in temperate-zone countries. The human is the only natural host for this DNA virus. Approximately 90% of the population has systemic antibodies to HSV. The incubation period of HSV infection is 2 to 12 days. HSV type 1 (HSV-1) is the most common cause of ocular infection, but transmission of HSV-2 also can occur. Although classically HSV-1 is the oral type and HSV-2 is the genital type, current epidemiologic studies indicate that either type may be the source of corneal infection, and therefore cultures and viral titers are often sent for both types.

Primary Herpes Simplex Infection Primary ocular infection in a nonimmune subject usually presents as conjunctivitis with a clear watery discharge, skin vesicles on the lids, and preauricular nodes. Associated vesicles and ulcers on the oral mucosa and skin are common. Corneal involvement also may occur with single or multiple dendrites. If dendrites are present, the patient should be referred for treatment. Particular attention should be given to inspecting the nose for possible lesions. A lesion at the tip of the nose indicates involvement of the cornea through the nasociliary branch of cranial nerve V. Treatment generally involves trifluridine 1% (Viroptic) drops five times daily for 10 to 14 days. If other regions are involved, oral acyclovir is added to trifluridine, as in eyelid or corneal involvement. These patients should be managed by an ophthalmologist.

Recurrent Corneal Herpetic Infections At the time of the primary herpetic infection, the virus gains access to the CNS, where it resides in a latent state in the trigeminal and other ganglia. Recurrent attacks occur when the latent state is reversed. The virus travels via the sensory nerves to target tissues, one of which is the eye. Recurrent corneal involvement also includes the development of single or multiple dendritic ulcers. After a brief period, the plaque of epithelial cells desquamates to form a linear branching ulcer (dendrite). When a corneal dendrite is detected by corneal staining with fluorescein, the patient should be referred.

Figure 41-9 Orbital cellulites in 3-year-old patient. (From AAO. The Red Eye.)

e xophthalmos in children. It may be difficult to differentiate a periorbital or anterior lid cellulitis from a true posterior orbital cellulitis. With a true orbital cellulitis, the child or adult has pain on movement of the eye, conjunctival edema, and limited extraocular movements. The most common causative organisms are S. aureus, Streptococcus, and H. influenzae. Cultures should be obtained from the nasopharynx, conjunctiva, and blood. Immediate hospitalization and ophthalmic consultation are necessary. Emergent computed tomography (CT) should be performed to rule out orbital cellulitis. If orbital cellulitis is diagnosed, immediate hospitalization with intravenous (IV) antibiotics and ophthalmologic consultation should be undertaken. Appropriate systemic antibiotic treatment depends on the causative organism. Cavernous sinus thrombosis, meningitis, and blindness are serious complications of orbital cellulitis.

Preseptal Cellulitis

Iritis

Preseptal cellulitis involves the eyelid and periorbital soft tissues and is characterized by acute eyelid erythema and edema. The infection usually occurs in the setting of an upper respiratory tract infection, external ocular infection, or trauma to the eyelids. Patients may have a mild fever and tend to complain of epiphora, conjunctivitis, and localized tenderness. However, the signs of orbital cellulitis are generally absent, unless a preseptal cellulitis evolves into an orbital cellulitis. Treatment is initiated empirically in most cases with cefuroxime, ceftriaxone, or nafcillin.

Iritis is an inflammatory process of the anterior chamber, often associated with blunt trauma or infection. Redness, pain, and photophobia occur with iritis. No discharge is seen, and the pupil is constricted. Circumcorneal (ciliary) injection may occur. IOP is normal or low. Initial treatment may include dilation with homatropine and loteprednol etabonate (Lotemax) for patient comfort, with immediate referral to an ophthalmologist. Consultation should be obtained for all such patients as soon as possible.

Orbital Cellulitis Orbital cellulitis, most frequently caused by an extension of infection from the ethmoid sinus, can occur in adults and children (Fig. 41-9). It is the most common cause of

Corneal Ulcers The most common causes of corneal ulcers include grampositive organisms, such as staphylococci and streptococci; and gram-negative organisms, such as Pseudomonas aeruginosa and Enterobacteriaceae. Less common gram-negative 935

41

Ophthalmology

organisms include Bacteroides. Risk factors for corneal ulcers include patients with corneal erosions, persistent epithelial defects, impaired immunologic mechanisms, contact lenses, chronic topical or systemic steroid use, diabetes, and alcoholism. Corneal ulcers require consultation with an ophthalmologist for appropriate culture and antibiotic therapy.

Angle-Closure Glaucoma Acute elevations in IOP can occur when the outflow of aqueous humor is suddenly blocked. The condition is more common in Asians but may occur in any patient. An acute angle-closure attack may follow an episode of emotional or physical stress, dilation of the pupil in dim lighting, or rarely, after instillation of dilating eyedrops. A patient having an acute attack usually has severe ocular pain, redness, blurred vision, rainbow-colored halos around lights, and sometimes nausea and vomiting. On examination, the eye is usually red, pupil mid-dilated and poorly reactive, and IOP greatly elevated. Generally, only one eye is affected at a time. Corneal clouding or corneal edema may be present in advanced cases. An acute episode of angle-closure glaucoma is an ocular emergency and requires immediate treatment to lower IOP by medical treatment. Once IOP is under control, yttrium-argongarnet (YAG) or argon laser peripheral iridectomy is performed.

the eye because they continue to cause damage long after the initial chemical contact. Corneal melting can lead to perforation, and severe chronic glaucoma can occur as a later complication. Burns of the eye by acids or alkalis are true ocular emergencies. An alkaline substance, such as lye, can cause permanent and irreversible blindness. The immediate treatment of chemical burns must be continual irrigation of the eyes, with up to 1000 mL of normal saline (NS) or lactated Ringer’s (LR) solution. If these solutions are not available, water from a shower, spigot, bathtub, or drinking fountain is appropriate. The conjunctival pH should be assessed after irrigation and again 30 minutes later to confirm stabilization of the ocular surface; pH value should be 7.5 to 8. If the pH remains abnormal, irrigation should be repeated until the pH is normal. Patients are managed with aggressive antibiotic ointment therapy and lubrication following a chemical burn. After the initial ocular irrigation, ophthalmologic consultation must be immediate.

KEY TREATMENT Chemical burns of the ocular surface should be washed with at least 1 liter of fluid and tested until the pH returns to normal. An ophthalmologist should evaluate the affected eye within 24 hours after treatment (AAO, 2007) (SOR: C).

Ocular Trauma and Other Emergencies Key Points

Central Retinal Artery Occlusion

True emergencies can be classified as those for which therapy should be instituted within minutes. Two true emergencies in the eye are chemical burns of the cornea and central retinal artery occlusion.

With an incidence of about 1 in 10,000 people, central retinal artery occlusion is generally not the result of trauma. Risk factors include atrial fibrillation, mitral valve disease, atherosclerosis, a hypercoagulable state, and hypertension. Additionally, prolonged intraorbital swelling can cause occlusion of the central retinal artery. Such situations occur particularly in patients who are having surgery in the face-down position. The characteristic fundus appearance with central retinal artery occlusion is narrow arterioles and a pale optic disc. In addition, there is diffuse retinal whitening. A cherry-red spot occurs only several hours after the initial retinal artery occlusion (Fig. 41-10). Treatment of central retinal artery occlusion must be immediate, including breathing into a small paper bag to help increase the patient’s carbon dioxide level. Emergency paracentesis is a rapid method to decompress the eye and may actually provide immediate restoration of vision. However, most physicians are reluctant to perform paracentesis on a patient within a few minutes. Ocular massage is another means of decompressing the eye. Some centers have hyperbaric oxygen available, which may also be helpful in restoring retinal perfusion for some patients. Treatment should be instituted within 90 minutes if any realistic hope of possible visual recovery can be expected. Patients with central retinal artery occlusion should be thoroughly evaluated for cardiac and carotid disease.

Chemical Burns

Urgent Situations

Most acids produce the extent of their damage immediately on contact—the more concentrated the acid, the more severe the immediate effect. Alkali burns are more devastating to

Urgent situations include those for which therapy should be instituted within minutes or a few hours. They include penetrating injuries of the globe, acute angle-closure glaucoma,

• C hemical burns require immediate evaluation and treatment to stabilize the ocular surface. • Central retinal artery occlusion requires immediate intervention to return oxygenation to the retina. Patients should be thoroughly evaluated to determine the source of the retinal artery occlusion. • Hyphema should be carefully managed with bed rest, shielding the injured eye, and appropriate pharmacologic or surgical treatment to minimize potential complications. Patients with hyphema and angle recession require lifelong evaluation for possible glaucoma. • Ocular foreign bodies of the surface can be conservatively managed with removal of the foreign material and appropriate antibiotic ointment. Care should always be taken to rule out an occult ruptured globe. • The early signs of a retinal detachment include an increase in floaters or flashing lights. Retinal detachments warrant careful evaluation and prompt intervention.

Emergencies

936

Ophthalmology

Figure 41-10 Central retinal artery occlusion of left eye with Hollenhorst plaque in right eye. Patient has a characteristic cherry-red spot involving the macula of left eye (left). Hollenhorst plaque with a retinal arcade in right eye suggests bilateral carotid disease and cardiovascular disease (right).

papillary block, orbital cellulitis, corneal ulcer, corneal foreign body, gonococcal conjunctivitis, ophthalmia neonatorum, and acute iritis. In addition, trauma with retinal tears, vitreous hemorrhage, retinal detachment, and hyphemas constitute urgent situations.

Ocular Foreign Body and Other Eye Injuries The most common eye injury encountered in family practice is a foreign body in the eye. The most common causes of a foreign body in the conjunctival sac or one embedded in the cornea are particles blown in by the wind, occupational or work-related injuries, and metallic foreign bodies that may fly into the eye, such as after a person hits a metal object with a hammer. It is important to evaluate the location of the foreign body and, in the case of corneal foreign bodies, the depth of penetration. Symptoms may be helpful; superficial foreign bodies in the cornea generally present with the complaint of a dust particle in the eye. Foreign bodies that have penetrated deeper into the corneal stroma produce a dull, aching pain perceived in or behind the eye. On examination, it is important to look carefully at the inflammatory response of the eye. A purely localized conjunctival inflammation pattern is generally associated with superficial foreign bodies. Ciliary injection is a warning sign that a deep penetration may have taken place, and an ophthalmologic consultation should be sought immediately. Examine the eye after the instillation of ophthalmic local anesthetic to avoid blepharospasm and evasive eye movements. Inspect the cornea with a penlight or ophthalmoscope in a darkened room. Use of the slit on the ophthalmoscope can help visualize irregularities in the corneal surface. Staining with fluorescein demonstrates abrasions and helps identify otherwise transparent foreign bodies. The family physician may elect to remove a foreign body in the conjunctival sac by irrigation with a sterile solution or after eversion of the upper lid with a moistened cotton swab. In the case of superficial corneal foreign bodies, a physician may attempt to remove it with a moist sterile swab, but embedded foreign bodies should be referred to an ophthalmologist.

Corneal Abrasions Corneal abrasions are often caused by foreign bodies underneath the upper lid or inadvertent injury from a finger or small object. Evert the lid and examine for conjunctival foreign bodies. To evert the lid, the patient is seated and asked to look downward. The upper lid is grasped by its central lashes and pulled downward and slightly outward. The examiner then depresses the upper lid with a cotton applicator proximal to the upper tarsus margin. Gentle pressure is maintained until the upper lid is flipped into the everted position. Frequently, the foreign body is observed and can be removed with a cotton applicator or forceps. Corneal abrasions generally can be treated with an antibiotic ointment. Small abrasions often do not require patching. Large corneal abrasions may require pressure patching or bandage contact lens. If the conjunctival or corneal foreign body is not easily removed with a cotton applicator, the family physician should obtain ophthalmologic consultation. If the abrasion is not healed within 24 hours, an ophthalmic consultation should be obtained. Corneal abrasions should also be carefully inspected for other ocular injury. Any irregularity of the pupil in the presence of a corneal abrasion could signify an underlying occult penetrating injury. In such cases, the patient should be immediately directed to an ophthalmologist for further evaluation.

Contact Lens Overwear Patients suffering from contact lens overwear syndrome have worn their lenses longer than usual and typically awaken during the early-morning hours with severe pain and tearing. In response to prolonged wear, the cornea becomes swollen and develops epithelial defects. Patients need reassurance that the condition is usually not serious, even though the pain is severe. However, occasional contact lens–induced corneal abrasions, especially those associated with soft lenses, can rapidly progress to severe corneal infection. Patients should be seen the next day and referred if they have not improved. Contact lens wear may be resumed only after the corneal epithelium is well healed. 937

41

Ophthalmology

Metallic Foreign Bodies Metallic foreign bodies, if allowed to stay in the eye for a number of hours, frequently leave a “rust ring” that is clearly visible after removal of the foreign body. Rust rings irritate the cornea and result in long-lasting inflammatory changes in the eye. Follow-up should be daily, with staining of the cornea to demonstrate the expected rapid healing. If healing does not take place over 24 to 48 hours, suspect an infection in the corneal stroma and obtain consultation. Topical antibiotic ointments are used after removal of foreign bodies in an attempt to prevent this complication.

Corneal and Scleral Lacerations Corneal and scleral lacerations fall within the realm of the ophthalmologist and should be referred immediately after a shield is placed over the eye. Frequently, signs of corneal and scleral lacerations include unequal pupils, decreased IOP, iris prolapse, and hyphema, and a corneal laceration often also involves the lens. It is important to consider posterior injuries to the globe, including retinal detachment, retinal tear, and vitreous hemorrhage (Fig. 41-11). Patients can often be managed as outpatients with oral antibiotics. Intravitreal antibiotics may be given at ruptured-globe repair. Some patients are hospitalized for IV antibiotics, although current intravitreal penetration of many antibiotics is often comparable. Corneoscleral lacerations should be principally repaired at the presenting institution when possible with available ophthalmology services. Hospital transfers delay wound closure or risk wound extension or prolapse of intraocular contents.

Blunt Eye Injuries Blunt eye injuries are common and may result from relatively trivial injuries or high-velocity impact projectiles. An exact history of the trauma must be obtained to assess the velocity involved, which in turn may indicate the extent of ocular damage. Inquiry must be made to determine whether visual acuity changes occurred immediately after the injury. Flashing lights are often seen at the instant of injury and indicate irritation of the retina, because any message to the brain from the retina is perceived as light. Persistent blurred vision is indicative of a more serious injury. It may indicate blood in the anterior chamber that is suspended in the aqueous humor. Free-floating blood in the anterior chamber is generally not appreciated by direct ophthalmoscopy. A slit-lamp examination is necessary to observe the suspended red blood cells in the anterior chamber.

Black Eye (Eyelid Contusion) A black eye may be serious or relatively minor. If accompanied by severe pain, bleeding, or constant blurred vision, more serious eye trauma must be considered. In such patients, orbital CT scan and ophthalmologic consultation may be necessary to rule out a ruptured globe.

Red Eye Almost all ocular trauma cases include bleeding or dilation of blood vessels on the surface of the eye (subconjunctival hemorrhage). This may be observed with any degree of eye 938

Figure 41-11 Corneal leukoma in 6-year-old boy. Diagnosis was ocular trauma and penetrating corneal laceration.

injury. For example, a subconjunctival hemorrhage may be spontaneous and often indicates minor injury. In the presence of other findings, a subconjunctival hemorrhage suggests more serious injury, particularly if a concomitant hyphema or vitreous hemorrhage is present.

Pupillary Change Blunt trauma to the eye may result in lacerations of the sphincter muscle of the pupil. These are manifested by traumatic mydriasis. Unlike the unequal pupils seen with congenital anisocoria, traumatic mydriasis is characterized by recent onset of unequal pupils and by the irregularity of the dilated pupil. Although traumatic mydriasis by itself is not harmful, it suggests severe blunt trauma and is an indication for a careful assessment of other ocular structures, including the vitreous and retinal periphery.

Traumatic Hyphema Blunt trauma to the eye may cause injury to the iris, angle structures, and other intraocular structures. Hemorrhage into the anterior chamber, or hyphema, is most often found in children. The agent producing the hyphema is usually a projectile that strikes the exposed portion of the eye. A great variety of missiles and objects may be responsible, including balls, rocks, projectile toys, air gun, paint balls, bungee cords, and the human fist. With the increase of child abuse, fists and belts have started to play a prominent role. Boys are involved in 75% of cases. Rarely, spontaneous hyphemas occur and may be confused with traumatic hyphemas. Spontaneous hyphemas are secondary to neovascularization, ocular neoplasms (retinoblastoma), and vascular anomalies (juvenile xanthogranuloma). Vascular tufts that exist at the pupillary border have been implicated in spontaneous hyphema. A traumatic hyphema may be graded by measuring the height of the layered hyphema in the anterior chamber in millimeters. A hyphema is an ocular emergency and should be referred immediately. Cataract, choroidal rupture, vitreous hemorrhage, angle recession glaucoma, and retinal detachment are often associated with traumatic hyphema and compromise the final visual acuity prognosis. It is important to recognize that the prognosis for visual recovery from traumatic hyphema is directly related to three factors: (1) amount of associated damage to other ocular structures (e.g., choroidal rupture or macular scarring), (2) presence or absence of secondary hemorrhage, and (3) presence or absence of complications

Ophthalmology

of glaucoma, corneal blood staining, or optic atrophy. With treatment, most hyphema patients have a good visual outcome. (See the discussion of hyphema grading and complications, as well as treatment and prognosis, online at www.expertconsult.com.)

KEY TREATMENT Hyphemas are generally well managed with bed rest, shielding of the injured eye, and medical control of the hyphema and intraocular pressure (Crouch et al., 2009) (SOR: A). If IOP remains elevated or hyphema occupies more than 50% of the anterior chamber, surgical evacuation of the clot may be required to lower IOP, preserve corneal clarity, and reduce optic atrophy (Sheppard et al., 2009) (SOR: A).

Nonaccidental Inflicted Neurotrauma (Formerly “Shaken Baby Syndrome”) The true incidence of nonaccidental inflicted neurotrauma is unknown because of the difficulty collecting statistical data. An estimated 1300 children in the United States experience fatal head trauma from child abuse annually (JAMA, 2003). The findings of nonaccidental inflicted neurotrauma involve repetitive, violent, unrestrained, acceleration-deceleration, head and neck movements. Neurotrauma can occur without blunt head trauma. Cases primarily occur in children under 3 years old, usually during the first year of life. Typically, patients present with fracture and intracranial or intraocular hemorrhages; not all findings are required to establish the diagnosis. An ophthalmologic consult should be obtained for all patients with suspected nonaccidental inflicted neurotrauma, with carefully documented retinal drawings or preferably fundus photography. Approximately 20% of cases are fatal within the first few days of presentation. Traumatic retinoschisis, if present, is highly specific for nonaccidental inflicted neurotrauma, particularly if the child is younger than 5 years.

Retinal Detachment An increase in previous floaters or the onset of new floaters may occur in a retinal detachment. Traumatic detachment of the retina can be observed after blunt eye injury, especially in older adults. Retinal detachment may also occur spontaneously, especially in patients with high myopia. The patient may complain of reduced overall brightness in the involved eye or may have continuous light flashes, indicating retinal traction. After eye trauma, it is imperative to inspect not only the central portions of the retina, but the peripheral portions as well. This examination should be performed in a darkened room after instillation of a short-acting mydriatic agent. Any questionable findings should be referred to an ophthalmologist immediately. Other serious injuries are traumatic tears of the iris, subluxation or dislocation of the lens that occasionally displaces into the anterior chamber, and blowout fracture of the orbit, with impaired upward eye movement caused by entrapment of the inferior rectus muscle. These injuries are usually readily identified.

Pediatric Ophthalmology Key Points • C hildren should be screened at birth, birth to 3 months, 3 to 6 months, 6 to 12 months, 3 years, 5 years, and then every 1 to 2 years. • Amblyopia and strabismus are distinct but may be associated. Children can have amblyopia without having strabismus. All children with amblyopia or strabismus should be referred to a pediatric ophthalmologist. • Cataracts are an important cause of amblyopia in children and require prompt intervention. • Pediatric cataracts may be a sign of a metabolic disorder, TORCH infection (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex), or chromosomal abnormality. • Leukocoria warrants further investigation; significant causes include cataracts, Toxocara canis infection, retinal disease, and retinoblastoma.

Evaluation of Vision within First 4 Months of Life Parents may report that their baby does not appear to look at them. This statement requires the physician to document a history of prematurity, fetal distress, anoxia, or birth trauma carefully. A failure to reach developmental milestones may indicate neurologic abnormalities. A history of seizure disorder, cerebral palsy, or chromosomal abnormalities helps identify potentially serious causes. In this case, visual acuity or the child’s ability to fixate must be assessed. Normal newborns follow faces. By age 2 or 3 months, infants normally follow light and high-contrast objects. Assessment of vision can be achieved by using an optokinetic nystagmus drum. Oculomotor disturbances may be the underlying cause of the child’s apparent visual inattention. Bilateral cranial nerve III palsy, congenital fibrosis syndrome, or partial cranial nerve III palsy may give this impression as well. Searching or roving eye movements are a form of profound nystagmus, with little foveal perception. Nystagmus is an important sign of decreased vision, indicating visual acuity often in the range of 20/200. The onset is usually at birth or shortly thereafter. The nystagmus can be a jerk or pendular nystagmus. The direction should be characterized as horizontal, vertical, or rotary. Abnormalities of the anterior portion of the eye can cause profound visual loss and are easily visible with a +10 magnification. They include corneal opacities (leucoma) caused by congenital glaucoma, Peter’s anomaly (abnormal cornea and lens), and leukocoria (white pupil) related to congenital cataracts, inflammatory disease, or retinal disease. Evaluation of the posterior aspect of the eye, including examination of the red reflexes, may indicate an early retinal detachment or retinoblastoma. Optic nerve abnormalities may be associated with midline CNS defects, such as an absent septum pellucidum, agenesis of the corpus callosum, or hypopituitarism. Optic nerve abnormalities such as optic nerve hypoplasia are associated with nystagmus. CT or magnetic resonance imaging (MRI) can identify these abnormalities. Electroretinography (ERG) may be 939

41

Ophthalmology

elpful for determining the cause of decreased visual acuity. h An abnormal ERG is seen with Leber’s congenital amaurosis, congenital achromatopsia, and congenital stationary night blindness. Visual-evoked potential testing may be necessary to determine whether vision is intact. Some infants who have a completely normal eye examination but demonstrate poor fixation may actually have a delay in maturation of the visual system. Normally, the initial visual system development matures by 4 to 6 months of age. Visual-evoked potential acuities are about 20/400 during the first few days of life and improve to about 20/40 by 6 months of age. In some patients, visual-evoked responses and clinically assessed visual function may be abnormal, only to improve between 4 and 12 months of age. Although incompletely defined, in delayed visual maturation the vision is decreased, but the ocular examination appears normal, including brisk pupillary response to light. Typically, there is no nystagmus, and ERG is normal.

Table 41-4 Recommended Vision Screening by Family Physicians

Age

Examination

Referral Criteria

Newborn

Penlight examination of cornea Rule out nystagmus Red reflexes

Any ocular pathology Nystagmus Abnormal red reflexes or white reflex

6 months

Fixation to light and small toys Penlight examination Corneal light reflex test, cover test Red reflexes

Object to occlusion Nystagmus; any ocular pathology Strabismus Abnormal red reflexes or white reflex

3 years

Visual acuity: Snellen letters, tumbling E, or HOTV wall chart Corneal light reflex test, cover test Fundus examination

Acuity of 20/40 or less in one or both eyes Strabismus Any ocular pathology

≥5 years

Visual acuity: Snellen letter, tumbling E, or HOTV (see online text) Corneal light reflex test, cover test Fundus examination

Acuity of 20/30 or less in one or both eyes Strabismus Any ocular pathology

Vision Screening and Ocular Examination Appropriate vision screening is one of the most important factors in pediatric eye care. Because focused visual stimuli are critical to normal development, early detection and correction of visual problems reduce serious vision impairment or blindness. The American Academy of Ophthalmology (AAO), American Academy of Pediatrics (AAP), and American Association of Pediatric Ophthalmology and Strabismus (AAPOS) strongly support the goal of early detection and treatment of eye problems in children. In particular, vision screening is needed to detect four major conditions: strabismus, amblyopia, ocular disease, and refractive errors. Family physicians are ideal vision screeners because of their ability to detect abnormalities at an early age. Essential components of vision screening are age, testing format, testing procedures, efficacy, and referral criteria. On a practical level, vision screening must be cost-effective and time-efficient. The testing devices must be readily available and relatively easy to use. High sensitivity is essential to keep overreferrals and underreferrals to a minimum.

Four Stages of Screening The AAO and AAPOS recommend that children be examined for eye problems in the following four stages (Table 41-4): 1. In the newborn nursery, physicians should examine all infants. Ophthalmologists should be consulted to examine patients at high risk for conditions such as retinopathy of prematurity (ROP), cataracts, congenital defects, and other ocular pathology. 2. At 6 months 3. At 3 years 4. At 5 years and older The AAO statement recommends that family physicians establish a close working relationship with a local ophthalmologist who is familiar with children’s eye problems. The collaboration can help clarify questions about vision screening and the need for referral. (See online content for specific information on different stages of vision screening.) Also, special groups may need additional vision screening. The following children should also be screened, even if they are not due to be examined by their age: all children 940

at high risk of having vision disorders, including those who are mentally retarded or who have trisomy 21 or cerebral palsy; and all children who show signs or symptoms of visual problems, experience school failure, or have reading difficulties or other learning problems (e.g., dyslexia). It is important to note that children with learning disabilities such as dyslexia have the same incidence of ocular abnormalities (strabismus, refractive error) as children without such disabilities. Dyslexia involves interpretation by cortical processing centers and does not generally indicate any ocular pathology. Eye defects do not cause letter, number, or word reversal.

Testing Visual Acuity Several diagnostic tests are used to detect strabismus, amblyopia, ocular disease, and refractive errors. These include visual acuity and fixation preference tests, corneal light reflex test, cover test, simultaneous red reflexes test, fundus examination, stereoscopic tests, and photorefractive techniques. The best way to screen for possible visual loss caused by amblyopia is to measure the visual acuity or fixation preference of each eye separately. The covered eye should be firmly occluded during the assessment to avoid any peeking. When there is no apparent sign of amblyopia, the only clue to poor vision may be the child’s objection to having the better eye occluded. Additionally, the child may demonstrate a fixation preference of the better-seeing eye, with an inability to fixate on distance objects in the amblyopic eye. Both are common signs of amblyopia that may be caused by a refractive error, media opacities, retinal or optic nerve abnormality, or cortical processing problem.

Ophthalmology

Equipment required for testing children older than 42 months consists of standard wall charts containing Snellen letters, Snellen numbers, tumbling Es, and HOTV monitors, as well as some means of occluding the nontested eye, ideally, occluder patches (Opticlude, Coverlet).

Stereoscopic and Photorefractive Tests The visual acuity test is the most widely used vision screening test, but use of this test alone will underrefer many patients with amblyopia and undiagnosed strabismus. Stereoscopic tests such as the random dot E stereogram are relatively inexpensive, fairly accurate, and easy to use. Stereopsis tests are complementary and offer additional information regarding a patient’s visual health. The use of photorefractive apparatus is relatively new. Reproducible results of photography of the red reflex can screen the nonverbal infant or child. The sensitivity is high (95%) for refractive error in the range of 1.00 to 2.00 diopters. A problem with this technique is that cycloplegia is usually required to prevent obtaining false-positive results, especially for myopia. In addition, two photographs are needed to avoid missing an astigmatic refractive error. The technology offers great promise, but it must be cost-effective. As newer, more rapid and accurate vision tests are developed, these may be incorporated into the screening process.

Strabismus and Amblyopia Strabismus and amblyopia are two of the most common visual problems affecting children. Strabismus occurs in 4% and amblyopia in 4% of the population. Half of all amblyopia patients have a concomitant strabismus. Conversely, half of all amblyopia patients will have no demonstrable strabismus. Movements of the eyes horizontally and vertically are controlled by the six muscles attached to the sclera of each eye. Movement of both eyes in unison allows vision of singular images. Through a blending process called fusion, the brain combines the two images into a single, three-dimensional image. As long as the eye muscles are able to work together, the brain can process incoming visual information. When the eye muscles are not coordinated, one eye deviates inward, outward, or upward, and the other eye remains straight. When this occurs, the brain receives a different image from each eye and cannot combine the two disparate images into a single image frame. Misalignment of the eye muscles results in strabismus. In addition to a breakdown or absence of fusion, the causes of strabismus may include refractive errors, anatomic anomalies, and abnormal tonic innervation. Adults with acquired strabismus frequently develop double vision, but children with strabismus quickly learn to ignore or suppress the image seen by the deviated eye. As a result of suppression, the straight eye takes over most of the work of seeing, and the crossed eye develops reduced central vision because of lack of use. There are various types of strabismus and may be horizontal, vertical, or rotational (cyclotorsional). (See online text for additional information on specific types of strabismus.) Loss of vision in a relatively normal eye is called amblyopia. The phrase “lazy eye” should not be used in diagnosing patients because it can be confused with amblyopia and strabismus. As mentioned earlier, these two distinct clinical entities

Figure 41-12 Amblyopia. This 5-year-old patient also required patching of the better-seeing eye to improve vision in the amblyopic eye.

are associated with each other in only 50% of cases. In children younger than 4 years, amblyopia is the most frequent cause of unilateral vision loss (Fig. 41-12). The condition is usually unilateral, although bilateral high myopia, hyperopia, or astigmatism may occur. Unless treatment begins early, loss of vision in the affected eye may be permanent. Amblyopia is usually treatable if detected at age 3 to 4 years but is generally considered irreversible after 13 years; however, treating amblyopia in patients older than 13 years has had some success. The earlier treatment begins, the better the prognosis for the patient. The primary treatment of amblyopia includes the use of patches, glasses, or both. The better eye is occluded, and underlying conditions such as cataracts or refractive errors are treated.

Testing for Strabismus The corneal light reflex test, cover test, red reflex, and extraocular rotations are four basic tests for strabismus. To perform the corneal light test, project a penlight onto the cornea of both eyes simultaneously while the child looks straight ahead. Compare the placement of the two corneal reflections. When the eyes are straight, the light appears at the same point on each cornea. If a muscle deviation is present, the reflected light appears slightly off center in one eye. Figure 41-13 illustrates the placement of corneal reflections as they would appear for each direction of deviation. In part A, note that the light is centered on the cornea of the left eye but is displaced laterally, or outward, on the right cornea, indicating that the right eye is turned inward, or is esotropic. In B, note that the light is centered again on the left cornea but is displaced medially, or inward, on the right cornea, demonstrating an outward-turning, exotropia of the right eye. In part C the light indicates that the right eye is turned upward, or is hypertropic, and the left eye is straight. The cover test is performed by having the child look straight ahead at an object 20 feet away (Fig. 41-14). An eye chart is usually used to test children older than 3 years. For younger children, it is helpful to use a colorful, moving object or toy. As the child looks at the target, cover the child’s right eye and look for movement of the uncovered eye. If the left eye moves to pick up fixation, it was deviated before placing the cover over the right eye. Repeat the procedure for the left eye, and watch for any movement in the uncovered right eye. If the eye moves inward to pick up fixation, the eye is exotropic. If the eye moves outward to pick up fixation, the eye is esotropic. The third test involves simultaneous examination of the pupillary red reflexes. This is a useful test to assess ocular 941

41

Ophthalmology

A

B

C Figure 41-13 Strabismus of right esotropia (A), right exotropia (B), and right hypertropia (C). (From American Academy of Ophthalmology. The Child’s Eye: Strabismus and Amblyopia. American Academy of Ophthalmology, Professional Information Committee, San Francisco, 1982 [AAO. The Child’s Eye.].)

alignment and rule out abnormal ocular media, such as cataracts. The test should be performed in a darkened room with the examiner approximately 18 to 24 inches from the patient. Both red reflexes should be simultaneously assessed and compared using the direct ophthalmoscope. If an abnormality exists in the ocular media, the red reflex will be asymmetric or a white reflex may be present. An abnormal reflex may also signify a high refractive error or a small strabismus. The red reflexes should be equal and symmetric. Ophthalmoscopy also permits direct visualization of the fundus and optic disc. The fourth test checks the extraocular movements in the cardinal positions of gaze (Fig. 41-15). The results of these tests provide a good basis for determining whether there is any misalignment present. This is an important screening for all family physicians to learn, because early intervention can help improve the overall visual and binocular status of the patient. Table 41-5 lists several forms of strabismus. For congenital esotropia, surgery is the primary treatment for this condition and is performed between 6 and 12 months of age (Fig. 41-16). Esotropia may also be related to refractive error and managed with spectacle correction (Figs. 41-17 and 41-18). Large deviations of exotropia and hypertropia are also managed surgically (Figs. 41-19 to 41-23). (See online text for further discussion.)

Pseudostrabismus A common misconception is that children with cross-eye (esotropia) outgrow the condition, but this is generally not the case. This belief stems from confusion between true strabismus and what is known as pseudostrabismus, or false strabismus. 942

Figure 41-14 Cover-uncover test. Evaluate the unoccluded eye for strabismus. (From AAO. The Child’s Eye.)

A child with pseudostrabismus has broad folds of skin that partially cover the top of each eye and a flat nasal bridge that creates the illusion of crossed eyes. As the child ages and the skin fold becomes less apparent, the condition becomes less noticeable. When a child’s eyes are truly crossed, it is always a serious condition and requires the care of an ophthalmologist.

Other Causes of Strabismus Acute strabismus may be brought on by a viral upper respiratory tract infection, which can cause acute cranial nerve VI palsy. With the advent of antibiotics, middle ear infections with associated petrositis and cranial nerve VI palsies are relatively uncommon. Sudden-onset strabismus may also indicate underlying neurologic disease. Another cause is spasm of the near reflex. A hallmark of spasm of convergence is a constricted pupil. Paralytic or mechanical causes of strabismus occur with trauma and Duane’s syndrome. In addition, neurologic trauma accounts for paralysis to cranial nerves III, IV, and VI (Fig. 41-24). The proper corrective treatment for strabismus includes nonsurgical treatment, such as patching and glasses, and surgical treatment, when indicated. Eye muscle surgery is performed when nonsurgical methods cannot correct the misalignment, as well as with worsening misalignment, no effect on the deviation or stereopsis, or progressive loss of fusion. Four aspects of strabismus surgery should also be stressed, as follows: 1. The surgery is safe and effective. 2. The eyeball is never removed from the orbit to perform the surgery. 3. More than one procedure may be required to establish alignment. 4. Both eyes may require surgery to correct the strabismus. The goals when treating strabismus include the ability to provide and maintain equal vision in both eyes, enable the eye to work together rather than independently, and improve depth perception, whenever possible.

KEY TREATMENT Surgical and nonsurgical treatment of strabismus is beneficial to appropriate visual development, reduction of amblyopia, and rehabilitation of sensorimotor function or depth perception (AAO, 2007) (SOR: A).

Ophthalmology

Right superior rectus

RIGHT EYE

Right inferior oblique

Right medial rectus

Right lateral rectus

Right Right inferior superior rectus oblique Figure 41-15 Ocular muscle movement in cardinal fields of gaze.

Left inferior oblique

LEFT EYE

Left superior rectus

Left medial rectus

Left superior oblique

Left lateral rectus

Left inferior rectus

Table 41-5 Classification of Strabismus

Type

Cases (%)

Age of Onset

Congenital or infantile esotropia

20

Birth to 6 mo

Accommodative esotropia

45-50

6 mo to 7 yr (usually 2 yr)

Nonaccommodative (acquired) esotropia

10

Variable, depending on cause

Exotropia

20

Variable (usually during infancy to 4 yr)

Hypertropia

400 mg/dL Patient pregnant or lactating

CT Findings Evidence of intracranial hemorrhage Hypodensity or effacement of the sulci in one third of the region of the middle cerebral artery t-PA, Tissue plasminogen activator (alteplase [Activase]); aPTT, activated partial thromboplastin time; CT, computed tomography; INR, international normalized ratio; GI, gastrointestinal; GU, genitourinary.

is potentially beneficial, there is an approximately 1 in 15 chance of suffering a serious cerebral hemorrhage, even if t-PA is used in accordance with strict guidelines. They should also understand that although patients with severe ischemic strokes have the most to gain from t-PA, they also have a higher risk of t-PA–associated intracerebral hemorrhage. Finally, the CT must not demonstrate intracranial bleeding if t-PA is to be given, and some experts recommend withholding t-PA if the CT demonstrates evidence of early infarction. In some referral centers, intra-arterial thrombolysis is also a treatment option. Such intervention extends the treatment window to 6 hours, principally because of the lower dose of t-PA administered and the ability to deliver the agent directly into the clot. Additionally, mechanical removal of intra-arterial thrombus is also a treatment option, using a 967

42

Neurology

c orkscrew-like mechanism (Merci device) or a suction mechanism (Penumbra device) to extract the clot and thereby reestablish blood flow to the ischemic penumbra.

Pharmacologic Therapy Published studies to date overwhelmingly support the ability of aspirin to reduce stroke incidence and death in patients who present with TIA or CVA. Aspirin and other agents that affect platelet function are frequently used for long-term secondary stroke prevention. It therefore seems reasonable, after hemorrhage has been excluded by CT, to begin aspirin therapy in the setting of acute stroke, provided the patient does not have a contraindication to aspirin therapy. Aspirin doses between 50 and 1300 mg/day have been shown to be effective for stroke prevention. In the absence of convincing evidence favoring a specific dosage, most clinicians prescribe 81 or 325 mg/day. The FDA recommends that aspirin doses of 50 to 325 mg/day be used for stroke prevention. Clopidogrel (Plavix) inhibits platelet function by irreversibly binding to adenosine diphosphate receptors. Compared with aspirin, clopidogrel significantly decreases the constellation of CVA, myocardial infarction (MI), and vascular death and has a toxicity comparable with that of aspirin. Thrombotic thrombocytopenic purpura (TTP) has been reported after the initiation of clopidogrel, often within the first 2 weeks of therapy (Bennett et al., 2000). Dipyridamole (Persantine) was widely used in combination with aspirin in the early 1980s for the prevention of stroke until critical analysis cast doubt on its efficacy. A European study found high-dose sustained-release dipyridamole plus aspirin to be superior to aspirin alone for the prevention of stroke (Diener et al., 1996). The side effects of this therapy included headache and required discontinuation in approximately 6% of patients. Selection of the appropriate antiplatelet agent for stroke prevention can become complicated, especially for patients with comorbid cardiovascular disease. Both extendedrelease dipyridamole plus aspirin (Aggrenox) and clopidogrel (Plavix) are reasonable first line antiplatelet agents for secondary stroke prevention, shown to be more effective than aspirin alone. Randomized controlled trials (RCTs) have shown no additional benefit of the combination of clopidogrel and aspirin, which only increase the risk of hemorrhage. The use of heparin therapy for the prevention of recurrent TIA or stroke progression is limited. Progression of CVA is common, occurring in 15% to 20% of carotid-distribution strokes and 35% to 40% of vertebrobasilar CVAs. Even in patients with angiographically minimal or absent cerebral artery occlusion, clinical worsening of neurologic findings frequently occurs. Furthermore, heparin has not been shown in adequate clinical trials to improve clinical outcome among patients with stroke. The International Stroke Trial (IST, 1997) reported that patients receiving subcutaneous heparin had fewer recurrent ischemic strokes, but this improvement was offset by an increase in hemorrhagic strokes. There was no net benefit. Trials with heparinoids have also failed to demonstrate a clear benefit and have shown an increased risk of non–central nervous system (non-CNS) bleeding. Studies have also failed to demonstrate a clear benefit for low- molecular-weight (LMW) heparin. 968

Box 42-2 Cardiac Conditions Substantially Associated with Embolism Atrial fibrillation Mitral stenosis Mechanical cardiac valves Recent myocardial infarction Left ventricular thrombus, especially if mobile and protruding Atrial myxoma Infective endocarditis Dilated cardiomyopathy Marantic (nonbacterial thrombotic) endocarditis

Currently, warfarin (Coumadin) cannot be recommended as initial therapy for most patients with stroke of primarily cerebrovascular origin. In two large-scale RCTs of warfarin compared with aspirin in the prevention of recurrent stroke (SPIRIT, WARSS), warfarin was not superior to aspirin for patients without cardioembolic disease or operable carotid stenosis (Sacco et al., 2006). Furthermore, the hemorrhagic risk with warfarin was higher than with aspirin. In contrast to ischemic stroke, there is good evidence that warfarin is beneficial for patients with several major cardiac disorders predisposing them to embolic stroke. Box 42-2 summarizes cardiac conditions that are substantially associated with cardioembolic stroke and often warrant prophylactic therapy with warfarin. Other cardiac conditions, such as mitral valve prolapse with or without myxomatous changes, severe mitral annular calcification, and calcific aortic stenosis, have a low or uncertain risk of embolism, and warfarin therapy is generally reserved for secondary prevention.

Management of Acute Stroke Initial Management in Emergency Department Patients suspected of having suffered an acute stroke should be stabilized in accordance with usual emergency management, which focuses initially on basic cardiopulmonary resuscitation (CPR) and support. All patients should have a thorough but timely physical examination, looking especially for head and neck trauma and cardiovascular abnormalities, followed by neurologic evaluation, including assessment of mental status, cranial nerve function, cerebellar function, and motor and sensory function, using the NIH Stroke Scale. Initial laboratory studies should generally include determination of a complete blood count (CBC) with differential and platelet count, prothrombin time and partial thromboplastin time (PT/PTT), electrolyte, blood urea nitrogen (BUN), creatinine, and glucose levels, oxygen saturation by pulse oximetry, and a metabolic panel. Depending on the clinical history, some patients should have studies for possible altered coagulation or connective tissue diseases. A CT scan of the head should be obtained expeditiously to evaluate for hemorrhage. Most patients should have additional studies, including electrocardiography (ECG), chest radiography, echocardiography, and carotid duplex ultrasonography. Consultation with neurology, speech therapy, physical therapy, occupational therapy, and social services should be considered (Box 42-3).

Neurology

Box 42-3 Initial Treatment Considerations for Stroke Patients Provide Initial Care. Stabilize the patient, secure the airway, and provide adequate oxygenation. Assess level of consciousness, language, visual fields, eye movements, and pupillary movements. Obtain history and perform physical examination. Perform CT of head without contrast. Obtain CBC with platelets and differential, electrolytes, creatinine, BUN, glucose, PT/PTT, and oxygen saturation.

Consider Toxicology Screen. Consider special coagulation studies such as antiphospholipid antibodies, factor V Leiden assay, protein C and protein S, antithrombin III, ANA, fibrinogen, RPR, homocysteine, serum protein electrophoresis, prothrombin gene 20210.

Consider Acute Intervention with T-PA. Consider the Following with Admission Orders: Transesophageal echocardiography Carotid duplex ultrasonography Telemetry Supplemental oxygen and appropriate oxygen saturation monitoring Antiplatelet therapy Fluid restriction if infarct is large, to reduce cerebral edema Close monitoring of intake and output Regular determinations of blood glucose levels to avoid hyperglycemia NPO until there is certainty about the gag reflex pending swallowing evaluation Elevate head of bed 20 to 30 degrees to reduce cerebral edema. Bed rest for first 24 hours with fall precautions, then advance as appropriate. Vital signs and neurologic checks every 2 hours × 4, then every 4 hours for 24 hr Prophylaxis for DVT while immobile Speech therapy consultation to evaluate swallowing Neurology, physical therapy, occupational therapy, nutrition, and social services consultations ANA, Antinuclear antibodies; BUN, blood urea nitrogen; CBC, complete blood count; CT, computed tomography; DVT, deep vein thrombosis; NPO, nothing by mouth; PT/PTT, prothrombin time/partial thromboplastin time; RPR, rapid plasma reagin; t-PA, tissue plasminogen activator.

Elevated Blood Pressure During the first day after an ischemic stroke, elevated blood pressure (BP) should not be treated unless systolic is consistently higher than 220 mm Hg or diastolic is consistently higher than 120 mm Hg. There are exceptions to this recommendation. Patients who have received t-PA should have BP maintained below 185/110 mm Hg, and patients with MI, heart failure, aortic dissection, or renal failure should have more aggressive BP control. Areas of cerebral ischemia lose their normal autoregulatory capacity, and tissue perfusion becomes directly linked to mean arterial pressure. When cerebral ischemia occurs, BP elevations are often transient and spontaneous declines common. Overzealous BP treatment can therefore convert an area of ischemia that retains the potential for recovery into an area of frank infarction with no potential for recovery.

Box 42-4 Antihypertensive Agents for Patients with Acute Stroke Labetalol (Normodyne) 10 mg intravenously (IV) over 1 to 2 minutes; may repeat or double dosage every 10 to 20 minutes until blood pressure controlled or maximum dose of 300 mg has been reached. 100 mg orally twice daily Nicardipine (Cardene) 5 mg/hr IV, titrated upward as necessary, typically to a maximum of 15 mg/hr Sodium nitroprusside (Nipride) 0.3 μg/kg/min IV, titrated upward as necessary, typically to a maximum of 10 μg/kg/min

When antihypertensive agents are used shortly after CVA, one with rapid action and predictable response, such as nicardipine (Cardene), labetalol (Normodyne), or sodium nitroprusside, should be chosen (Box 42-4). Nicardipine is currently considered first-line treatment in this setting. Labetalol is preferable to sodium nitroprusside because of nitroprusside’s ability to cause cerebral vasodilation, which can worsen cerebral edema in some patients. Sublingual calcium channel antagonists should be avoided because of their ability to cause precipitous BP declines, which could significantly reduce cerebral blood flow and result in further ischemic damage.

Cerebral Edema Cerebral edema usually peaks within 2 to 4 days after a stroke. It is seldom a problem during the first 24 hours, except in cases of large cerebellar CVAs. Steroids are not used to treat cerebral edema related to thromboembolic strokes. Steroids are generally ineffective and may exacerbate hyperglycemia and raise BP. Cerebral edema related to thromboembolic stroke is first treated by raising the head of the bed 20 to 30 degrees. Hyperventilation can work rapidly to reduce intracranial pressure (ICP) but has only a transient effect. Mannitol can be given to lower ICP at 0.25 to 0.5 g/kg intravenously (IV) over 30 minutes, but its use is controversial because of possible pooling in the area of ischemia and potential worsening of edema. Mannitol can rapidly lower ICP and can be repeated every 6 hours. The maximum dose of mannitol is 2 g/kg IV. Hypertonic saline has also been used to reduce cerebral edema in this context. Hemicraniectomy with durotomy is performed for malignant MCA-distribution infarct in select cases and has been shown to improve survival and functional outcome.

Other Management Issues Hypoxia should be avoided. Any circumstance that is likely to impair oxygen delivery to the ischemic penumbra needs to be avoided. Patients with acute stroke should therefore have their oxygen saturation monitored, and supplemental oxygen provided if desaturation occurs. The use of subcutaneous heparin for the prevention of deep venous thrombosis (DVT) in nonhemorrhagic stroke patients has been well accepted. Heparin should be dosed based on weight. LMW heparin is a reasonable alternative in this setting. Intermittent pneumatic compression stockings are the best prophylactic alternative for patients unable to receive 969

42

Neurology

anticoagulants. Patients able to ambulate 50 feet daily are at low risk for venous thromboembolism. Fever is seen quite often after an acute stroke. Regardless of cause, fever should be reduced, because ischemic cerebral insults accompanied by even mild elevations in body temperature have been associated with less favorable outcomes in both experimental models and clinical studies. Hyperglycemia can be harmful for the ischemic penumbra because it permits anaerobic metabolism, which results in local generation of lactic acidosis. Serum glucose levels should generally be maintained below 150 mg/dL. Nevertheless, it should be recognized that controlling blood glucose has not been shown to improve stroke outcome in humans. Patients who suffer a seizure after a stroke have a higher mortality. Some believe that such patients should receive anticonvulsant therapy indefinitely, whereas others note that a trial off medication after several years without seizure activity seems reasonable.

Delirium Key Points • A confused older adult patient should generally be assumed to have delirium until proved otherwise. • Delirium is a transient, global disorder of cognition and consciousness; changes in consciousness typically develop quickly and fluctuate during the day. • Underlying dementia is a significant risk factor for delirium. • The history, physical examination, and test results usually suggest a cause for delirium. • Delirium is best managed by correction of the causative disturbances.

Delirium is a common problem encountered in patients seen by family physicians, especially in the hospital or skilled nursing facility. Delirium is characterized by a change in cognition and attention that develops rapidly, usually over hours to days, and fluctuates throughout the day. It may pre sent as hyperactive delirium, with agitation, disorientation, and delusions; hypoactive delirium, demonstrated by the lethargic patient who is difficult to arouse and engage in conversation; or a mixed-type delirium with features of both. Hypoactive delirium is the most common encountered form of delirium, which may explain why it goes unrecognized in up to 70% of patients experiencing delirium (Gillis et al., 2006). Because of this, any confused older adult patient should generally be assumed to have delirium until proved otherwise. Delirium is a serious condition that has long-term ramifications, including increased hospital length of stay, increased mortality, failure to return to baseline cognitive and functional status, and increased need for prolonged, skilled nursing facility care. Box 42-5 summarizes risk factors for the development of delirium. Two thirds of delirium cases occur in patients with underlying dementia, placing these patients at significant risk when being treated for other health problems (Cole, 2004). The mainstay of treatment for delirium is to identify and correct the underlying cause. This cause can usually be determined through a thorough history, physical examination, and evaluation of selected laboratory tests. Box 42-6 970

Box 42-5 Risk Factors for Development of Delirium Age >65 years Chronic kidney disease Dehydration Dependence with activities of daily living Hearing impairment Infection Malnutrition Multiple comorbid conditions Polypharmacy Underlying dementia Vision impairment

Box 42-6 Common Causes of delirium Dehydration Electrolyte abnormalities Infection Myocardial infarction Heart failure Neurologic disorder (stroke, seizure) Hypoxia Medications (anticholinergics, antihistamines, antidepressants, benzodiazepines, narcotics) Intoxication Environmental changes (change in location or caregiver, overstimulation) Pain Sleep deprivation Surgery Urinary catheter Urinary retention Fecal impaction

s ummarizes some of the common causes that should be considered. Special attention should focus on recently started medications. Although almost any medication can precipitate delirium, analgesics, antiarrhythmics, antidepressants, Parkinson’s medications, and anticholinergic medications such as antihistamines, benzodiazepines, β-blockers, calcium channel blockers, steroids, diuretics, clonidine, and digoxin are common culprits. A targeted laboratory evaluation should be undertaken, including a CBC, determination of electrolytes, BUN, creatinine, glucose, calcium, magnesium, phosphate, and liver function tests (LFTs). Oxygenation should be assessed by oximetry or arterial blood gases (ABGs). ECG should be considered, especially for patients with angina, dyspnea, or a cardiac history. A chest x-ray film and urinalysis to evaluate for occult infection, especially in older-adult patients, should also be considered. If this evaluation does not elicit a likely cause for a patient’s delirium, further testing may be necessary. Additional laboratory studies to consider include thyroid function tests, human immunodeficiency virus (HIV) testing, rapid plasma reagin (RPR) test, drug levels, toxicology screening, serum ammonia level, and serum vitamin B12 level. Lumbar puncture is usually reserved for patients with fever and signs

Neurology

suggesting meningitis. Neuroimaging may be indicated for patients with new neurologic signs or a history of head trauma. EEG may be helpful in the evaluation of patients with a suspected seizure disorder or to differentiate delirium from a functional psychiatric disorder. Delirium can be treated with both nonpharmacologic and pharmacologic measures. Environmental modifications should be instituted early, before pharmacologic intervention or mechanical restraint is considered. A supportive and familiar environment should be created for the patient. Family members should be encouraged to remain nearby as much as possible. The staff should visit the patient frequently or move the patient to be near them. The room should be well illuminated, with a large, easily read clock and calendar. The family should bring familiar items from home to be placed in the patient’s room. Whenever possible, normal sleep hygiene patterns should be maintained with minimal interruptions during the night hours. Pharmacologic management of delirium should be considered when the previous treatments have failed to control agitation and should involve the use of antipsychotic medications. Among the antipsychotic agents, haloperidol (Haldol) at 1 to 2 mg orally every 4 hours as needed, or 0.25 to 0.5 mg orally every 4 hours for elderly patients, is recommended (American Psychiatric Association, 1999). Other antipsychotic medications, such as risperidone (Risperdal), 0.5 to 1 mg orally daily, and olanzapine (Zyprexa), 2.5 to 5 mg orally daily, may also be used; as yet, no RCTs have established the safety and effectiveness of one antipsychotic medication over another for the management of delirium symptoms (Seitz et al., 2007). Risperidone and olanzapine do not work as quickly as haloperidol, often require slow titration, and can be associated with significant orthostasis. More recent studies have also demonstrated a potentially elevated risk of mortality in older adults with dementia who were treated with atypical antipsychotics (Schneider et al., 2005). Therefore, these risks must be considered when initiating pharmacologic treatment for delirium. Further recommendations for initiating antipsychotics for the treatment of delirium include using the lowest possible doses, frequent reassessments to limit the duration of antipsychotic use, and a baseline ECG to rule out susceptibility to an arrhythmia from a prolonged QT interval (Seitz et al., 2007). Lorazepam (Ativan), a benzodiazepine, has also been used for the treatment of agitation associated with delirium, although a Cochrane review concluded that benzodiazepines cannot be recommended for the treatment of non-alcohol-related delirium (Lonergan et al., 2009). Physical restraints should be a last resort, reserved for the protection of patients who do not adequately respond to environmental and pharmacologic interventions.

Dementia Key Points • D ementia is a gradual, progressive impairment of memory and other cognitive functions that is severe enough to impact work, social activities, and relationships. • Dementia can be divided into four categories: Alzheimer’s disease (60% of cases), dementia with Lewy bodies (15%), vascular dementia (15%), and all other causes (10%).

• C omprehensive, longitudinal, well-coordinated care delivered by the family physician for both the patient and the caregiver is the cornerstone of effective management of patients with dementia. • The cholinesterase inhibitors are effective in slowing the progression of cognitive and functional decline and may be used in conjunction with memantine (NMDA receptor antagonist) to treat moderate to severe dementia.

Dementia is characterized by the development of an acquired impairment in memory associated with impairment in one or more cognitive domains, including executive function, language (expressive or receptive), praxis (learned motor sequences), or gnosis (ability to recognize objects, faces, or other sensory information). The impairments are severe enough to interfere with work, social activities or relationships (American Psychiatric Association, 1994). The course is usually one of gradual, progressive decline and causes impairment in the ability to perform activities of daily living (ADLs). The incidence of dementia increases with age. By 75 years, 10% to 15% of people have dementia, increasing to 35% to 50% for those over 85.

Classification and Pathophysiology Dementia is usually divided into four main categories. Dementia of Alzheimer’s type accounts for approximately 60% of cases; dementia with Lewy bodies, 15%; and vascular dementia, 15%. The remaining category includes multiple other forms, including mixed dementias that exhibit components of both Alzheimer’s and vascular dementia and dementias resulting from CNS trauma, Parkinson’s disease, Pick’s disease, Creutzfeldt-Jakob disease, and Huntington’s disease. Alzheimer’s disease patients have brains that demonstrate atrophy with ventricular and sulcal enlargement. They reveal evidence of neuronal loss as well as the presence of amyloid plaques and neurofibrillary tangles. Amyloid plaques are composed of misfolded β-amyloid that initiates a pathogenic cascade resulting in neurotoxicity and nerve cell death. Dementia with Lewy bodies is similar to Alzheimer’s disease, but visual hallucinations and motor symptoms similar to parkinsonism develop early in the course of the disease. Histologically, Lewy bodies are present, cytoplasmic inclusions found in the temporal, parietal, and paralimbic regions of the brain. Vascular dementia is usually subdivided into multi-infarct dementia and subcortical vascular dementia. Multi-infarct dementia should be suspected when focal, asymmetric neurologic abnormalities accompany dementia. Neuroimaging may show multiple strokes. Subcortical vascular dementia should be suspected if the patient manifests significant problems with gait early in the course of the dementia. The CT or magnetic resonance imaging (MRI) scan is usually normal in these patients, except for increased signal in the deep white matter, a nonspecific sign.

Evaluation The diagnosis of dementia is still made clinically, so evaluation of a patient with suspected dementia begins with a complete history and physical examination. The history should include questions regarding the time frame surrounding 971

42

Neurology

symptom progression. The relation to any recent vascular events such as stroke should be noted. Risk factors for vascular disease (hypertension, diabetes, hyperlipidemia, atrial fibrillation, smoking history) should be reviewed. Changes in the ability to perform ADLs should also be addressed. The patient’s ability to perform dressing, eating, ambulating, toileting, and bathing tasks should be recorded as independent, requiring assistance, or dependent. The physical examination should include a thorough neurologic examination for signs of underlying vascular disease and stoke. Cognitive testing should be done, ideally with the Mini–Mental State Examination, which allows for quantification of cognitive impairment over time (Table 42-4). A score less than 24 is considered abnormal, but because of educational bias, highly educated patients may have inflated scores and those with limited education artificially low scores (Tombaugh, 1992). When considering which tests to perform as part of the evaluation of a patient with dementia, physicians have traditionally been taught to search for reversible causes of dementia. It is now recognized that reversible dementia rarely occurs (Sloane, 1998). Current recommendations for laboratory testing generally recommend that all patients be evaluated with a CBC, thyroid-stimulating hormone (TSH), serum calcium, electrolytes, and fasting glucose, as well as a serum B12 level. Selective testing based on the presenting medical history, physical examination, and cognitive testing may include a red blood cell (RBC) folate level, RPR for syphilis screening, and HIV antibodies. Testing for

homocysteine levels and genetic testing for apolipoprotein E gene is not recommended (Feldman, 2008). Although neuroimaging is not recommended for all patients in the workup of dementia, selective use of CT or MRI is recommended for patients with suspected tumor, subdural hematoma, or normal-pressure hydrocephalus (NPH) (Feldman et al., 2008).

Management

Max Score*

Task

5

Orientation: Year, season, date, day, and month.

Comprehensive, longitudinal, well-coordinated care delivered by the family physician for both the patient and the caregiver is the cornerstone of effective management of patients with dementia. Patients should be seen regularly in the office, and the physician should be readily available by telephone. The family should maintain frequent contact with the patient and physician. The family physician should update vaccinations, monitor visual acuity and hearing, and address other appropriate health issues. Families should be counseled regarding behavioral and environmental modifications that may be helpful, including reducing hazards in the home for falls and injuries. A discussion regarding the timing of cessation of driving should be undertaken early in the course of treatment. Decisions regarding advanced directives and planning for the later stages of the disease should begin early in the process as well. The patient should legally designate a durable power of attorney for health care. The discussion of the placement of feeding tubes should begin before difficulties with feeding develop. Families should be aware that feeding tubes do not prolong life, are associated with discomfort and medical complications, and are generally not recommended for patients in the final stages of a dementing illness (Li, 2002). The role of palliative care and hospice care should also be discussed early in the course of the illness, when the patient has the opportunity to participate in the decision-making process.

5

Orientation: State, county, town, building, and floor (as applicable)

Pharmacotherapy

3

Registration: Name three objects. Record the number of trials required to learn.

5

Attention and calculation: Serial 7 subtraction: Subtract from 100 by 7 (stop after 5 answers) or Spell the word “world” backward (score number of correct letters in correct location).

3

Recall: Recall the three objects registered above.

2

Language: Name two objects (pencil and watch).

1

Repeat “No ifs, ands, or buts.”

3

Follow a three-step command.

1

Read and obey: “Close your eyes” written in print large enough for patient to see clearly.

1

Write a sentence.

1

Copy a picture of intersecting pentagons.

Table 42-4 Mini–Mental Status Examination

Modified from Folstein MF, Folstein SE, McHugh PR. Mini–Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189. *Total possible score: 30.

972

The cholinesterase inhibitors donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon) have received FDA approval for the treatment of patients with Alzheimer’s disease. Tacrine (Cognex), which is associated with elevated liver transaminase levels in about 30% of patients, is rarely used. The cholinesterase inhibitors act by blocking acetylcholinesterase breakdown of acetylcholine, believed to increase acetylcholine in affected areas of the brain. All these agents show comparable response rates, and choice is therefore individualized according to patient and caregiver needs as well as the drug’s side effect profile. Pharmacologic effectiveness is measured by a slowing of the decline in cognitive and global functioning over 6 to 12 months. The cholinesterase inhibitors are generally well tolerated, although side effects include nausea, vomiting, diarrhea, dyspepsia, anorexia, weight loss, bradycardia, and agitation. When these medicines are discontinued, the patient may experience a rapid decline in global functioning. Another medication, memantine (Namenda), an N-methyld-aspartate (NMDA) receptor antagonist, has been FDA approved for the treatment of moderate to severe dementia as monotherapy or in combination with a cholinesterase inhibitor (Reisberg, 2003). Memantine appears to have fewer

Neurology

side effects than the cholinesterase inhibitors, although dizziness, insomnia, and hallucination may be seen. Alternative agents such as Ginkgo biloba, nicotine, vitamin C, and vitamin E could be beneficial in the treatment of Alzheimer’s disease. At present, however, no other prescribed medication, supplement, or herbal preparation can be recommended for the cognitive or functional manifestations of dementia (Hogan et al., 2008).

multiple recordings can also increase the diagnostic yield. In some cases, accurate diagnosis can be accomplished only with continuous video and EEG monitoring. A small number of patients with seizure disorders have normal interictal EEG recordings, despite efforts made to record epileptiform abnormalities.

Seizures

Febrile seizures are seizures without a definite cause that are associated with fever. Febrile seizures, by definition, do not include seizures occurring in patients with an intracranial infection, such as meningitis or encephalitis, toxic encephalopathy, or any other neurologic illness. The definition also excludes seizures associated with fever that occur in patients who have a history of a previous nonfebrile seizure. Febrile seizures usually occur in children between the ages of 3 months and 5 years and represent the most common convulsive disorder of young children, affecting 2% to 5% of U.S. children. The most common age of onset is in the second year of life, and boys are affected slightly more often than girls (Freeman and Vining, 1995; Hirtz, 1997). Risk factors for a first febrile seizure include a family history of febrile seizures, developmental delays, very high fever, and child care attendance. Approximately one third of children who experience a first febrile seizure will experience at least one more. The younger the child when the first febrile seizure occurs, the more likely the child is to have another febrile seizure. Most recurrences occur within 1 year. A family history of febrile seizures also increases the likelihood of recurrence. Fortunately, less than 5% of children who experience a febrile seizure develop epilepsy. Febrile seizures can be of any type, but are most often tonic-clonic. Febrile seizures are usually shorter than 6 minutes, and fewer than 8% last longer than 15 minutes. Most children therefore do not come to the attention of the family physician until after the seizure is over. Although it is commonly believed that the rate of fever increase is an important factor in the development of febrile seizures, no data support this as being more important than fever severity.

Key Points • F ebrile seizures usually occur between age 3 months and 5 years and represent the most common convulsive disorder of young children (2%-5%). • Risk factors for a first febrile seizure include family history, developmental delays, high fever, and child care attendance.

One in 11 Americans who lives to the age of 80 years experiences at least one seizure. About 1% of the U.S. population have epilepsy or recurrent unprovoked seizures. Treatment of patients with epilepsy reduces the risk of recurrent seizures while optimizing quality of life. This requires minimizing the adverse effects of antiepileptic medications and maximizing the patient’s ability to engage in normal activities and responsibilities (Scheuer and Pedley, 1990). Seizures are a manifestation of disturbed neurologic function and therefore often associated with acute neurologic disorders such as meningitis. In some patients the seizures are self-limited and resolve when an acute neurologic disturbance resolves. In others the seizures persist and result in a diagnosis of epilepsy. Some patients who appear medically and neurologically normal after appropriate evaluation may experience a single seizure and the cause never determined. Such patients do not have epilepsy. Seizures are typically classified as partial or generalized. Partial, or focal, seizures arise in a portion of one cerebral hemisphere and are accompanied by focal EEG abnormalities, whereas generalized seizures appear to involve simultaneously all or large parts of both cerebral hemispheres from their onset. Partial seizures are subclassified according to whether consciousness is preserved (simple partial seizures) or impaired (complex partial seizures). Generalized seizures are subclassified by their associated patterns of convulsive movements (Box 42-7). It is not always possible to classify accurately a seizure based exclusively on clinical observations. A seizure with generalized convulsive activity may have a focal onset with rapid generalization. Such a seizure would best be classified as a partial seizure with secondary generalization, rather than as a generalized tonic-clonic seizure. Accurate classification of such a seizure could not be accomplished, however, without EEG. Also, not every paroxysmal event that appears to be a seizure is a seizure. Movement disorders, psychological disorders, and sleep disorders can produce activity that is similar to seizure activity. Thus, accurate seizure diagnosis often requires both clinical observation and corroborative EEG. Because EEG is usually done in the absence of seizures, certain steps should be taken to increase its diagnostic yield. Both sleep and sleep deprivation increase the likelihood of recording epileptiform abnormalities by EEG. Obtaining

Febrile Seizures

Box 42-7 Seizure Classification Partial Seizures Simple (consciousness is preserved) Complex (consciousness is impaired) Secondarily generalized Simple partial seizures evolving to generalized tonic-clonic Complex partial seizures evolving to generalized tonic-clonic Simple partial seizures evolving to complex partial, then to generalized tonic-clonic

Generalized Seizures Tonic-clonic Absence Atypical absence Myoclonic Tonic Atonic

973

42

Neurology

The evaluation of a child who has had a febrile seizure should begin with a careful history and physical examination. The history should include symptoms of infection, medication use, toxic ingestions, developmental and health problems, prenatal/birth and family history, and detailed description of the seizure by witnesses. The physical examination should pay particular attention to signs of severe illness, including petechiae, meningismus, tense or bulging fontanelle, Kernig’s and Brudzinski’s signs, and signs of neurologic abnormality, including decreased alertness or cognition and deficits of motor strength or tone. Even in children with a previous history of febrile seizures, a seizure associated with fever may be a sign of an intracranial infection. If intracranial infection is suspected, a lumbar puncture (LP) should be performed. Otherwise, LP is not necessary. Children older than 18 months who have meningitis or encephalitis usually demonstrate typical clinical signs and symptoms. Many of these children lack histories, symptoms, or signs suggesting meningitis and thus do not require LP. However, children younger than 12 to 18 months may lack the typical clinical signs and symptoms of intracranial infection and are more likely to require LP. If a child is already taking antibiotics and experiences a seizure associated with fever, partially treated meningitis should be considered. The presence of a source of infection, such as otitis media, does not exclude the possibility of meningitis. Other features in the history that should also raise suspicion of meningitis in children with seizures and fever include evaluation for illness by a physician within the past 48 hours, a seizure that occurs in the office or emergency department (ED), or a focal seizure. Most children with febrile seizures do not require routine laboratory testing. The only laboratory studies needed are those that will assist in evaluating the source of the child’s fever. Radiography of the skull, neuroimaging studies such as CT and MRI, and EEG are not usually indicated. Children who are diagnosed with a febrile seizure should be observed in the ED or physician’s office for several hours. These children may then be sent home, provided (1) they demonstrate satisfactory clinical improvement and are alert, (2) their fever has been appropriately evaluated and treated, and (3) close outpatient follow-up is possible. If there is any question about intracranial infection, if a child does not demonstrate expected clinical improvement during observation, or if follow-up cannot be ensured, hospital admission is recommended. One of the most important components of outpatient management of children with febrile seizures is education of the parents. Seizures are frightening events for most parents. They should be reassured that febrile seizures do not result in brain damage and that the risk of epilepsy is very low. Slightly more than one in six children, however, experience another seizure within 24 hours, and about one in three experiences another febrile seizure at some point. If another seizure occurs, parents should be advised to place the child on his or her side or face down on the abdomen. Contrary to common belief, they should not attempt to place anything between the child’s teeth during a seizure. The parents should carefully observe the child, and if the seizure does not spontaneously resolve after 10 minutes, they should call 9-1-1. Parents may have concerns about routine vaccinations for children with a history of febrile seizures. The diphtheria and tetanus toxoids and pertussis (DTP) and measles, 974

mumps, and rubella (MMR) vaccinations are most likely to produce fever associated with seizure. If a febrile seizure is going to occur after vaccination, it is most likely to occur within 48 hours of the DTP vaccination or within 10 days of the MMR vaccination.

Initial Diagnostic Evaluation of a First Seizure in Adults A careful history and physical examination, along with routine blood work, can detect many medical problems that may be associated with seizures. Such problems include infection, electrolyte and glucose abnormalities, impaired hepatic or renal function, and cardiopulmonary disease. Most patients with new-onset seizures should have a CBC with platelet count and differential, toxicology screen, thyroid function testing, PT/PTT, determination of serum transaminase, electrolyte, calcium, magnesium, phosphorus, BUN, creatinine, glucose, ABGs, or pulse oximetry. If cardiopulmonary disease is suspected, ECG and chest radiograph should be obtained. Meningitis or encephalitis suspected clinically indicates LP, which is otherwise not necessary. Patients usually recover rapidly after a first seizure, and their clinical progress can be gauged after several hours of observation. Hospitalization is not usually necessary after a first seizure unless an underlying illness is suspected or there are concerns about the patient’s clinical progress, inadequate social support or observation, or patient’s ability or motivation to complete outpatient follow-up. Patients with new-onset seizures should be scheduled for appropriate EEG and neuroimaging studies. MRI and CT are important complements to EEG because of their ability to identify structural abnormalities that may be related to the development of seizures. MRI is preferable to CT because of its superior ability to identify cortical architectural abnormalities, visualize the temporal lobes, detect gliomas, and identify cavernous malformations. CT, however, is appropriate in the emergency setting because it is readily available and can detect hemorrhages acutely. If the patient is seen in the office shortly after a first seizure, neuroimaging does not need to be performed immediately unless the history and physical examination suggest focal brain injury or marked cognitive impairment. In contrast to MRI and CT, positron emission tomography (PET) and single-photon emission CT (SPECT) can provide functional views of the brain. These studies can identify areas of relative hypoperfusion or hypometabolism that appear to be structurally normal but might play an important role in the development of partial seizures. Although such studies can be useful, especially for patients with conditions such as localization-related epilepsy, they are not routinely obtained or widely available.

Pharmacologic Therapy Whether antiepileptic drug therapy should be initiated after a first seizure remains a topic of debate. The data regarding the likelihood of recurrent seizures after a first seizure are wanting or questionable, and estimates of the rate of recurrence after a single unprovoked seizure range widely. Certain findings and characteristics do seem to increase the likelihood of recurrence after a first seizure, including EEG abnormalities, previous neurologic injury, partial seizures, and a

Neurology

family history of seizures. Also, it is not known whether antiepileptic pharmacologic therapy following a single seizure alters the subsequent risk of epilepsy. Because of these uncertainties and because antiepileptic pharmacologic therapy is associated with a significant incidence of adverse effects, often exceeding the risk of recurrent seizures, many family physicians elect not to prescribe antiepileptic medications for most patients after a single seizure. Although many agents are available for the treatment of seizures, carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital, and divalproex (Depakote) have been traditional first-line therapies for most patients with epilepsy. Increasing availability of newer agents to treat seizures has often resulted in more favorable side effect profiles. Phenobarbital is the oldest agent but has certain disadvantages. Its adverse effects include irritability, decreased cognition, and hyperactivity or lethargy. The degree of sedation and cognitive effects produced at therapeutic dosages are frequently significant enough that many family physicians do not prescribe phenobarbital as a first-line agent. The recommended dosage for common antiepileptics and adverse effects are summarized in Table 42-5. Most patients with epilepsy can achieve remission with the use of a single medication. Because the addition of another antiepileptic agent is usually associated with an increase in adverse drug effects, patients not controlled with one agent should be given a trial of a different agent rather than combining agents early in the course of treatment. Treatment with more than one agent is usually attempted only after a number of trials of monotherapy have failed. Family physicians should exercise caution when measuring levels of antiepileptic drugs. Therapeutic ranges for most antiepileptics are only guidelines for treatment. Some patients achieve therapeutic remission without significant side effects with drug concentrations ordinarily toxic. Other patients develop intolerable side effects with subtherapeutic serum levels. Serum levels of most antiepileptic drugs should generally be determined when remission of seizures is achieved or the patient develops significant side effects. Drug concentrations can also provide evidence of compliance. More frequent serum testing is necessary for patients taking more than one agent, pregnant women, older adults, patients with hepatic or renal dysfunction, and patients taking medications for other medical problems. Box 42-8 lists drugs used to treat other medical conditions that can lower the seizure threshold. Nevertheless, serum levels should not be the primary basis for decisions regarding antiepileptic drug dosing. Seizure control and the development of adverse effects related to drug therapy are more important than serum levels alone.

Status Epilepticus Status epilepticus is generally defined as more than 30 minutes of unconsciousness and continuous or intermittent, generalized seizure activity. However, because most seizures last 2 minutes or less, any seizure longer than 5 minutes may progress to status epilepticus. Patients with recurrent seizures without recovery to wakefulness should also be considered to be in status epilepticus. Status epilepticus can be alarming to observe, even for experienced clinicians. A systematic approach to patients in status epilepticus can facilitate

ptimal patient care during such an episode. The first step o in the management of patients with status epilepticus is to support vital functions. The airway should be protected. Although the patient should be intubated if necessary, this usually requires neuromuscular blockade, and bag and mask ventilation is often preferable. The patient’s vital signs should be closely monitored, including continuous oximetry and ECG. Supplemental oxygen at a rate of about 4 L/min is recommended. Intravenous access should be secured for the administration of parenteral medications and blood drawn for a CBC, toxicology screen, and determination of electrolyte, glucose, calcium, magnesium, and anticonvulsant drug levels. The patient should receive thiamine, 100 mg IV, followed by 50 mL of D50W. If the patient continues to seize, parenteral agents may be given, including lorazepam, 0.1 mg/kg IV at 2 mg/min, or diazepam, 0.2 mg/kg (max 10 mg) at a maximum rate of 5 mg/min. These agents have a relatively rapid onset and short duration of action. Simultaneous loading with phenytoin is therefore recommended. Phenytoin is loaded at 20 mg/kg IV at a rate of less than 50 mg/min through a line infusing glucose-free saline, to avoid precipitation of phenytoin in the line. Fosphenytoin (Cerebyx) is the prodrug of phenytoin and has a more favorable safety profile compared with phenytoin, can be given at a faster rate (150 mg/min), and converts to phenytoin after first-pass metabolism, but it is more costly than phenytoin. Blood pressure and cardiac rhythm must be closely observed because of the ability of phenytoin to precipitate hypotension and heart block. If these side effects appear, they often resolve when the rate of administration is decreased. If seizures continue despite these measures, phenobarbital may be administered parenterally. As a last resort, barbiturate coma or general anesthesia can be instituted. Propofol (Diprivan) and midazolam (Versed) administered as continuous IV drips are often used in neurocritical care settings to induce coma for status epilepticus.

Central Nervous System Infection and Inflammation Key Points • B acterial meningitis is a neurologic emergency. • Acute bacterial meningitis has a high morbidity and mortality. • Antibiotic therapy should be started as soon as possible after meningitis is considered likely, usually by CSF analysis. • Knowing the most prevalent organisms that cause bacterial meningitis in different age groups is important in guiding therapy. • Gram stain of CSF is recommended for all patients with suspected bacterial meningitis. • Adjunctive dexamethasone therapy for infants, children, and adults who have already received antibiotics is not recommended.

Bacterial Meningitis Acute bacterial meningitis has a high morbidity and mortality rate, even under the best circumstances. For this reason, prompt recognition of the clinical syndrome, performance of appropriate testing to confirm the diagnosis, and initiation of appropriate therapy are essential. 975

42

Neurology

Table 42-5 Common Antiepileptic Agents

Agent

Usual Dosage

Adverse Effects

Carbamazepine (Tegretol)

Start: 3 mg/kg/day (adults), 5 mg/kg/day (children) Maintenance: 5-20 mg/kg/day (adults), 20-40 mg/kg/day (children) Usually divided qid

Drowsiness or agitation, diplopia and blurred vision, disequilibrium, benign leukopenia, hepatic failure, rare SIADH, rare aplastic anemia

Phenytoin (Dilantin)

Start: 4-6 mg/kg/day (adults), 3-10 mg/kg/day (children) Maintenance: same Usually divided tid

Dose related: nausea and vomiting, nystagmus, ataxia Not dose related: gingival hyperplasia, hirsutism, acne, coarsening of features, hepatic failure, osteomalacia

Divalproex (Depakote)

Start: 10-15 mg/kg/day Maintenance: 15-30 mg/kg/day Usually divided bid-qid

Transient GI side effects Toxic effects: tremor, thrombocytopenia Side effects: weight increase, alopecia, hepatotoxicity (controversial whether LFTs detect in time to avoid), pancreatitis

Phenobarbital

Starting and maintenance: 1-3 mg/kg/day (adults) and -5 mg/kg/day (children) Usually given in single or divided doses

Lethargy, sedation, decreased cognition, decreased attention, hyperactivity, depression

Levetiracetam (Keppra)

Start: 1000 mg/kg/day (adults), 20 mg/kg/day (children) Maintenance: max 3000 mg/day (adults), 60 mg/kg/day (children) Usually divided bid

Depression, hostility, aggressive behavior, psychosis, somnolence, headache, URI symptoms, infection, fatigue, irritability

Oxcarbazepine (Trileptal)

Start: 600 mg/day (adults), 16 mg/kg/day (children) Maintenance: max 2400 mg/day (adults), 60 mg/kg/day (children) Usually divided bid

Hyponatremia, hypersensitivity reaction, leukopenia, thrombocytopenia, angioedema, Stevens-Johnson syndrome, dizziness, somnolence, diplopia, headache, nausea, ataxia

Lamotrigine (Lamictal)

Start: dosing varies with concomitant anti-epileptics Maintenance: max 400 mg/day Usually divided bid

Rash, Stevens-Johnson syndrome, angioedema, neutropenia, pancreatitis, dizziness, headache, ataxia, nausea, somnolence

Tiagabine (Gabitril)

Start: 4 mg/day (adults/children >12 yr) Maintenance: max 56 mg/day Usually divided bid-qid

CNS depression, seizures, weakness, rash, dizziness, asthenia, somnolence, nausea, diarrhea, tremor, confusion, impaired concentration

Gabapentin (Neurontin)

Start: 300 mg/day (adults), 10 mg/kg/day (children) Maintenance: up to 3600 mg/day (adults), 50 mg/kg/day (children) Usually divided tid

Leukopenia, depression, dizziness, somnolence, ataxia, fatigue, peripheral edema, weight gain, tremor, diarrhea

Pregabalin (Lyrica)

Start: 150 mg/day (adults) Maintenance: up to 300 mg/day Usually divided bid-tid

Thrombocytopenia, hypersensitivity reaction, angioedema, dizziness, somnolence, ataxia, peripheral edema, weight gain

Lacosamide (Vimpat)

Start: 100 mg/day (adults) Maintenance: up to 400 mg/day Usually divided bid

Syncope, atrial fibrillation (rare), dizziness, headache, diplopia, vomiting, fatigue, ataxia

Rufinamide (Banzel)

Start: (Lennox-Gastaut) 10 mg/kg/day (children) Maintenance: 45 mg/kg/day Usually divided bid

Suicidality, seizures, QT shortening, hypersensitivity reaction, leucopenia, somnolence, vomiting, headache, dizziness, nausea

Vigabatrin (Sabril)

Start: (infantile spasms) 50 mg/kg/day (children) Maintenance: up to 150 mg/kg/day Usually divided bid

(Restricted in U.S.) permanent vision loss, anemia, neuropathy, headache, dizziness, fatigue, somnolence, weight gain

LFTs, Liver function tests; SIADH, syndrome of inappropriate secretion of antidiuretic hormone; URI, upper respiratory infection; CNS, central nervous system; bid, twice daily; tid, three times daily; qid, four times daily.

Most adult patients (85%) present with the classic triad of fever, headache, and neck stiffness (Roos et al., 1997). Other symptoms include nausea and vomiting (35%), seizures (30%), cranial nerve palsies, and other focal neurologic signs (10%-20%). Meningismus (50%) may be subtle or marked, as with Kernig’s sign (resistance to knee extension after flexion of hip and knees by examiner) or Brudzinski’s sign 976

(involuntary flexion of knees in supine patient in response to rapid neck flexion by examiner) (Tunkel and Scheld, 1997). Other symptoms include nuchal rigidity, lethargy, photophobia, confusion, sweats, and rigors. Papilledema occurs in less than 1% of patients during the early phases of the disease. When papilledema is present early, an alternative diagnosis such as a brain abscess or mass lesion should be sought.

Neurology

Box 42-8 Drugs that Can Lower Seizure Threshold Theophylline Isoniazid Tricyclic antidepressants Penicillin Phenothiazines Diphenhydramine Pseudoephedrine Cocaine Amphetamines Alcohol (withdrawal) Benzodiazepines Barbiturates (including phenobarbital)

Not all patients present with the classic signs and symptoms. Neonates may present with poor feeding or weak sucking response, irritability, vomiting, temperature instability (hyperthermia or hypothermia), diarrhea, and apnea. Nuchal rigidity and meningismus are not reliable signs in children younger than 1 year (Prober, 1996). A bulging fontanelle may occur late in the disease, and seizures occur in 40% of neonates. A maculopapular rash that later becomes petechial and purpuric on the extremities should suggest meningococcal meningitis. Older-adult patients may have a more insidious presentation, with variable meningeal signs, change in mental status, lethargy, obtundation, and no fever. The host is an important determinant of susceptibility to meningitis. Obvious risk factors include a history of recent open trauma, surgery (especially neurosurgery), and burns. Closed-head trauma can cause cerebrospinal fluid (CSF) leaks, which have been associated with pneumococcal meningitis. Common predisposing factors include otitis media (most common), sinusitis, mastoiditis, alcoholism, perinatal exposure, and nonimmunized, immunocompromised, or asplenic status (Swartz, 1997). Knowing the most prevalent organisms that cause bacterial meningitis in the various age groups is important in guiding empiric therapeutic choices (Table 42-6). The three most common pathogens for community-acquired bacterial meningitis are Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, accounting for about 80% of cases in the United States. Until the development of the H. influenzae type b (Hib) vaccine in the early 1990s, this was the most common bacterial meningitis, occurring in almost 50% of cases. As a result, S. pneumoniae and N. meningitidis have become relatively more common, especially in the pediatric population. Escherichia coli has been superseded by group B streptococci as the most common cause in infants during the first months of life. Other common pathogens include Listeria monocytogenes, Klebsiella pneumoniae, Staphylococcus aureus and S. epidermidis, other gram-negative bacilli, and other streptococci.

Initial Management The Infectious Disease Society of America (IDSA) practice guidelines call for prompt blood cultures and lumbar puncture for most patients with suspected acute bacterial meningitis (Tunkel et al., 2004). Nevertheless, emergency LP may not be successful or prudent because of overriding

Table 42-6 Common Pathogens of Bacterial Meningitis Based on Age

Age

Pathogens

0-1 mo

Group B streptococcus, Listeria monocytogenes, Escherichia coli, Streptococcus pneumoniae

1-3 mo

Group B streptococcus, E. coli, L. monocytogenes, S. pneumoniae, Neisseria meningitidis, Haemophilus influenza

3 mo-18 yr

H. influenzae, N. meningitidis, S. pneumoniae

18-50 yr

H. influenzae, N. meningitidis, S. pneumoniae

>50 yr

S. pneumoniae, L. monocytogenes, gram-negative bacilli

Table 42-7 Criteria for Adult Patients with Suspected Bacterial Meningitis Recommended for CT before LP

Criterion

Comment

Immunocompromised state

HIV infection or AIDS, receiving immunosuppressive therapy, or after transplantation

History of CNS disease

Mass lesion, stroke, or focal infection

New-onset seizure

Within 1 week of presentation; some authorities would not perform LP on patients with prolonged seizures or would delay LP for 30 minutes in patients with short, convulsive seizures.

Papilledema

Presence of venous pulsations suggests absence of increased intracranial pressure.

Abnormal level of consciousness

—

Focal neurologic deficit

Includes dilated nonreactive pupil, abnormalities of ocular motility, abnormal visual fields, gaze palsy, arm or leg drift.

From Tunkel AR, Barry J, Hartman SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267. CT, Computed tomography; LP, lumbar puncture; HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome; CNS, central nervous system.

c oncerns about a CNS mass lesion or other cause of increased ICP, necessitating CT before LP. In these patients, blood samples should be drawn and appropriate antibiotic and adjunctive therapy provided before LP or CT (Table 42-7). The LP is the foundation of the diagnosis of bacterial meningitis. In adults, opening pressure is typically 200 to 500 mm H2O, although lower values may be observed in infants and children. Table 42-8 illustrates typical CSF findings. Gram stain is recommended for all patients, because it permits rapid organism identification in 60% to 90% of patients with community-acquired bacterial meningitis, with a specificity of more than 97% (Tunkel et al., 2004). Other rapid diagnostic tests, such as latex agglutination, and limulus lysate assay have not shown clinical usefulness in diagnosis 977

42

Neurology

Table 42-8 Typical Cerebrospinal Fluid Findings in Bacterial and Viral Meningitides

Parameter

Bacterial Meningitis

Table 42-9 Antimicrobial Therapy in Adult Patients with Presumptive Pathogen Identification by Positive Gram Stain

Viral Meningitis

Microorganism

Recommended Therapy

Alternative Therapies

Opening pressure (mm H2O)

>180

Often normal or significantly elevated

Streptococcus pneumoniae

Meropenem (C), fluoroquinolone‡ (B)

Leukocyte count (cells/mm3)

1000-10,000 Median: 1195 Range: 100-20,000

80

450 mg total dose) help reduce the risk of unsatisfactory recovery from Bell’s palsy (de Almeida et al., 2009) (SOR: A).

994

Trigeminal Neuralgia Trigeminal neuralgia (tic douloureux) usually involves the second and third (maxillary and mandibular) divisions of the trigeminal nerve, causing pain of the innervated structures (lips, gums, teeth). It is almost always unilateral, with the pain sudden, sharp, and severe, lasting a few seconds at a time. This cycle of pain can occur hundreds of times a day. It may be described as lancinating, ice pick like, or an electric shock and characteristically is precipitated by innocuous stimuli such as light touch to the face or toothbrushing. It is rarely seen in patients younger than 40. Pain that is longer in duration, bilateral, or described as more aching or pressure like is usually not related to trigeminal neuralgia and should cause the physician to search for another cause. Other conditions that should be considered include multiple sclerosis, acoustic neurinoma, aneurysm, meningioma, trigeminal neuroma, and early herpes zoster or postherpetic neuralgia. Herpes zoster should be suspected in patients younger than 40 who present with pain following the upper division of the trigeminal nerve (forehead and eye). Neuroimaging with MRI scanning of the brain is recommended to exclude these causes from idiopathic disease. A common initial pharmacologic treatment for idiopathic trigeminal neuralgia is carbamazepine (Tegretol), up to 800 mg/day, or oxcarbazepine (Trileptal), up to 1200 mg/ day. Usually, these medications are started at relatively low doses (100-200 mg once or twice daily) and increased at 7- to 10-day intervals until adequate symptom control is achieved. Patients should be educated that these medicines will only work when taken on a consistent basis and not as an analgesic medication. Other medications that have been used but are not FDA approved include gabapentin (Neurontin), amitriptyline, and baclofen. Toxicities from these medications, including allergic reactions, bone marrow suppression, and liver toxicity, may develop and thus require close monitoring. Patients with refractory symptoms or who do not tolerate pharmacologic treatment should be considered for neurosurgical evaluation.

Parkinson’s Disease Key Points • T he hallmark clinical features of Parkinson’s disease include resting tremor, rigidity and bradykinesia of asymmetric onset. • Symptoms such as hallucinations, gait abnormalities, paralysis of upward gaze, early dementia, early postural instability, early autonomic dysfunction, involuntary movements other than a tremor and a failure to respond to levodopa suggest a parkinsonism-plus syndrome and require further evaluation. • Drug therapy for Parkinson’s disease should be initiated when the symptoms are significant enough to cause functional impairment.

Parkinson’s disease is the second most common progressive neurodegenerative disorder in the United States after Alzheimer’s disease. Parkinson’s affects about 1% of the population over age 60 and 4% to 5% of those older than 85. The disease is uncommon before age 40, and incidence is higher in men than women. A genetic predisposition to Parkinson’s disease may be present; up to 15% of patients will have a first- or second-degree relative with Parkinson’s

Neurology

disease. At present, no clear environmental links to Parkinson’s disease have been identified. The disease is caused by a disruption of dopaminergic neurotransmission in the basal ganglia and the development of eosinophilic intracytoplasmic inclusions (Lewy bodies) in the residual dopaminergic neurons.

Symptoms and Signs The hallmark clinical features of Parkinson’s disease include tremor, rigidity, and bradykinesia, usually of asymmetric onset. Tremor is the presenting symptom in up to 70% of patients, and in fact, an asymmetric rest tremor is virtually pathognomonic of Parkinson’s disease. Many patients pre sent to the family physician complaining of a tremor and the concern they may have Parkinson’s disease. Most will have essential tremor, which can be differentiated from the tremor of Parkinson’s disease in that essential tremor is usually symmetric and exacerbated by action, whereas the tremor of Parkinson’s disease is usually at rest and asymmetric. Rigidity is often associated with cogwheeling, a ratchety quality during passive movement of the limb. Bradykinesia refers to the slowness of movements, which usually begins in an asymmetric fashion, described by the patient as “weakness” of an extremity, although no abnormalities are noted with strength testing. Other clinical features associated with Parkinson’s disease include micrographia, paucity of facial expression (masked facies), narrow shuffling gait, and postural instability (late finding). Behavioral and cognitive symptoms are frequently seen in patients with Parkinson’s disease as well.

Differential Diagnosis Up to 20% of patients initially diagnosed with Parkinson’s disease ultimately have an alternative diagnosis. The term parkinsonism-plus syndrome is used for patients who have similar symptoms but also have additional abnormalities or do not respond to the usual medications. Symptoms that suggest a parkinsonism-plus syndrome include hallucinations, gait abnormalities, paralysis of upward gaze, early dementia, early postural instability, early autonomic dysfunction, involuntary movements other than tremor, and a failure to respond to levodopa (Italian Neurological Society, 2003). Conditions that frequently may be confused with Parkinson’s disease include progressive supranuclear palsy, dementia with Lewy bodies, multiple-system atrophy, vascular parkinsonism, and drug-induced parkinsonism. Progressive supranuclear palsy (PSP) may initially be mistaken for Parkinson’s disease. Patients have ophthalmoparesis of vertical gaze, primarily downward gaze. Early loss of postural reflexes, predominantly axial rigidity, pseudobulbar palsy, and frontal lobe signs are other characteristics of PSP. Response to dopaminergic medications is minimal. Dementia with Lewy bodies has motor symptoms similar to those of Parkinson’s disease, and there may be a response to levodopa. Rigidity is usually more prominent than bradykinesia or tremor. Additionally, there is early cognitive impairment and hallucinations early in the disease course. Multisystem atrophy includes a number of diseases, and it is not clear if they represent distinct diseases or a single, pathologic continuum. This group includes olivopontocerebellar atrophy, striatonigral degeneration, and Shy-Drager syndrome.

Symptoms are related to autonomic nervous system dysfunction and include orthostatic hypotension, cerebellar dysfunction, bladder dysfunction, and a poor levodopa response. Vascular parkinsonism may be associated with multiple vascular lesions in the basal ganglia. There is usually a stepwise progression to the disease. Tremor at rest is not a common finding, and the bradykinesia and rigidity tend to be more significant in the legs. The gait is often broad based. Associated symptoms include dementia, spasticity, and weakness. MRI studies show multi-infarct changes, and the response to levodopa is poor. A final category of Parkinson-like conditions is drug-induced parkinsonism. It is important to identify this cause because it is usually reversible. Drug-induced parkinsonism accounted for 20% of cases of parkinsonism-plus conditions in a population-based study (Bower et al., 1999). Medications that can cause these symptoms include neuroleptics, atypical neuroleptics, antiemetic medications (e.g., metoclopramide, prochlorperazine), amiodarone, valproic acid, and lithium. Medicines that block the synthesis of dopamine, such as methyldopa (Aldomet), or deplete dopamine (e.g., reserpine), can also induce parkinsonism (Nutt and Wooten, 2005).

Diagnostic Evaluation An extensive diagnostic evaluation is not necessary when the history and physical examination reveal classic findings of Parkinson’s disease. Imaging of the brain with CT or MRI may be performed if the diagnosis is in question and to rule out other conditions such as NPH or vascular parkinsonism. Consultation with a neurologist may be helpful, especially if the diagnosis is in question or a parkinsonism-plus diagnosis is likely.

Treatment Currently, diagnosis of Parkinson’s disease does not relegate a patient to pharmacologic treatment. Drug therapy should be initiated when the symptoms are significant enough to cause functional impairment (Rao et al., 2006). Current therapies do not appear to slow the progression of the disease and no studies have clearly demonstrated a best initial treatment for this condition (Schreck et al., 2003). Table 42-17 summarizes the pharmacologic agents available to treat Parkinson’s disease.

Pharmacotherapy Levodopa, a precursor of dopamine, is the most frequently prescribed agent for the treatment of symptomatic Parkinson’s disease and is particularly effective at controlling bradykinesia and rigidity (Miyasaki et al., 2002). Alone, levodopa is absorbed but is peripherally metabolized to dopamine by dopa-decarboxylase enzymes. This peripheral conversion limits the overall effectiveness of levodopa and increases the side effects, including nausea, vomiting, and hypotension. To remedy this, levodopa is combined with carbidopa, which prevents this peripheral conversion. Dopa-decarboxylase is saturated with 70 to 100 mg of carbidopa. Thus the usual starting dose of carbidopa-levodopa is 25 mg/100 mg three times daily (Rao et al., 2006). Dopamine agonists directly stimulate dopamine receptors, thus bypassing the presynaptic synthesis of dopamine. These medications cause less dyskinesia and fewer fluctuations 995

42

Neurology

Table 42-17 Medications for Parkinson’s Disease

Generic Name

Recommended Dosage

Side Effects/Comments

Trihexyphenidyl (Artane)

1 mg tid; increase to 2 mg tid

Effective for tremor. Side effects include impaired memory, blurred vision, and urinary retention.

Benztropine (Cogentin)

0.5 mg at bedtime; increase by 0.5 mg up to max 1 mg bid.

Same as for trihexyphenidyl.

Anticholinergics

Carbidopa-Levodopa Combinations Immediate release (Sinemet)

25 mg/100 mg initially ½ tablet tid; increase by ½ tablet every 4-7 days.

“Gold standard” of therapy. Long-term therapy may result in motor fluctuations, dyskinesias, confusion, and hallucinations.

Controlled release (Sinemet-CR)

1 tablet bid

Same as for immediate release.

Carbidopa-levodopa plus entacapone (Stalevo)

1 tablet tid

Same as for other carbidopa-levodopa preparations, plus diarrhea.

Catechol-O-Methyltransferase (COMT) Inhibitors Tolcapone (Tasmar)

100 mg or 200 mg tid

Adjunct to levodopa to prevent motor fluctuations. Monitor liver functions.

Entacapone (Comtan)

200 mg with each dose of carbidopa-levodopa, up to 8 times daily

Same as for tolcapone.

Bromocriptine (Parlodel)

1.25 mg with meals bid; increase by 2.5 mg every 2-4 weeks to max 15 mg/day.

Effective in monotherapy or as adjunct to levodopa.

Pramipexole (Mirapex)

0.125 mg tid, max 1.5 mg tid

Side effects include excessive daytime somnolence, hypotension, confusion, and hallucinations.

Ropinirole (ReQuip)

25 mg tid; increase weekly by 0.25 mg tid to 3 mg tid. Max dose 8 mg tid

Same as for pramipexole.

Dopamine Agonists

Monoamine Oxidase Type B (MAO-B) Inhibitors Selegiline (Eldepryl)

5 mg at breakfast and lunch

Avoid use with SSRIs, TCAs, and meperidine. Side effects include nausea, dizziness, hallucinations, abdominal pain, and vivid dreams.

Rasagiline (Azilect)

0.5 mg/day to 1 mg/day

Side effects include extrapyramidal symptoms, dyskinesia, hallucinations, hypotension, and depression.

N-Methyl-d-Aspartate (NMDA) Antagonist (Receptor Inhibitor) Amantadine (Symmetrel)

100 mg twice daily

May be used as monotherapy Side effects include dizziness, confusion, livedo reticularis, and hallucinations.

bid, Twice daily; tid, three times daily; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants.

than levodopa. They can be used alone or in conjunction with levodopa. Currently, bromocriptine (Parlodel), pramipexole (Mirapex), and ropinirole (ReQuip) are medications in this class available for the treatment of Parkinson’s disease. Apomorphine (Apokyn) is also available as a subcutaneous injection for the treatment of sudden, resistant “off” periods (Goetz et al., 2005). It has significant adverse effects and should only be used by individuals experienced with its use. Dopamine agonists should not be used in patients with 996

dementia because of the high likelihood of producing hallucinations (Nutt and Wooten, 2005). Monoamine oxidase type B (MAO-B) inhibitors were initially thought to provide a neuroprotective effect to patients with Parkinson’s disease. This has not been supported in the literature. Agents available in the United States in this class include selegiline (Eldepryl), orally disintegrating selegiline (Zelapar), and rasagiline (Azilect). A meta-analysis of 17 trials comparing MAO-B inhibitors with placebo or levodopa

Neurology

revealed MAOIs reduce disability, incidence of motor fluctuations, and need for levodopa (Ives et al., 2004). Anticholinergic medications primarily work on the muscarinic acetylcholine receptors. These medications have low effectiveness and a high incidence of side effects which limit their overall usefulness to patients younger than 70 years and with preserved cognitive function. Degradation of levodopa in the periphery is known to be associated with motor fluctuations and dyskinesia in Parkinson’s disease. The enzyme catechol-O-methyltransferase (COMT) is responsible for part of this degradation. COMT inhibitors prolong the dopamine response. Two medications in this category are tolcapone (Tasmar) and entacapone (Comtan). These medications reduced “off” time, reduced total levodopa dose, and improved motor symptoms in patients with advanced Parkinson’s disease and motor complications (Cochrane review; Deane et al., 2004). As such, COMT inhibitors are usually reserved for more advanced cases. Among NMDA antagonists (NMDA receptor inhibitors), amantadine (Symmetrel), originally developed as an antiviral agent, is useful for tremor, rigidity, and bradykinesia associated with Parkinson’s disease, although few studies demonstrate its clear efficacy. Amantadine may also have a dopamine agonist effect as well as an anticholinergic effect. Side effects include dizziness, insomnia, nausea, and vomiting.

Surgical Treatment Surgical treatments are options to be considered when tremor, motor fluctuations, and dyskinesia are not adequately controlled with medications alone. Techniques that offer potential benefit include unilateral pallidotomy and deep brain stimulation of the globus pallidus interna or subthalamic nucleus (Goetz et al., 2005). Patients with symptoms not controlled medically should be referred to specialized centers with surgeons experienced in performing these procedures.

Treatment of Nonmotor Symptoms Patients with Parkinson’s disease frequently develop other comorbid conditions such as depression or dementia. In the case of depression, an SSRI can be used. Up to 40% of patients develop dementia (Aarsland et al., 2003). In these patients the cholinesterase inhibitors can be effective. Parkinson’s disease is a progressive illness, so it is important for the family physician to discuss advanced directives, establishment of power of attorney for health care decisions, and the patient’s wishes surrounding the use of artificial nutrition. Living wills and other legal documents should be prepared and appropriate discussions documented. Common symptoms such as constipation, sleep disturbance, and orthostatic hypotension should be aggressively treated.

KEY TREATMENT Levodopa, dopamine agonists, and MAO-B inhibitors, alone or in combination, are effective in treating the symptoms of Parkinson’s disease (Rao et al., 2006) (SOR: A). Usual starting dose of carbidopa-levodopa is 25 mg/100 mg three times daily (Rao et al., 2006) (SOR: A). Surgical therapies (unilateral pallidotomy, deep brain stimulation) are effective when medical therapy fails to control Parkinson symptoms (Goetz et al., 2005) (SOR: B).

Multiple Sclerosis Key Points • T he diagnosis of multiple sclerosis requires evidence of demyelinating disseminated disease. • Optic neuritis, nystagmus from internuclear ophthalmoplegia, and Lhermitte’s sign are highly suggestive of MS. • The currently most widely accepted diagnostic criteria for MS are the McDonald criteria, established by an international panel in 2001 and revised in 2005.

Multiple sclerosis (MS) is a recurrent, chronic, demyelinating, autoimmune disorder that affects the central nervous system. The mean age of onset for MS is 29 to 33 years, although the range is 15 to 50 years, which makes this the most common cause of neurologic disability in young adults.

Diagnosis The diagnosis of MS is based on clinical signs and symptoms combined with diagnostic testing, which may include MRI, CSF analysis, and visual-evoked potentials (VEPs). Definitive diagnosis of MS requires evidence of demyelinating disease disseminated over time and space (McDonald et al., 2001). That is, clinical symptoms should last at least 24 hours and should be separated by at least 30 days, and should affect two different areas of the CNS: the brain, spinal cord, or optic nerves. The clinical symptoms vary, depending on which part of the CNS is involved. Three symptoms are highly suggestive of MS: optic neuritis, nystagmus resulting from internuclear ophthalmoplegia, and Lhermitte’s sign, which is an electrical sensation extending down the back and legs with flexion of the neck. The International Panel of the Diagnosis of Multiple Sclerosis developed criteria for the diagnosis of MS (McDonald et al., 2001), revised in 2005 and summarized in Table 42-18 (Polman et al., 2005). It is important to remember that alternative diagnoses should be considered and excluded. These would include CNS vasculitis, paraneoplastic syndromes, sarcoidosis, leukodystrophies, CNS tumors, infections, CNS lymphoma, and nutritional deficiencies, such as B12 deficiency. The precise relationship between clinical symptoms and MR findings are not well understood. Thus, MRI alone is not useful in predicting the clinical course of MS. T2-weighted MR images best define the size of white matter lesions, and gadolinium can reveal the disruption of the blood-brain barrier associated with an active MS lesion. In general, MR findings consistent with MS must include at least three of these findings: (1) one gadolinium-enhancing lesion or nine T2 hyperintense lesions if gadolinium-enhancing lesions are not present; (2) at least one infratentorial lesion; (3) at least one juxtacortical lesion; and (4) at least three periventricular lesions. These lesions should be at least 3 mm in cross section (Barkof et al., 1997; Tintore et al., 2000). Spinal cord lesions can be substituted for one of the brain lesions as long as it reveals little or no swelling of the spinal cord, is unequivocally hyperintense if detected with T2-weighted MR images, at least 3 mm in size but less than two vertebral segments in length, and occupies only part of the cross section of the spinal cord (Polman et al., 2005). 997

42

Neurology

Table 42-18 Criteria for Multiple Sclerosis (MS)

Clinical Presentation

Additional Data Needed

Two or more attacks (relapses); two or more objective clinical lesions

None; clinical evidence will suffice (additional evidence desirable but must be consistent with MS)

Two or more attacks; one objective clinical lesion

Dissemination in space, demonstrated by MRI or Positive CSF and two or more MRI lesions consistent with MS or further clinical attack involving different site

One attack; two or more objective clinical lesions

Dissemination in time, demonstrated by MRI or second clinical attack

One attack; one objective clinical lesion (monosymptomatic presentation)

Dissemination in space by demonstrated by MRI or Positive CSF and two or more MRI lesions consistent with MS and Dissemination in time demonstrated by MRI or Second clinical attack

Insidious neurologic progression suggestive of MS (primary progressive MS)

Positive CSF and Dissemination in space demonstrated by MRI evidence of nine or more T2 brain lesions or Two or more spinal cord lesions or Four to eight brain and one spinal cord lesion or Positive VEP with four to eight MRI lesions or Positive VEP with less than four brain lesions and one spinal cord lesion and Dissemination in time demonstrated by MRI or Continued progression for 1 year

Modified from McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 200;150:121. MRI, Magnetic resonance imaging; CSF, cerebrospinal fluid; VEP, visual-evoked potential.

The CSF analysis of patients with MS generally demonstrates a normal opening pressure, cell count, glucose level, protein level, and culture. The most clinically useful CSF abnormality is the presence of oligoclonal immunoglobulin G (IgG) bands resulting from intrathecal IgG synthesis, which can be found in up to 90% of patients with MS (Freedman et al., 2005). IgG bands are not specific to MS and are also seen in sarcoidosis, AIDS, and subacute sclerosis panencephalitis. The value of CSF analysis is mainly limited to MS patients with only a few lesions on MRI, or to make the diagnosis of primary progressive MS, as discussed later. Visual-evoked responses may also provide supporting evidence for MS, particularly in situations with few abnormalities on MRI. Other VEP analysis offers little in establishing a diagnosis of MS (Gronseth and Ashman, 2000).

Clinical Course Four subtypes of MS are currently described—relapsing remitting, secondary-progressive, primary progressive, and progressive-relapsing. Relapsing-remitting MS accounts for about 85% of the initial diagnosis of MS patients and is characterized by acute attacks followed by full recovery. The interval between relapses can be variable and is characterized by a lack of disease progression. Secondary-progressive MS is characterized by a pattern that is initially relapsingremitting but then evolves into a pattern of progressive neurologic decline. MRI demonstrates more extensive lesions, and approximately 50% of patients initially diagnosed with relapsing-remitting MS will develop secondary-progressive disease. Primary-progressive MS, characterized by a gradual disease progression from the initial onset, accounts for approximately 10% of MS diagnoses and has limited 998

t reatment options. Progressive-relapsing MS demonstrates a pattern of steady progression from the time of onset that may be punctuated by clearly defined relapses. The patients may or may not fully recover from these acute relapses.

Treatment The treatment of MS can be divided into disease-modifying therapies, medications for acute relapses, and symptomatic management. Although there is no definitive cure, diseasemodifying therapies may reduce the frequency of relapses, slow the rate of progression, and reduce the acute inflammatory response. Symptomatic therapy can improve the control of many of the functional disabilities and thus improve quality of life.

Disease-Modifying Therapies It is generally held that disease-modifying therapy should be initiated immediately on the diagnosis of MS (Coyle and Hartung, 2002). Disease-modifying therapy has been shown to be more effective in preventing new lesion formation than repairing old lesions. These therapies include interferon beta-1b (Betaseron), interferon beta-1a (Avonex, Rebif), and glatiramer acetate (Copaxone). The beta interferons are immunomodulating medications that also have antiviral activities. They have been shown to reduce relapses in patients with the relapsing-remitting form of MS. Betaseron is given as an alternating-day subcutaneous (SC) injection, Rebif is a three-times-weekly SC injection, and Avonex is administered as a weekly intramuscular injection. All have similar side effects, including injection site reactions, influenza-like symptoms, and worsening of preexisting depression. Bone marrow suppression and transient elevation of liver enzymes may also occur.

Neurology

Glatiramer (Copaxone) is a synthetic polypeptide consisting of four amino acids. It is thought to lead to the induction of antigen-specific suppressor T cells. It is administered as a daily SC injection and has been shown to reduce relapses by approximately 30% (Comi et al., 2001). Side effects include postinjection reactions and occasionally a reaction involving flushing, chest pain, anxiety, and dyspnea. The reaction is self-limited and does not require discontinuation of the medication. Two other disease-modifying drugs for MS are mitoxantrone and natalizumab. Mitoxantrone is a synthetic anthracenedione given by IV infusion once every 3 months. It has been shown to reduce MS relapses by 67% (Hartung et al., 2002). Mitoxantrone is blue and can lead to transient bluish discoloration of the sclera and urine. It also can cause cardiotoxicity, and as a chemotherapeutic agent, should only be prescribed for worsening cases of MS not responding to firstline agents. Also, only experienced health care professionals should prescribe mitoxantrone. Natalizumab is a monoclonal antibody that blocks α4integrin. This molecule is involved in moving circulating leukocytes into the brain in response to inflammation. It is administered as a 1-hour infusion every 4 weeks. Natalizumab has been shown to reduce clinical relapses, slow the progression of disability, and reduce the development of new brain lesions (Polman et al., 2006). Complications that limit its use include a hypersensitivity reaction up to an hour after infusion. Natalizumab has also been associated with progressive multifocal leukoencephalopathy, a destructive brain infection caused by JC virus. Therefore the distribution and use of natalizumab is closely monitored, and it can be administered only by registered physicians.

Medications for Acute Relapses Glucocorticoids are still widely used for the treatment of acute exacerbations of MS. The principal effects of corticosteroids appear to be related to their anti-inflammatory and

antiedema effects. It is recommended as standard therapy for any patient with an acute attack of MS (Goodin et al., 2002). Treatment normally consists of 3 to 5 days of a 1-g/day IV infusion of methylprednisolone. Oral prednisone taper may or may not be used after infusion.

Symptomatic Management Medications used for symptomatic management depend on the specific symptoms encountered by the patient. MS patients frequently develop spasticity, which can be treated with baclofen, tizanidine, or benzodiazepines. Physical therapy can also help with spasticity. Bladder dysfunction can also occur in patients with MS. New bladder symptoms should be evaluated with a urine culture to rule out infection. A postvoid residual should also be obtained, as well as urodynamic testing to determine whether the problem is overflow incontinence from urinary retention or urge incontinence from detrusor instability. In the presence of urge incontinence, the anticholinergics oxybutynin (Ditropan) and tolterodine (Detrol) may be useful. If the problem is urinary retention and overflow incontinence, patients will usually need to be treated with intermittent self-catheterization. Patient may also experience depression, constipation, and sexual dysfunction. The usual evaluation and treatment options should be considered for patients who experience these problems.

KEY TREATMENT Beta interferons have been shown to reduce the number of relapse in patients with the relapsing remitting form of MS (Coyle and Hartung, 2002) (SOR: A). Glucocorticoids are recommended as standard therapy for any patient with an acute attack of MS (Goodin et al., 2002) (SOR: A). Disease-modifying therapy should begin at diagnosis of MS (Coyle and Hartung, 2002) (SOR: B).


Web Resources http://neuromuscular.wustl.edu/ Washington University Neuromuscular Disease Center; comprehensive resource for disorders affecting peripheral nerve, muscle, and neuromuscular junction. www.cdc.gov/vaccines/recs/schedules/child-schedule.htm Centers for Disease Control and Prevention recommended immunization schedule. www.aan.com American Academy of Neurology practice parameters and neurologic news.

www.wemove.org/ WE MOVE; resource for both patients and practitioners concerning movement disorders. www.strokecenter.org/trials/ Internet Stroke Center–Stroke Trials; updated resource for ongoing and completed trials related to stroke.

999

43 CHAP T E R Medical Human Sexuality Wendy S. Biggs

Chapter contents Overview Sexual Self-Concept Models of Human Sexual Response Initial Evaluation of Sexual Problems

Female Sexual Dysfunction Hypoactive Sexual Desire Disorder Female Sexual Arousal Disorder Female Orgasmic Disorder Sexual Pain Disorders

1000 1000 1000 1000

1002 1002 1003 1003 1004

Male Sexual Dysfunction

1005

Erectile Dysfunction Premature (Rapid) Ejaculation

1005 1007

Overview Sexuality is a fundamental aspect of human self-concept and a complex biopsychosocial process. Physiologic aspects of sexuality are interpreted within the patient’s cultural and social context. Family physicians and primary care providers are well situated to offer patients basic information regarding human sexual health issues and to evaluate and treat most common sexual problems; however, they seldom ask patients about sexual functioning. This chapter describes the basic principles of evaluation of female and male sexual dysfunction and clinical management of common disorders.

Sexual Self-Concept Humans possess a gender identity and a sexual orientation. Gender, in many Western cultures, is synonymous with their chromosomal or genital phenotype (male or female sex). Gender identity, however, is a more comprehensive internal self-perception of being male or female, masculine or feminine. Many cultures, including Native American and African groups, do not regard gender as being determined by sex characteristics, and these cultures may provide an accepted role for persons in whom these aspects are not congruent. Sexual orientation may be defined as the attraction individuals feel toward sexual partners of their own or the other gender. Sexual orientation is self-defined, and individuals may describe themselves at different points in their lifetime as exclusively attracted to their own gender (homosexuality) or the opposite gender (heterosexuality), or somewhere between these two (bisexuality). ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10043-0

Male Orgasmic Disorder Dyspareunia

Sexual Orientation Spectrum

1008 1008

1008

Clinical Considerations in the Care of Lesbian, Gay, and Bisexual Patients 1008 Spectrum of Gender Identity and Expression 1008 Transgender Health Care 1009

Sexuality Issues at Specific Times of Life

1009

Adolescence Older Adults

1009 1011

Conclusion

1012

Models of Human Sexual Response Masters and Johnson first described the physiology of “human sexual response cycle” in 1966. Based on the physical components of sexual functioning, they described four phases of the sexual response cycle: excitement, plateau, orgasm, and resolution (Fig. 43-1). Helen Singer Kaplan subsequently described a more subjective, psychologically oriented sexual responsiveness model with three phases: desire, excitement, and orgasm. Recently, however, nonlinear alternative models have been suggested, especially for women’s sexual response (Basson and Schultz, 2007) (Fig. 43-2). In certain settings, men may have similar nonlinear sexual responses. Response phases establish a framework to discuss sexual dysfunction.

Initial Evaluation of Sexual Problems Many patients would benefit from detection and treatment of sexual problems; however, many clinicians do not ask, and patients may not volunteer the information. In the Global Study of Sexual Attitudes and Behaviors, which surveyed more than 27,000 adults age 40 to 80 in 29 countries, 49% of women and 43% of men reported experiencing at least one sexual problem; fewer than 20% had sought medical assistance for sexual issues (Moreira et al., 2005). Health care providers should proactively and routinely address sexual health. The sexual health interview may be approached with a screening or abbreviated method, followed by in-depth questioning, if necessary (Nusbaum and Hamilton, 2002) (Box 43-1). The answers on the detailed sexual history then

Medical Human Sexuality

direct the physical examination and appropriate laboratory testing. A physician may open the sexual history questioning with an inclusion technique: “Sexual health is important to overall health, therefore, I ask all my patients about it. I’m going to ask you a few questions on sexual matters now.”

Orgasm

Plateau Re

so

tion solu

ABC

lut

Re

A

Resolution

Excitement

ion

B

A

C

Orgasm Plateau

Re tion solu

B

tion solu

Refractory period

Re

Excitement

Refractory period

Figure 43-1 Female (A) and male (B) sexual response cycles. Desire precedes both cycles in this model. The phases illustrated are excitement, plateau, and orgasm. The length of the plateau phase is variable. Women may have a brief plateau followed by orgasm (cycle C) or a long plateau with no orgasm (cycle B). Women may have multiple orgasms before resolution, although many do not (cycle A). For men with premature ejaculation, the plateau phase is brief. After ejaculation, men enter a refractory period lasting minutes to hours during which they are unable to ejaculate.

The clinician can use normalization or universalization techniques. In normalization the clinician introduces emotionally laden or difficult subjects by implying these experiences are quite prevalent: “Many people have been sexually abused or molested as children. Did you have any experiences like that when you were young?” Universalization phrases questions as if everyone has done everything, making an affirmative answer easier for sensitive questions. For example, patients may be asked “How often do you masturbate?” instead of “Do you masturbate?” The clinician should also reassure the patient about physician-patient confidentiality. Jack Annon in 1976 proposed the PLISSIT model to approach sexual concerns: Permission, Limited Information, Specific Suggestions, and Intensive Treatment (Box 43-2). The clinician can alternatively use the ALLOW acronym: Ask, Legitimize, Limitations, Open up, and Work together (Hatzichristou et al., 2004), as discussed next. Ask. Questions regarding sexual functioning should be asked in a matter-of-fact yet sensitive manner. Physicians should avoid terms that make assumptions regarding patients’ sexual behaviors. When inquiring about past or recent sexual encounters, the clinician may inquire “with men, women, or both?” Using the term “partner” instead of “husband” or “boyfriend” or “wife” or “girlfriend” may allow patients to discuss their sexual orientation openly. Slang words should be redefined in medical terminology so that the clinician and patient may communicate clearly. Legitimize. By acknowledging the clinical relevance of sexual dysfunction, the clinician legitimizes the patient’s sexual problem. Opening questions also can be linked to the patient’s medical problems: “Many people with hypertension and heart disease notice a change in sexual functioning. Have you noticed any change?” Limitations. The patient’s knowledge may have limitations, and patient education may address the patient’s perceived sexual dysfunction. For example, an older man with longer time between erections may not know the refractory period normally increases with age. Patient education and

Multiple motivations

Other rewards, e.g., emotional intimacy, increased well-being

INITIAL SEXUAL DESIRE (variable)

Deliberate attention to stimuli

Biological factors Sexual satisfaction and absence of pain Processing of stimuli

Arousal triggers desire

Subjective arousal and autonomic nervous system response

Psychological factors

Figure 43-2 Circular model of female sexual response showing cycle of overlapping phases. (From Basson R, Schultz WW. Sexual sequelae of general medical disorders. Lancet 2007;369:409-424.

1001

43


r eassurance may eliminate his perceived “sexual dysfunction.” Physicians should recognize their own limitations and, if necessary, refer a patient to the appropriate specialist for further evaluation and treatment of a sexual dysfunction. Open up, for further discussion and evaluation. A detailed sexual history may be needed to evaluate fully a patient’s

Box 43-1 Questions for a Detailed Sexual History Are you currently sexually active? Have you ever been sexually active? Are your sexual partners men, women, or both? How many sexual partners have you had in the past month? Past 6 months? Lifetime? How satisfied are you with your (and/or your partner’s) sexual functioning? Has there been any change in your (or your partner’s) sexual desire or the frequency of sexual activity? Do you have, or have you ever had, any risk factors for HIV (blood transfusion, needle stick injuries, IV drug use, STIs, partners who placed you at risk)? Have you ever had any sexually related diseases? Have you ever been tested for HIV? Would you like to be? What do you do to protect yourself from contracting HIV? What method do you use for contraception? Are you trying to become pregnant (or father a child)? Do you participate in oral sex? Anal sex? Do you or your partner(s) use any particular devices or substances to enhance your sexual pleasure? Do you ever have pain with intercourse? Women: Do you have any difficulty achieving orgasm? Men: Do you have any difficulty obtaining and maintaining an erection? Difficulty with ejaculation? Do you have any questions or concerns about your sexual functioning? Is there anything about your (or your partner’s) sexual activity (as individuals or as a couple) that you would like to change? From Nusbaum MRH, Hamilton CD. The proactive sexual health history. Am Fam Physician 2002;66:1705-1712. HIV, Human immunodeficiency virus; STIs, sexually transmitted infections; IV, intravenous.

Box 43-2 PLISSIT Model for Approaching Sexual Problems Permission For physician to discuss sex with the patient. For the patient to discuss concerns now or in the future. To continue sexual behaviors not potentially harmful. Limited Information Clarify misinformation. Dispel myths. Provide factual information in a limited manner. Specific Suggestions Provide specific suggestion directly related to the particular problem. Intensive Treatment Provide highly individualized therapy for more complex issues. Modified from Annon JS. The Behavioral Treatment of Sexual Problems. Honolulu, Enabling System, 1974-1975.

1002

sexual concern (see Box 43-1). If the time constraints limit the current visit, the physician should offer the patient a future follow-up visit. Work together, to develop a treatment plan. In some cases, simply following the previous four steps may be therapeutic. Many clinical cases can be managed with brief education or limited advice, such as discussing normal physiologic sexual changes with aging or recommending books or products (e.g., water-based lubricant for vaginal dryness). When a referral has been made, scheduled follow-up supports the patient during the process and helps address administrative or adherence issues. Counseling may be extremely important, and the physician should research local resources. The American Association of Sex Educators, Counselors, and Therapists (AASECT) may be contacted for referral information (http://www.aasect.org).

Female Sexual Dysfunction Key Points • Low sex drive is the most common sexual problem reported by women. A woman distressed by her low sexual drive has hypoactive sexual drive disorder. • The cyclic model of sexual functioning postulates that arousal may be the initial trigger for a woman’s sexual encounter, not desire. • Ovarian androgens may play an important role in female sexual drive. Androgen levels in premenopausal women should be measured at the peak on days 8 to 10 of a 28-day menstrual cycle. • Women may believe they have primary inhibited orgasm disorder because, unlike many men, they do not reach orgasm solely with vaginal intercourse. • In most cases of orgasmic dysfunction, no specific physical examination or laboratory testing is necessary. • Vaginismus is an involuntary, usually painful, spastic contraction of the pelvic musculature surrounding the outer third of the vagina and is complete, partial, or situational.

The linear model of sexual functioning classifies female sexual dysfunction as disorders of sexual interest/desire, arousal, orgasm, or pain. The cross-sectional, populationbased PRESIDE study (Prevalence and Correlates of Female Sexual Disorders and Determinants of Treatment Seeking) estimated the prevalence of any female sexual problems was 44.2%, with “personal distress” reported by 22.8% of participants (Hatzichristou et al., 2004). Sexual dysfunction associated with personal distress became a disorder defined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSMIV-TR).

Hypoactive Sexual Desire Disorder For women, low sexual drive is the most frequently reported sexual problem. Four in 10 women state they have low sexual drive. The lack of sexual desire may not be distressing for all women, with “distress” prevalence ranging in studies from 23% to 61% (Lindau et al., 2007; Shifren et al., 2008). Hypoactive sexual desire disorder (HSDD) may be general (a general lack of sexual desire), situational (previously


resent sexual desire is now absent), acquired (beginning after p a period of normal sexual function), or lifelong (persistent no or low sexual desire). The cyclic model of sexual functioning postulates that arousal, not desire, may be the initial trigger for a woman’s sexual encounter. Recently, therefore, experts suggest defining HSDD as a recurrent, consistent lack of ability to experience any desire or arousal (Basson et al., 2004). A brief questionnaire can be helpful to screen patients for HSDD (see eTable 43-1 online). Female sexual desire is a complex interaction among biologic, psychological, social, interpersonal, and environmental components. Ovarian function, especially ovarian androgens, may play an important role. In women age 20 to 49, HSDD is almost threefold more likely in surgical postmenopausal women than premenopausal women. However, no significant difference in HSDD exists between naturally or surgical postmenopausal women over age 50 (Leiblum et al., 2006). Medical illnesses, such as thyroid disease, chronic pain conditions, urinary incontinence, and depression/anxiety, may negatively impact sexual desire. Medications can affect sexual drive, especially selective serotonin reuptake inhibitor (SSRI) antidepressants, antihypertensives, antipsychotics, and narcotics. Fear of pregnancy or sexually transmitted infection and discord or communication difficulty in a couple’s relationship may diminish sexual desire. The clinician must explore all aspects of the biopsychosocial model when evaluating a woman with hypoactive sexual desire. Evaluation for HSDD includes a thorough history and physical examination to detect any gynecologic, neurologic, cardiovascular, or endocrine disorders. Laboratory testing should include thyroid function, fasting glucose, lipid profile, and liver function. If a hormonal problem is suspected, prolactin, total and free testosterone, sex hormone–binding globulin (SHBG), dihydroepiandrosterone (DHEA), and estrogen levels may be drawn. Androgen levels in premenopausal women should be measured at the peak on days 8 to 10 of a 28-day menstrual cycle.

Treatment The U.S. Food and Drug Administration (FDA) has not approved any medication specifically for treatment of HSDD. Estrogen therapy improves vaginal dryness but does not affect sexual desire. The manufacturer of oral esterified estrogen and methyltestosterone discontinued distribution in the United States in March 2009. Although the transdermal testosterone patch is approved in Europe (Intrinsa), in 2004 the FDA did not approve it because of concerns regarding relatively low effectiveness, large placebo response, masculinizing side effects, and possible long-term consequences (cardiovascular and breast cancer when given with estrogen). Further Phase III clinical trials are ongoing. A randomized controlled trial (RCT) of sildenafil in postmenopausal women with SSRI-associated sexual dysfunction demonstrated a significant improvement in delayed orgasm and arousal (lubrication), but no improvement in desire (Nurnberg, 2008). In small studies, bupropion improves HSDD in premenopausal women and women taking SSRIs, but large-study data are lacking (Segraves et al., 2004). Given the lack of allopathic treatment for HSDD, many women turn to complementary and alternative therapies (CAM). DHEA, an

adrenocorticosteroid the body converts to testosterone, was found to improve sexual interest, thoughts, and fantasies in women with adrenal insufficiency, but studies are conflicting for women without adrenal insufficiency (Arlt et al., 1999). Limited data exist for Ginkgo biloba, damiana leaf, ginseng, and other proprietary herbal blends that are marketed to improve HSDD (Simon, 2009). For psychological interventions for HSDD, cognitive-behavioral therapy appears most beneficial (Basson et al., 2004).

Female Sexual Arousal Disorder The DSM-IV-TR defines female sexual arousal disorder as the inability to attain or maintain a genital lubrication-swelling response during sexual activity. The American Foundation for Urologic Disease recommended division of this diagnosis into subjective, genital, and combined subtypes. It also urged recognition of “persistent” sexual arousal disorder characterized by “spontaneous, intrusive, and unwanted genital arousal . . . unrelieved by one or more orgasms” (Basson et al., 2003). With the exception of persistent sexual arousal disorder, evaluation should include assessment for hypoactive sexual desire disorder. Neurologic and vascular causes should be considered when adequate genital vasocongestion and swelling do not occur but subjective arousal and lubrication are intact. Treatment is based on the suspected cause of the sexual arousal disorder. Supplemental water-soluble lubrication may be needed. Off-label use of PDE-5 inhibitors (e.g., sildenafil) may be helpful in restoring the vascular response (Kaplan et al., 1999). The FDA-approved Eros Clitoral Therapy Device uses a silicon cup to apply a vacuum to increase blood flow to the clitoris and surrounding tissue. The device appears effective in women without detectable disease and after radiation treatment for cervical cancer (Munarriz et al., 2003, Schroder et al., 2005), although sample sizes have been small. Herbal supplements and botanical genital massage oil showed some effect in small studies (Ito et al., 2001, Ferguson et al., 2003). Partner issues and situational factors may need to be addressed.

Female Orgasmic Disorder Orgasmic dysfunction, the inability to reach orgasm when desired, may be primary, with the patient never having experienced orgasm, or secondary, with the dysfunction manifesting after previous satisfactory orgasmic functioning. Some women may believe they have primary inhibited-orgasm disorder because, unlike many men, they do not reach orgasm solely with vaginal intercourse. Portrayals of female orgasm in novels and films are often overstated or misleading. A basic description of physical orgasm (i.e., pleasurable sensation in genital area and contractions of vagina, followed by a feeling of physical and psychological relaxation) may facilitate discussion of orgasm. Many women prefer simultaneous vaginal and clitoral stimulation, oral-genital sex, or clitoral stimulation alone to have an orgasm and do not have an orgasmic disorder. In both primary and secondary orgasmic dysfunction, it is important to ask about past or current experiences of violence, victimization. and abuse. Social factors also affect a woman’s experience of orgasm. Women taught negative messages regarding sexuality or with strict religious or cultural 1003

43


prohibitions on sexual attraction and thoughts may experience orgasmic difficulty, even if the specified conditions for sexual behavior (e.g., marriage) have been fulfilled. Women who were born later in the 20th century are more likely to experience orgasm than those born earlier, likely reflecting social changes. Secondary inhibited orgasm can be caused by other medical illnesses and contributing contextual factors. The clinical history in secondary inhibited orgasm should focus on the patient’s perception of this dysfunction: time and circumstances of onset, possible causes, effect on relationship(s), and treatment goals. Physiologic functioning during sexual stimulation, including adequacy of lubrication and ability to sustain states of high arousal, should be explored. Contributing factors such as fatigue, depression, postpartum physical and social changes, preoccupation with other life issues, substance abuse, and other medical illnesses should be considered. Contextual and relationship issues, including lack of tenderness or interest in non-intercourse stimulation by the partner, early ejaculation, problems regarding contraceptive responsibility, lack of privacy, relationship conflicts, and the possibility of abuse, should be discussed. In most cases of orgasmic dysfunction, no specific physical examination or laboratory testing is necessary. As with other sexual dysfunctions, neurologic, gynecologic, or other examination may be suggested by the clinical history. Treatment of orgasmic dysfunction usually involves increasing knowledge and sexual options for the patient and partner. Masturbation (self-pleasuring) may provide information about sexual responsiveness and preferred stimulations, which can then be transferred to sexual situations with the partner. Partner education regarding clitoral stimulation and adequate pre-intercourse lovemaking (foreplay) can change the focus from intercourse to mutual pleasuring, spontaneity, and sexual satisfaction. Referral for more in-depth therapy is indicated if the evaluation reveals significant relationship dysfunction, past abuse, or other severe medical or psychosocial complications.

Sexual Pain Disorders Vaginismus Vaginismus is an involuntary, usually painful, spastic contraction of the pelvic musculature surrounding the outer third of the vagina. It is classified as complete (e.g., precluding intercourse, tampon insertion, or other vaginal penetration), partial (resulting in dyspareunia or difficulty with other forms of vaginal penetration, including speculum examination), or situational (e.g., occurring when intercourse is anticipated). Vaginismus is often idiopathic. Many cases, however, may follow pelvic trauma, such as painful intercourse, sexual assault, rough gynecologic examination, complicated episiotomy, vaginal infections, pelvic inflammatory disease, or pelvic surgery. Childhood or adolescent sexual abuse may also lead to vaginismus during adulthood. Regardless of the cause of vaginismus (traumatic, psychological, or idiopathic), once a pattern of pain and anticipation of pain has been established, it will likely recur unless treatment is provided. Diagnosis is usually made by history. Patients report pain and difficulty with, or inability to engage in, vaginal intercourse or digital vaginal stimulation; using tampons or vaginal contraceptives; or having a pelvic examination. 1004

Patients may demonstrate visible contraction of the pelvic floor musculature with anticipated speculum examination. Physical examination may detect pertinent anatomic abnormalities, such as vaginal septa. Few studies exist on vaginismus. Uncontrolled reports suggest that sex therapy may be helpful (McGuire and Hawton, 2005). Vaginismus is not under the patient’s conscious control. Therapy must be directed at restoring conscious control under conditions that respect the patient’s autonomy and maintain the patient’s safety from further trauma. If the patient expresses fear or anxiety, pelvic examination may be deferred, and in severe cases, sedation may be necessary. Any physical abnormalities detected on pelvic examination, such as infections, should first be treated. After this, the patient may begin self-treatment with size-graded plastic or silicone vaginal dilators, gradually teaching her vagina to remain relaxed and receive nonpainful, self-controlled penetration (see Web Resources). Specialized physical therapists teach patients to use biofeedback to relax the pelvic floor musculature; this can be more effective than treatment with dilators and is often preferred by patients. Treatment of posttraumatic stress disorder and other sequelae of past trauma may be crucial. Referral to a sex therapist is often helpful.

KEY TREATMENT Cognitive-behavioral therapy appears beneficial for hypoactive sexual desire disorder (Basson et al., 2004) (SOR: B). Treatment of orgasmic dysfunction usually involves increasing knowledge and sexual options for the patient and partner (SOR: C). Sex therapy and vaginal dilators of increasing size may help treat vaginismus (SOR: C).

Dyspareunia Dyspareunia refers to pain experienced immediately before, during, or after intercourse. Diagnosis of dyspareunia is made by history and physical examination. Useful questions include the onset, duration, and circumstances in which this problem occurred, the location of the pain (e.g., superficial, deep, unilateral, bilateral), and whether it is specific to a particular partner or practice. Physical exam may reveal perineal trauma or vaginal infection, vaginal mucosal atrophy, or other anatomic factors (e.g., vaginal septa, partial vaginismus). Emotional factors may contribute, such as ambivalence or distaste regarding the sexual relationship, as well as the sequelae of childhood abuse. Inadequate lubrication, relationship difficulties, poor sexual technique or a rough or abusive partner can cause dyspareunia. Treatment of physiologic dyspareunia caused by atrophic vaginitis may require vaginal estrogen. Vaginal infections must be diagnosed and treated. For poor lubrication, supplemental water-based lubrication may be sufficient. Deep dyspareunia is often caused by overvigorous penetration or excess cervical pressure and may respond to brief educational interventions. Many people do not realize that penises and vaginas vary in length, and the vagina may not stretch to accommodate full penile engulfment. Changing position to allow the woman to control the amount of cervical pressure may ameliorate the dyspareunia. Referral for sex therapy for the couple may prove helpful. In some cases, the patient may be able to bring about change in the sexual relationship with


sufficient information and assertiveness. If dyspareunia is the result of deliberate carelessness or abuse by the partner, ending the relationship is usually the only reasonable option.

Male Sexual Dysfunction Key Points • The prevalence of erectile dysfunction increases with age. • Vascular risk factors (e.g. diabetes, smoking, sedentary lifestyle, and being overweight) increase the risk for ED. • Behavioral techniques for premature ejaculation are important for sustained success without pharmacologic treatment.

Erectile Dysfunction Historically, male sexual dysfunction was described as “impotence”; however, the term erectile dysfunction (ED) is now preferred. The National Institutes of Health (NIH) Consensus Development Conference (1992) defined ED as “the inability for a male to achieve an erect penis as part of the overall multifaceted process of male sexual function.” ED becomes “male erectile disorder” defined by the DSM-IV-TR when “marked distress or interpersonal difficulty” accompanies it, and is not better accounted for by another mental health disorder (other than a sexual dysfunction), and not exclusively caused by the direct physiologic effects of a substance (e.g., drug of abuse, medication) or a general medical condition. Both sympathetic and parasympathetic nerves regulate blood flow into the corpus cavernosum of the penis. Stimulation of the parasympathetic nerves causes release of nitric oxide (NO) from the noradrenergic, noncholinergic nerves and endothelial cells. NO increases the intracellular levels of cyclic guanosine monophosphate (cGMP) in the cavernosal smooth muscle, which relaxes the cavernosal tissues. With the resultant rapid blood flow into the corporal bodies of the penis, the small emissary veins that cross the tunica albuginea are occluded, and blood is trapped inside the corpus cavernosum, leading to an erection. The level of cGMP is also affected by prostaglandins. Phosphodiesterase-5 (PDE-5) is the main cGMP-catalyzing enzyme in human smooth muscle. PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) increase cGMP levels and facilitate and maintain penile erection. The intact functioning of four body systems— vascular, neurologic, endocrine, and usually psychological— is necessary for a man to experience a penile erection. Erectile dysfunction can occur at any age, but prevalence increases with age; 2% for ages 40 to 49, 6% for 50 to 59, 17% for 60 to 69, and 39% for 70 or older (Inman et al., 2009). Medical conditions associated with peripheral vascular disease, such as diabetes, coronary artery disease, stroke, and hypertension, increase the prevalence of ED. In men younger than 60, smoking, sedentary lifestyle, and being overweight increased the risk for ED (Bacon et al., 2003).

Evaluation Clinicians should carefully evaluate the patient’s complaint of ED, because some men consider premature ejaculation as “erectile dysfunction.” After obtaining the pertinent

istory, the clinician should carefully review the patient’s h past medical history. Because penile erection depends on intact vasculature, the medical history is similar to one assessing cardiovascular risk factors: “What is bad for the heart is bad for the penis.” Several common classes of medicines can cause sexual dysfunctions (Box 43-3). The social history should include the patient’s smoking, alcohol, and marijuana use, and the patient’s important social and sexual relationships. The physician should also assess psychological factors such as depression and anxiety. Physical examination focuses on signs related to the vascular, neurologic, and endocrine systems. Peripheral pulses should be palpated and carotids auscultated for bruits. The thyroid should be examined for enlargement or nodular disease. A thorough genitourinary examination should be performed. The clinician can assess perineal enervation with anal sphincter tone, perianal sensation, and the bulbocavernosus reflex. The penile shaft may show Peyronie’s disease (fibrous plaques of corpus cavernosa affecting erectile function or causing pain with erection). The prostate should be evaluated. Testicular atrophy may indicate low testosterone levels. If secondary sexual characteristics are lacking or the patient has other signs of hypogonadism, further endocrine evaluation should be undertaken. Few laboratory tests are necessary. Vascular risk factors should be assessed with fasting glucose and lipid profile. Blood urea nitrogen (BUN) and creatinine, serum transaminases (AST, ALT), thyroid-stimulating hormone (TSH), and prostate-specific antigen (PSA) levels should be considered. If the patient is young, is deficient in secondary sexual characteristics, or has other signs of hypogonadism, testosterone level should be determined. A low testosterone level, however, cannot be considered a definitive cause of ED. Many

Box 43-3 Medications Affecting Sexual Function Antihypertensives Beta blockers (atenolol, metoprolol, bisoprolol, propranolol) Thiazide diuretics (hydrochlorothiazide, chlorthalidone) Sympatholytics (clonidine, methyldopa) Calcium channel blockers (nifedipine, amlodipine) ACE inhibitors (enalapril, lisinopril) Antipsychotics Antidepressants (TCAs, SSRIs) Anxiolytics/tranquilizers Antiandrogens 5α-Reductase inhibitors Gonadotropin-releasing hormone agonists Ketoconazole Spironolactone H2blockers (cimetidine) HIV medications Fibrates (gemfibrozil, fenofibrate) Statins Digoxin Cytotoxic agents (methotrexate) ACE, Angiotensin-converting enzyme; TCAs, tricyclic antidepressants; SSRIs, selective serotonin reuptake inhibitors; HIV, human immunodeficiency virus.

1005

43


men with very low levels of circulating testosterone have normal libido and erectile function. Testosterone is highly protein-bound to SHGB, with only about 2% circulating as free testosterone; therefore, total testosterone levels may not reflect the bioavailable testosterone. The prevalence of abnormally low serum testosterone levels, even among men with ED, is only about 7%. Controversy surrounds testosterone supplementation for ED treatment.

Treatment Phosphodiesterase-5 inhibitors are first-line therapy for ED and are effective in most cases, including antidepressant-induced ED and diabetes related (Rudkin et al., 2004; Vardi and Nini, 2007). In 1998, sildenafil (Viagra) was the first PDE-5 inhibitor to become FDA approved, followed by vardenafil (Levitra) and tadalafil (Cialis) in 2003. The medications differ in absorption, potential effective time interval, and some side effects (Table 43-1). Evidence is insufficient to support one inhibitor over another (McVay, 2007). These medications have similar side effects, caused by their vasodilatory action. All PDE-5 inhibitors can cause increased vasodilation with nitrates and should not be used concomitantly; fatalities have been reported. Use with alpha-adrenergic blocker

medications should also be avoided due to risk of significant hypotension. Human immunodeficiency virus (HIV) protease inhibitors significantly increase the half-life of PDE-5 inhibitors by interfering with hepatic metabolism. PDE-5 medications have several dosages available to facilitate titration upward to an effective dose or dose reduction for age and hepatic or renal impairment. Prostaglandin E1 (PGE1; alprostadil) is second-line treatment for men who have a contraindication for or have failed PDE-5 inhibitors. Intraurethral alprostadil (MUSE— medicated urethral system for erection) is a pellet of synthetic PGE1 that is absorbed across the urethral mucosa and increases corpus cavernosum blood flow. Treatment has been effective in 50% of men with ED from radical prostectomy after sildenafil failed (Jaffe et al., 2004). Intracavernous selfinjection of alprostadil (Caverject, Edex) is another alternative, especially for patients with mild to moderate vascular disease not responsive to PDE-5 inhibitors. Complications, although relatively uncommon, include ecchymosis, hematoma, and painful erection. Although priapism occurs in less than 1% of users, patients should be warned to seek prompt medical attention if an erection lasts longer than 4 hours. Injection can also cause minor bleeding, so condom use is advised if blood-borne infection risk is present. Long-term

Table 43-1 Phosphodiesterase-5 (PDE5) Inhibitors

Parameter

Sildenafil (Viagra)

Vardenafil (Levitra)

Tadalafil (Cialis)

Dosages

25, 50, 100 mg

2.5, 5, 10, 20 mg

2.5 mg (taken daily), 5 mg, 10 mg (as needed dosing)

Absorption

Decreased if taken with high-fat foods

Decreased if taken with high-fat foods

Unchanged with food; decreased if taken with antacids

Onset of action

30-60 minutes

30-120 minutes

16-30 minutes

Length of effect

3-5 hours

4-5 hours

24-72 hours

Side effects

Headache, flushing, nasal congestion, dyspepsia, abnormal color vision

Headache, flushing, dyspepsia, nasal congestion, abnormal color vision

Headache, flushing, nasal congestion, dyspepsia; back pain, myalgia 12-24 hr after dose; color vision changes very rare

Metabolism

Hepatic

Hepatic

Hepatic

Drug interactions

Strong CYP3A4 inhibitors (e.g., ritonavir, indinavir, ketoconazole, itraconazole), moderate CYP3A4 (e.g., erythromycin), nonspecific

Strong CYP3A4 inhibitors (e.g., ritonavir, indinavir, ketoconazole, itraconazole) increase plasma levels; potential hypotension with nitrates and alpha-adrenergic blockers

Strong CYP3A4 inhibitors (e.g., ritonavir, indinavir, ketoconazole, itraconazole) increase plasma levels; potential hypotension with nitrates and alphaadrenergic blockers

Dose reduction

CYP450 inhibitor (cimetidine) causes significant increase in plasma levels; potential hypotension with nitrates and alpha-adrenergic blockers

Patients older than 65 years; hepatic impairment; no adjustment for moderate to severe renal impairment (CrCl 30 mL/min); not recommended for CrCl 200 CGG repeats

Turner’ syndrome

Sporadic

XO karyotype

XXY Males (Klinefelter’s syndrome)

Sporadic

XXY karyotype

Alzheimer’s disease

Multifactorial

APOE E4, multiple SNPs

Asthma

Multifactorial

Multiple SNPs

Coronary artery disease

Multifactorial

Multiple SNPs

Depression

Multifactorial

Multiple SNPs

Diabetes type 2

Multifactorial

Multiple SNPs

Diabetes, type I

Multifactorial

HLA variants and multiple SNPs

Venous thromboembolism

Multifactorial/autosomal dominant

Factor V Leiden FVL, proteins C and S, prothrombin G20210A, antithrombin III

Single-gene diseases

Chromosomal diseases

Multifactorial diseases

Data from Gene Tests (www.genetests.org); Online Mendelian Inheritance in Man (http://www.ncbi.nlm.nih.gov/omim/); and NHGRI GWAS catalog (http://www.genome.gov/26525384). *Most common mode of inheritance for each condition listed; for many common multifactorial conditions, there are rare instances of mutations in single genes causing a similar disease. SNPs, Single nucleotide polymorphisms.

s ingle-gene diseases when seeing patients, which can include causes of cancers, anemia, liver disease, developmental delay, and deep vein thrombosis. Making a correct genetic diagnosis can lead to lifesaving interventions for affected patients and their families. Much research is needed regarding the genetics of multifactorial disorders, and predispositional genetic testing for such conditions using newer markers (e.g., disease-associated SNPs) is not currently recommended. A few examples illustrate what can currently be done with genetics and genomics in primary care.

Hereditary Breast and Ovarian Cancer A family history of premenopausal breast cancer in a firstdegree relative doubles personal breast cancer risk. These women may benefit from earlier screening and should be counseled about the benefits of early detection. An autosomal dominant pattern of inheritance is seen in a much smaller number of families, perhaps 5% of women with breast cancer, known as hereditary breast and ovarian cancer (HBOC) syndrome. Current USPSTF guidelines suggest that physicians should recognize individuals from such families 1019

44

Clinical Genetics (Genomics)

because they may benefit from counseling about HBOC and testing for mutations in the BRCA1 and BRCA2 genes. The USPSTF recommends against using BRCA and mutation testing as a screening tool in the absence of a suggestive personal or family history. Numerous BRCA mutations have been found, and their prevalence in the general population is about 1 in 800, but up to 1 in 40 in people of Ashkenazi Jewish descent. Pretest and post-test counseling is very important for HBOC. The presence of many rare mutations and mutations of unknown clinical significance in the population can make interpretation of testing complicated, and involvement of a clinician with specialized knowledge is advisable. Women with BRCA mutations may have up to an 80% lifetime risk of breast cancer and a 40% risk of ovarian cancer depending on the mutation. The risk of other cancers is also greater, although less so. It is important to recognize that males with a BRCA mutation develop breast cancer at much higher rates than the general population. In fact, a diagnosis of male breast cancer should lead to a careful review of family history. Personal risk depends on the specific gene variant involved and other risk factors. Aggressive strategies aimed at early detection (e.g., breast MRI) are frequently recommended, but evidence of comparative effectiveness is lacking. Interventions such as bilateral mastectomy and oophorectomy have an enormous impact on women’s lives, but evidence suggests these surgeries may confer up to a 90% reduction in cancer risk (NCCN, 2008). Evidence regarding prophylaxis with tamoxifen or related agents is equivocal and may be related to the specific causal mutation. Although routinely offered to individuals with BRCA mutations, little evidence supports the use of annual CA-125 and transvaginal ultrasound to screen for ovarian cancer. Options for prevention and treatment are increasing over time, and more targeted and less invasive options may become available.

KEY TREATMENT Women with a family history suggestive of hereditary breast and ovarian cancer (HBOC) syndrome should be offered genetic counseling (USPSTF, 2005) (SOR: A). Enhanced breast cancer screening with annual mammograms and breast magnetic resonance imaging (MRI) starting at age 25, or 10 years earlier than the age of earliest diagnosis in the family, are recommended for individuals with BRCA mutations (NCCN, 2008; Saslow et al., 2007) (SOR: C). Prophylactic mastectomy and oophorectomy dramatically reduce the risk of breast and ovarian cancer in HBOC patients (NCCN, 2008) (SOR: B).

Hereditary Colorectal Cancer About 10% of the general population has a first-degree relative with colorectal cancer (CRC); this history increases personal lifetime risk for CRC to 9% to 16%. Many guidelines recommend early screening for these individuals—by age 40, or 10 years earlier than the age at diagnosis of a family member. Early detection and removal of adenomatous polyps have made determining family history more difficult. Patients should be asked about removal of polyps in relatives, and those who have adenomatous polyps should be encouraged to tell their families. 1020

A family history that contains many relatives with CRC, adenomatous polyps, or endometrial cancer, especially in more than one generation or with early-onset (age 3 mo Delayed: >6 mo

Major depressive disorder

Must have depressed mood or loss of interest or pleasure In addition to above, 5 of following 9 symptoms present for at least 2 weeks: depressed mood most of day, anhedonia, weight loss or gain, insomnia or hypersomnia, agitation or motor retardation, fatigue, feelings of worthlessness or excessive guilt, poor or decreased concentration, and recurrent thoughts of suicide or death Symptoms represent change from previous functioning Causes distress or social or occupational impairment

Onset common 6-12 mo after crisis or disaster Symptoms present for most of day, nearly every day, for 2 wk

Substance use or abuse

Numbing substances (e.g., alcohol, heroin, marijuana) and sedative-hypnotic abuse usually preferred

Most common 6-12 mo after crisis

Dissociative disorders

Dissociative amnesia, dissociative fugue, dissociative identity disorder (formerly multiple personality disorder), depersonalization disorder Disturbance consists of one or more episodes of inability to recall important personal information, usually of traumatic nature

Sequelae of enduring chronic trauma, abuse, or neglect

Generalized anxiety disorder

Persistent symptoms of excessive anxiety or worry for at least 6 mo Also associated with restlessness, being easily fatigued, poor concentration, irritability, and sleep disturbances Free-floating anxiety unrelated to specific person(s) or situation

Any time after trauma

Panic disorder (with or without agoraphobia)

Recurrent, unexpected panic attacks, defined as episodic periods of intense anxiety, often with physical symptoms (e.g., palpitations, tremors, chest discomfort) Symptoms develop abruptly, increase in intensity over 10 min Persistent concerns about having additional attacks Anxiety, worry about implications or consequences of attack (e.g., heart attack, losing control)


Specific phobia, social phobia (social anxiety disorder)

Specific phobias: excessive or unreasonable fear of specific objects or situations (e.g., animals, heights, needles), which provokes immediate anxiety response Patient avoids feared situation or object. Social phobias: fear of social or performance situations in which patient fears possible excessive scrutiny by others Patient constantly worried about acting in humiliating or embarrassing way.


Modified from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000. *DSM-IV-TR abridged criteria, 2000. †More than 4 weeks; see criteria for posttraumatic stress disorder (PTSD).

Continued

1028

Crisis Intervention, Trauma, and Intimate Partner Violence Table 45-1 Psychiatric Disorders Related to Trauma or Crisis—cont’d

Diagnosis

Diagnostic Criteria* and Symptom Picture

Onset/Duration

Brief psychosis

Presence of one or more: hallucinations, delusions, disorganized speech, and disorganized or catatonic behavior Eventual full return to premorbid level of functioning

At least 1 day to 65 years) the prevalence of all anxiety disorders appears to decline, except for GAD, which is maintained at 4% prevalence and may increase over time (Krasucki et al., 1998). GAD is often a recurring illness in which patients may experience periods of residual symptoms and occasional interepisode remissions (Angst et al., 2009). More than one third of patients with panic disorder have full remission with treatment, but about 20% have an unremitting and chronic course despite treatment (Katschnig and Amering, 1998). The onset of major depression can occur at any age, although the median age of onset is 30 (Kessler et al., 2005b). Depression is a highly recurrent illness, and each episode increases the likelihood of future episodes. Patients with a single episode have a 50% lifetime chance of recurrence, whereas those with three or more episodes have an almost 100% chance of recurrence without treatment (Eaton et al., 2008). Untreated depressive episodes can last 6 months or longer (Kessler et al., 2003).The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study found that a substantial number of patients receiving first-line treatment may require 8 weeks or more of treatment to achieve response or remission (Trivedi et al., 2006). Although most patients will recover from their depressive episode and return to normal functioning with treatment, approximately 15% of patients will continue to have an unremitting course, with worsening psychosocial functioning and higher risk for suicide (Eaton et al., 2008).

Neurobiology and Genetics The neurobiology of both depressive and anxiety disorders is complex and incompletely understood. In contrast to illnesses such as Parkinson’s or Huntington’s disease, no single area of brain pathology or anatomic lesion has been implicated in the development of anxiety or depression; rather, these illnesses appear to be mediated by dysregulation of complex interactions between neural circuits (Nestler et al., 2002). In depression, most lines of investigation have involved dysregulation of the hypothalamic-pituitary axis (HPA) and hippocampus, along with investigations of neural circuitry mediating mood, reward, sleep, appetite, motivation, and cognition. In particular, hyperactivity of the HPA axis in some depressed patients has been found to lead to hippocampal volume reduction, likely by reduction of brain-derived neurotrophic factor (BDNF) and changes in the mechanisms that mediate BDNF expression. However, whether reduced hippocampal volume is a partial cause or merely a result of depression is currently unclear, and it is not seen in all patients diagnosed with depression. Although epidemiologic studies show that depression appears highly heritable, with some studies showing that 40 to 50% of the risk may be genetic, no one gene appears implicated, and depression likely is the phenotypic expression of multiple genetic vulnerabilities, coupled with environmental stresses (physical/emotional trauma, viral illness), physical factors (e.g., preexisting or comorbid medical illnesses such as 1061

47

Anxiety and Depression

hypothyroidism or stroke), and random processes during brain development (Nestler et al., 2002). Neurobiologic research in anxiety disorders has focused on elucidating the neural networks involved in the fear response, but despite advances in neuroimaging, the exact mechanism of each anxiety disorder has yet to be completely understood. Strategies to understand the neuroanatomic underpinnings of panic disorder have focused on translational research, using conditioned fear in animals as a model for panic attacks in humans. Panic disorder patients may have an especially sensitive fear mechanism involving the central nucleus of the amygdala, the hippocampus, thalamus, hypothalamus, periaqueductal gray region, locus ceruleus, and other brainstem sites (Gorman et al., 2000). Other areas of focus in anxiety disorders have involved investigations into alterations of interoceptive processing of the anterior insula (Mathew et al., 2008). Both the insula and the anterior cingulate cortex (ACC) are thought to be the regions of the brain that form a representation of the visceral state of the body. A heightened sensitivity of this region may underlie the misinterpretation of bodily signals in panic disorder. Genetic epidemiologic studies have clearly documented that anxiety disorders aggregate in families and that this familial link primarily results from genetic factors (Smoller and Faraone, 2008). First-degree relatives of probands with the major anxiety disorders (panic disorder, social anxiety disorder, specific phobias, OCD) have a fourfold to sixfold increased risk of the index disorders compared to relatives of unaffected probands (Hettema et al., 2001). Genetic studies of GAD suggest that a common genetic susceptibility may apply to “clusters” of anxiety disorders and other comorbid disorders (Norrholm and Ressler, 2009). An overlap of genes may play a role in the development of multiple psychiatric conditions, including anxiety and depression.

Anxiety, Major Depression, and Medical Illnesses Key Points • A nxiety disorders and major depression often coexist. • The more severe the anxiety disorder, the greater is the likelihood of major depression. • Medical illnesses are associated with higher prevalence of anxiety and depression, and vice versa. • Medically ill patients with comorbid anxiety or depressive disorders adapt more poorly to physical symptoms, complicating disease management.

Interaction of Depression and Anxiety Major depression and anxiety are often found together, and each illness complicates the course and outcome of the other. Studies have consistently shown that anxiety disorders are the most frequently occurring comorbid disorder with major depression, with 50% to 60% of major depressed patients with both illnesses (Zimmerman et al., 2002). Anxiety can lead to depression in almost 60% of patients, whereas depression leads to anxiety in only 15% of patients (Mineka et al., 1998). Not surprisingly, the more severe anxiety 1062

isorders are more likely to lead to subsequent depression; d that is, panic disorder, agoraphobia, OCD, PTSD and GAD more frequently lead to depression compared to either social phobia or simple phobia. In addition, patients with both illnesses often have increased severity of symptoms, increased frequency of episodes (either mood or anxiety episodes), poorer response to treatment, higher suicide rates, a more chronic course, and overall poorer prognosis. Treatment is complicated by the fewer studies on coexisting depression and anxiety, providing clinicians with a smaller evidence-base for treatment decisions. Patients with comorbid major depressive disorders are half as likely subsequently to recover from panic disorder with agoraphobia or GAD, and comorbid major depression almost doubles the likelihood of recurrence of panic disorder with agoraphobia (Bruce et al., 2005). In addition, children and adolescents with anxiety disorders are at eight times the risk of additional depression (Angold et al., 1999). Practitioners must therefore be aggressive in screening for anxiety disorders in patients reporting depressive symptoms, as well as screening for depression in patients reporting anxiety symptoms.

Interaction of Depression, Anxiety, and Medical Illness A complex and reciprocal relationship exists between medical illnesses and comorbid anxiety and depressive disorders. Medical illnesses are associated with higher prevalence rates of anxiety and depression, and anxiety and depression are associated with higher rates of comorbid medical illnesses. Studies of patients with diabetes, cancer, stroke, myocardial infarction, HIV-related illness, and Parkinson’s disease have higher rates of depression compared to patients without such illnesses (Katon, 2003a). Common medical disorders seen in primary care settings have high comorbidity with anxiety disorders as well. Cardiovascular disease is associated with a 1.5 times greater risk of both GAD and panic disorder (Goodwin et al., 2008). Patients with back pain or arthritis are almost twice as likely to have panic attacks or GAD (McWilliams et al., 2004), whereas patients with asthma (pediatric or adult) may have a 30% increased likelihood of anxiety disorders (Katon et al., 2004). The prevalence of anxiety and depression in patients with diabetes is more than double that in the general population (Collins et al., 2009). Almost 100% of patients with irritable bowel syndrome will have major depression, GAD, or panic disorder (Lydiard et al., 1993). Medical illnesses are associated with a higher risk for mood and anxiety disorders, so the presence of these disorders places patients at higher risk for multiple medical conditions. Patients with GAD or panic disorder are almost six times more likely to have a cardiac disorder, three times more likely to have a gastrointestinal (GI) disorder, twice as likely to have respiratory difficulties, and twice as likely to have migraine headaches compared to patients without anxiety disorders (Harter et al., 2003). Depression may be a predictor for the subsequent development of medical illness. Several studies found an association between history of major depression and subsequent development of type II diabetes (Eaton et al., 1996; Kawakami et al., 1999) and coronary artery disease (Rugulies, 2002). Management of patients with comorbid medical illness and anxiety or depression is complex. Such patients have


higher rates of unexplained symptoms than patients without these disorders, even after adjusting for the severity of medical illness (Katon and Walker, 1998). An increasing body of literature suggests that patients with medical illness and comorbid depression/anxiety adapt more poorly to chronic symptoms, such as fatigue or pain, and tend to focus on both symptoms of their physical illnesses and physical symptoms associated with other organ symptoms. Not surprisingly, patients with medical illness and comorbid depression have 50% higher medical costs than patients with medical illness alone (Katon, 2003). Comorbid patients are more functionally impaired and have more lost workdays, poorer quality of life, and higher rates of medical utilization (Simon, 2003). Disease management is also complicated by higher rates of nonadherence to treatment and self-care regimens, as well as higher rates of risk behaviors (e.g., smoking, overeating, sedentary lifestyle). Response to antidepressant treatment may be less robust, as evidenced by patients with cardiovascular disease, stroke, and diabetes (Katon, 2003).

Diagnosis and Screening of Mood and Anxiety Disorders Key Points • D istinguishing unipolar from bipolar depression is critical for the proper management of depressed patients. The MDQ may aid practitioners in detecting bipolar disorder in primary care settings. • The PHQ-9 is a common and easy-to-use screening tool for depression. • No standard screening instrument for anxiety disorders has currently been accepted in general practice.

Diagnosis of Mood Disorders Mood disorders are divided into depressive disorders, bipolar disorders, and disorders based on etiology (i.e., mood disorders caused by general medical conditions and substanceinduced mood disorders). For primary care physicians, identification, treatment, and management of depressive disorders are essential. Bipolar disorders, which are typically more complex to identify and treat, are best referred to mental health professionals for ongoing treatment. Therefore, this chapter concentrates on identifying bipolar disorder and distinguishing between unipolar and bipolar depression, but does not delve into the specifics of treating bipolar patients. The essential feature of a major depressive episode is a period lasting at least 2 weeks during which the patient experiences depressed mood or loss of interest or pleasure in almost all activities, a distinct change in usual self, and clinically significant distress or changes in functioning. It is accompanied by a constellation of other symptoms, such as changes in sleep, eating, energy, motivation, and concentration; difficulty making decisions; and often feelings of hopelessness, worthlessness and guilt (Box 47-1). Patients may ruminate about death, feel that life is not worth living, have thoughts about suicide, may make plans to kill themselves, or make attempts. Many patients complain of memory difficulties, become easily distracted, and describe an inability to

Box 47-1 Diagnostic Criteria for Major Depressive Episode A. F ive (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations. 1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood. 2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others). 3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains. 4. Insomnia or hypersomnia nearly every day. 5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down). 6. Fatigue or loss of energy nearly every day. 7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely selfreproach or guilt about being sick). 8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others). 9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide. B. The symptoms do not meet criteria for a Mixed Episode. C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism). E. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.

think clearly. Patients often pace, wring their hands or have an inability to sit still; conversely, they may become greatly slowed or immobilized. In some patients, irritable mood may predominate more than sadness, or they may have explosive, angry outbursts (Fava and Rosenbaum, 1999). Irritability is especially noted in depressed children and adolescents. In its most severe forms—major depression with psychotic features—patients may hear voices telling them to kill themselves or may develop delusional beliefs, such as having a serious illness despite numerous tests providing no evidence (APA, 2000). The essential feature of dysthymia is a chronically depressed mood that occurs most days for at least 2 years. Patients may have a variety of other symptoms, such as feelings of inadequacy, generalized loss of interest or pleasure, social 1063

47


ithdrawal, feelings of guilt or brooding about the past, and w decreased activity, productivity, or effectiveness (Box 47-2). Neurovegetative symptoms such as insomnia or hypersomnia, poor appetite or overeating, low energy, and poor concentration may be present but are less common than in major depressive episodes. These patients may state that they have been depressed for as long as they can remember and cannot recall episodes of recovery or remission of symptoms. In addition, dysthymic patients may periodically have superimposed major depressive episodes, often called “double depression” (APA, 2000). Bipolar disorder is a chronic mood disorder characterized by the presence of mania (bipolar I disorder) or hypomania and depression (bipolar II disorder). Manic episodes are distinct periods of abnormally and persistent moods that can be euphoric, expansive, or irritable. Although manic patients are often thought to be always euphoric, only about 20% of patients experience pure euphoria; most describe a mix of severe irritability, severe emotional lability, and volatility (Goodwin and Jamison, 2007). Manic patients often have greatly inflated self-esteem, confidence, decreased need for sleep, pressured speech, racing or crowded thoughts, distractibility, increased involvement in goal-directed activities (e.g., starting many projects but being unable to finish any), hypersexuality, and excessive involvement in pleasurable activities with a high potential for painful consequences (APA, 2000). Patients can exert great levels of physical activity, appear tireless, and may become extremely physically agitated. Approximately 60% of bipolar I patients will experience psychosis, which may involve delusions of grandeur (feeling omnipotent, having special powers or “gifts”), persecution, or hallucinations (more often auditory as opposed to visual) (Goodwin and Jamison, 2007). Despite mania being the defining characteristic of the disease, depressed moods tend to predominate, with bipolar I patients experiencing a 3:1 ratio of depression to mania over the course of the illness (Judd et al., 2003). Primary care physicians are more likely to encounter patients with bipolar II disorder than bipolar I disorder. Bipolar II disorder is characterized by hypomanic and major depressive episodes, although over the course of the illness it is primarily a disease of depression, with depressive episodes predominating over hypomanic episodes by a 37:1 ratio (Judd et al., 2003). Symptoms of hypomanic episodes are similar to full manic episodes, but the severity of manic behaviors is attenuated, and the extreme functional, occupational, and social impairment evident in manic episodes is absent in hypomania. Current DSM-IV-TR criteria require that distinct elevations in mood must be present for at least 4 days, must be clearly different from the patient’s usual nondepressed mood, and must be accompanied by a change in the patient’s usual functioning. Because patients primarily seek help during their depressive episodes and typically do not report hypomanic episodes as abnormal, undiagnosed bipolar disorder remains a major difficulty in primary care settings (Manning et al., 1999). Moreover, bipolar disorder may be more common in primary care settings than in general populations. Of 649 patients being treated for depression in a primary care clinic, 21% screened positive for bipolar disorder (Hirschfeld et al., 2005), whereas 10% of patients screened positive for bipolar disorder in a general medical clinic, although 80% of these patients had been diagnosed with unipolar depression (Das et al., 2005). 1064

Box 47-2 Diagnostic Criteria for Dysthymic Disorder Depressed mood for most of the day, for more days than not, as indicated either by subjective account or observation by others, for at least 2 years. Note: In children and adolescents, mood can be irritable and duration must be at least 1 year. A. Presence, while depressed, of two (or more) of the following: 1. Poor appetite or overeating 2. Insomnia or hypersomnia 3. Low energy or fatigue 4. Low self-esteem 5. Poor concentration or difficulty making decisions 6. Feelings of hopelessness B. During the 2-year period (1 year for children or adolescents) of the disturbance, the person has never been without the symptoms in Criteria A and B for more than 2 months at a time. C. No Major Depressive Episode (see Criteria for Major Depressive Episode [Box 47-1]) has been present during the first 2 years of the disturbance (1 year for children and adolescents); i.e., the disturbance is not better accounted for by chronic Major Depressive Disorder, or Major Depressive Disorder, In Partial Remission. Note: There may have been a previous Major Depressive Episode provided there was a full remission (no significant signs or symptoms for 2 months) before development of the Dysthymic Disorder. In addition, after the initial 2 years (1 year in children or adolescents) of Dysthymic Disorder, there may be superimposed episodes of Major Depressive Disorder, in which case both diagnoses may be given when the criteria are met for a Major Depressive Episode. D. There has never been a Manic Episode, a Mixed Episode, or a Hypomanic Episode, and criteria have never been met for Cyclothymic Disorder. E. The disturbance does not occur exclusively during the course of a chronic Psychotic Disorder, such as Schizophrenia or Delusional Disorder. F. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism). G. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.

Unipolar Depression vs. Bipolar Depression Distinguishing unipolar from bipolar depression remains a critical distinction and poses one of the greatest clinical challenges for professionals who treat mood disorders. Misdiagnosis of bipolar disorder can lead to mistreatment (typically with antidepressants alone), worsening of mood, switches into mania or mixed states (i.e., presence of both manic and depressive symptoms), rapid mood swings, worsening psychosocial impairment, greater suicide attempts, and higher mortality (Goldberg and Ernst, 2002; Goldberg and Truman, 2003; Schneck et al., 2008). Treatment of bipolar depression is rarely straightforward and often requires multiple medications and medication trials. Antidepressants do not appear to be especially helpful in the treatment of bipolar disorder, and antidepressants have not yet been shown to improve outcome compared to mood stabilizers alone (Sachs et al., 2007). Although no symptom is pathognomonic for bipolar depression, certain features of depression may suggest that


a patient’s depression is a manifestation of bipolar illness. Bipolar depression can present similar to unipolar depression, but some depression features may help distinguish the two (Ghaemi et al., 2004; Perlis et al., 2006) (Table 47-1). If a primary care physician makes a diagnosis of bipolar disorder, the patient is best served by referral to a mental health provider, preferably with expertise in treating mood disorders.

Screening Tools for Depression Numerous screening measures have been specifically designed to detect depression, and many are sensitive to change over time when used repeatedly at follow-up visits. The integration of such tools into clinical practice, referred to as measurement-based care, may enhance care and improve clinical outcome. Measurement tools in the public domain and sensitive to change over time are most practical for primary care physicians because they are a cost-effective way to

Table 47-1 Features Suggesting Bipolar Depression

Feature

Bipolar

Unipolar

Substance abuse

Very high

Moderate

Family history

Almost uniform

Sometimes

Seasonality

Common

Occasional

First episode before age 25 years

Very common

Sometimes

Postpartum illness

Very common

Sometimes

Psychotic features before age 35

Highly predictive

Uncommon

Atypical features

Common

Occasional

Rapid on/off pattern

Typical

Unusual

Recurrent major depressive episodes (>3)

Common

Unusual

Antidepressant-induced mania/hypomania

Predictive

Uncommon

Brief episodes (3 months)

Antidepressant tolerance

Suggestive

Uncommon

Mixed depression (presence of hypomanic features within depressive episode)

Predictive

Rare

Tension, edginess, fearfulness

More common

Less common

Somatic symptoms (muscular, respiratory, genitourinary)

Less common

More common

Modified from Kaye NS. Is your depressed patient bipolar? J Am Board Fam Pract 2005;18:271-281; and Perlis RH, Brown E, Baker RW, Nierenberg AA. Clinical features of bipolar depression versus major depressive disorder in large multicenter trials. Am J Psychiatry 2006;163:225-231.

manage depressed patients over time (Trivedi et al., 2006). Self-report measures obviate the need for trained office personnel to administer tests. Depression screening measures do not diagnose depression but do provide critical information regarding symptom severity within a given period. Almost all measures have a statistically predetermined cutoff score at which depression symptoms are considered significant. When a depression screen is positive, an interview is necessary because screening will not include many confounding diagnostic variables (e.g., substance abuse, hypothyroidism, bereavement), and physician judgment is required. Screening measures do not address important clinical features of psychiatric illnesses (e.g., total duration of symptoms, degree of impairment) from other comorbid psychiatric conditions.

Patient Health Questionnaire 9 The Patient Health Questionnaire 9 (PHQ-9) is often used in primary care settings because of its ease of use, sensitivity to change over time, reliability, and validity (Kroenke et al., 2001). It uses only the nine depression items from the original self-report version of the PRIME-MD PHQ (Spitzer et al., 1999). Major depression is diagnosed if five or more of the depressive symptoms have been present at least “more than half the days” in the past 2 weeks, and if one of the symptoms is depressed mood or anhedonia. Other depressive syndromes (e.g., minor depression) are diagnosed if two, three, or four depressive symptoms have been present at least “more than half the days” in the past 2 weeks, and if one symptom is depressed mood or anhedonia. One of the nine test items (“thought that you would be better off dead or by hurting yourself in some way”) counts if present at all, regardless of duration. Using cutoff scores from 9 to 15, sensitivity ranges from 68% to 95%, with specificity from 84% to 95%. Using the cutoff score of 9, sensitivity is 95% and specificity 84%.

Quick Inventory of Depressive Symptomatology— Self Report (QIDS-SR) The 16-item Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16) is an instrument designed to screen for depression and to follow the changes in severity of depression over time (Rush et al., 2006). The QIDS-SR16 is a shortened version of the original 30-item Inventory of Depressive Symptomatology (IDS). The IDS includes criterion symptoms and symptoms typically associated with depression, such as anxiety and irritability, whereas QIDS assesses only the nine symptom domains used to characterize depressive episodes (sad mood, concentration, selfcriticism, suicidal ideation, interest, energy/fatigue, sleep disturbance, changes in appetite/weight, presence of psychomotor retardation or retardation). The total score on QIDS ranges from 0 to 27 (0-5,no severity; 6-10, mild; 11-15, moderate; 16-20, severe; 21-27, very severe). The QIDS was effective in assisting management of depression in the STAR*D study, the largest depression trial conducted thus far in the United States (Trivedi et al., 2006).

Screening for Bipolar Disorder Although no laboratory or imaging tests currently exist to distinguish unipolar depression from bipolar depression, screening questionnaires, as well as certain features of a 1065

47


patient’s history and symptomatology, may prove helpful. The Mood Disorder Questionnaire (MDQ) is a tool that combines DSM-IV criteria and clinical experience to screen for bipolar disorder in primary care settings (Hirschfeld et al., 2000). It is a brief, 1-page self-report questionnaire with 13 yes/no items and two additional questions regarding functioning and timing of mood symptoms, and typically can be completed in 5 minutes or less. Seven or more positive responses to questions about manic symptoms, plus positive responses to the severity of impairment (moderate or severe) and coincident timing of symptoms yields a positive screen. Specificity and sensitivity of the MDQ vary widely by clinical setting, having the best combination of the two when given to patients with suspected mood symptoms (93% specificity; 58% sensitivity) but performs more poorly in general community samples (97% specificity; 28% sensitivity) (Hirschfeld et al., 2003; Hirschfeld et al., 2005). Other screening tools for bipolar disorder do not offer the ease of use and higher reliability and validity of the MDQ.

Diagnosis of Anxiety Disorders The essential feature of generalized anxiety disorder is excessive anxiety and worry about a number of events or activities, occurring most days over 6 months. Patients have difficulty controlling the worry, report subjective distress, and may experience difficulties in social or occupational functioning. The intensity, duration, or frequency of the worry is out of proportion to the actual likelihood or impact of the feared event. Patients must have at least three associated physical symptoms, including restlessness, irritability, muscle tension, disturbed sleep, fatigability, and difficulty concentrating. The list of associated symptoms can be thought of as symptoms of inner tension (restlessness or edginess, irritability, muscle tension) and symptoms associated with the fatiguing effects of chronic anxiety (fatigue, concentration difficulties, sleep disturbance) (Box 47-3). Panic attacks, a collection of distressing physical, cognitive, and emotional symptoms, may occur in a variety of anxiety disorders, such as specific phobias, social phobias, PTSD, and acute stress disorder. Panic attacks are discrete periods of intense fear in the absence of real danger, accompanied by at least 4 of 13 cognitive and physical symptoms (Box 47-4). The attacks have a sudden onset, build to a peak quickly, and are often accompanied by feelings of doom, imminent danger, and a need to escape. Symptoms of panic attacks can include somatic complaints (e.g., sweating, chills), cardiovascular symptoms (pounding heart, accelerated heart rate, chest pain), neurologic symptoms (trembling, unsteadiness, lightheadedness, paresthesias), GI symptoms (choking sensations, nausea), and pulmonary symptoms (shortness of breath). In addition, patients with panic attacks may worry they are dying, “going crazy,” or have the sensation of being detached from reality. Patients with panic disorder experience recurrent, unexpected panic attacks, followed by at least 1 month of persistent worry that they will suffer another panic attack. Panic disorder patients may begin to avoid places where a prior attack occurred or where help may not be available; such avoidance can lead to the development of agoraphobia and typically worsens their psychosocial functioning (Box 47-5). 1066

Screening Tools for Anxiety Disorders At present, screening tools for anxiety disorders have been developed to recognize anxiety as a broad syndrome, examining somatic symptoms (racing heart, lightheadedness) or cognitive symptoms (tendency to worry, intensity of worry). Other tools have been used to screen for single, distinct disorders, such as phobias or panic disorder. To date, no clear screening tool or symptom-severity measure has emerged for use in primary care settings, although newer instruments may be useful for primary care physicians. The Generalized Anxiety Disorder 7 (GAD-7) scale was developed and validated Box 47-3 Diagnostic Criteria for Generalized Anxiety Disorder Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities. A. The person finds it difficult to control the worry. B. The anxiety and worry are associated with three (or more) of the following six symptoms: 1. Restlessness and feeling keyed up or on edge 2. Being easily fatigued 3. Difficulty concentrating or mind going blank 4. Irritability 5. Muscle tension 6. Sleep disturbance C. The focus of the anxiety and worry is not confined to features of an Axis I disorder, e.g., the anxiety or worry is not about having a Panic Attack. D. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. E. The disturbance is not due to the direct physiological effects of a substance or a general medical condition. From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.

Box 47-4 Diagnostic Criteria for Panic Attack A discrete period of intense fear or discomfort, in which four (or more) of the following symptoms developed abruptly and reached a peak within 10 minutes: 1. Palpitations, pounding heart, or accelerated heart rate 2. Sweating 3. Trembling or shaking 4. Sensations of shortness of breath or smothering 5. Feeling of choking 6. Chest pain or discomfort 7. Nausea or abdominal distress 8. Feeling dizzy, unsteady, lightheaded, or faint 9. Derealization (feelings of unreality) or depersonalization (being detached from oneself) 10. Fear of losing control or going crazy 11. Fear of dying 12. Paresthesias (numbness or tingling sensations) 13. Chills or hot flushes From the American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.


Box 47-5 Diagnostic Criteria for Panic Disorder without Agoraphobia A. Both (1) and (2): 1. Recurrent and unexpected panic attacks 2. At least one of the attacks has been followed by 1 month (or more) of one (or more) of the following: (a) Persistent concern having additional attacks (b) Worry about the implications of the attack or its consequences (e.g., losing control, having a heart attack, “going crazy”) (c) A significant change in behavior related to the attacks B. Absence of Agoraphobia. C. The Panic Attacks are not due to the direct physiological effects of a substance or a general medical condition. D. The Panic Attacks are not better accounted for by another mental disorder. From the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.

in primary care clinics and is a brief, seven-item self-report screening tool for GAD (Spitzer et al., 2006). The GAD-7 helps identify probable cases of GAD and measure symptom severity. A score of 10 or greater represents a reasonable cutoff point for identifying patients with GAD, and cutoffs of 5, 10, and 15 correlate to mild, moderate, and severe levels of anxiety. An extended version of the PHQ includes five questions for panic disorder (Spitzer et al., 1999), but its utility as a stand-alone tool is currently unclear. The Overall Anxiety Severity and Impairment Scale (OASIS) is a five-item continuous measure that can be used across anxiety disorders, with multiple anxiety disorders, and with subthreshold anxiety symptoms. OASIS can be used to measure the severity of anxiety symptoms, but it was not developed as a diagnostic tool for any specific disorder (Norman et al., 2006).

Assessment of the Depressed or Anxious Patient in Medical Settings Key Points • P atients with anxiety and depressive disorders often present with somatic complaints. • Risk assessment includes identifying modifiable risk factors and developing a corresponding treatment plan. • “Contracts for safety” have no empiric data to support their effectiveness in risk management. • Worsening symptoms or suicidal ideation may require psychiatric hospitalization.

Diagnosing anxiety and depressive disorders may prove especially challenging in medical settings. The majority of patients suffering from such illnesses will more frequently present with somatic complaints, while only a minority will present with purely psychological symptoms and concerns (Bridges and Goldberg, 1985). Difficulties in diagnosis may be secondary to a patient’s inability to articulate psychological problems, reticence to speak of emotional difficulties, the

short time allowed for patient visits, or a primary care physician’s relative lack of training in assessing and treating mental health disorders. Many presenting complaints may be consistent with symptoms of coexisting medical illnesses, further complicating assessment and likely requiring additional etiologic investigation. Of new patients presenting to an urban clinic, for example, only 17% presented with purely psychological symptoms. Of the remaining patients, 32% presented with pure somatization, 27% presented with symptoms for a coexisting medical illness, and 24% presented with an initial physical complaint that they were later able to relate to a psychological problem (Bridges and Goldberg, 1985). However, clinical clues in patients with physical complaints may identify a subgroup of patients who warrant further evaluation for an anxiety or depressive disorder. This includes patients who present with multiple physical symptoms (six or more), have higher ratings of symptom severity and lower ratings of overall health, and have an encounter that the physician perceives as “difficult” (Kroenke et al., 1997). Assessment of anxious or depressed patients requires establishing specific psychiatric diagnosis(es), providing a thorough risk assessment (i.e., suicidality, homicidality, ability or inability to care for self), assessing the severity of the illness, identifying specific target symptoms to track over time, assessing factors that are likely complicating or exacerbating the illness (e.g. medical disorders, substance abuse), and gathering collateral information whenever possible from family, friends, or other providers (Box 47-6). Distinguishing bipolar from unipolar depression, as discussed previously, is one of the most important distinctions when establishing diagnosis. In addition, clinicians should look for the presence of comorbid anxiety disorders, because patients with such disorders often require lower initial antidepressant dosing and may have their anxiety symptoms paradoxically worsen as treatment is initiated unless lower doses are used (Table 47-2). Education on the medical nature of depression and anxiety may prove extremely helpful, because both patients and families often believe that psychiatric illness is evidence of “weakness” or indicative of some other personal failing. Information on prognosis and the expected treatment course may lessen pressure and expectations for rapid improvement and let the patient know when to expect medication benefit. Physicians should assess the severity of illness and develop a list of target symptoms to track and measure over time, to better evaluate treatment response. Tracking specific symptoms particular to an individual patient’s depression improves objective assessment of change. Often, patients’ neurovegetative symptoms will improve before the subjective experience of their mood improving. Assessing sleep, appetite, energy level, anxiety, and concentration allows the physician to select a more appropriate antidepressant or anxiolytic by targeting specific symptoms. This may include using a sedating antidepressant such as mirtazapine for patients with insomnia or a more activating antidepressant such as bupropion for patients with lethargy or somnolence. Measurement tools that are symptom specific and sensitive to change over time (e.g., PHQ-9, QIDS-SR) may help the physician track such changes. In addition, assessing overall functionality (ability to shower, pay bills, shop, prepare meals) is equally important in establishing the degree of impairment caused by the patient’s mood disorder. 1067

47


Box 47-6 Initial Assessment of Anxious or Depressed Patients 1. E stablish diagnosis. 2. Perform risk assessment. Suicide risk Risks to others 3. Establish severity of illness. Ability to care for self Functioning/functional impairment 4. Identify specific target symptoms. Neurovegetative symptoms (e.g., sleep, appetite, concentration) Use of measurement scales (e.g., QIDS) 5. Assess factors complicating illness. Alcohol or /drug use Comorbid or contributing medical conditions 6. Gather input from family and friends if possible.

Table 47-2 Dosing for Common Antidepressant and Antianxiety Agents

Usual Daily Starting Dose (mg) Medication

Anxiety

Depression

Daily Dose Range

Selective Serotonin Reuptake Inhibitors (SSRIs) Citalopram

10

20

10-60

Escitalopram

5

10

5-30

Fluoxetine

10

20

20-80

Fluvoxamine

25

50

100-300

Paroxetine

10

20

20-60

Sertraline

25

50

50-200

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Desvenlafaxine

50

50

50-100

Duloxetine

30

30

30-120

Venlafaxine

37.5

75

150-300

Tricyclic Antidepressants (TCAs) Amitriptyline

25

50

100-300

Imipramine

25

50

100-300

Nortriptyline

10

25

50-200

Desipramine

25

50

100-300

Norepinephrine-Dopamine Reuptake Inhibitors Bupropion

—

150

300-450

Norepinephrine-Serotonin Modulators Mirtazapine

1068

15

30

30-60

Differential Diagnosis Many medical conditions may cause or mimic depression. Physical disorders that have been associated with depression include Addison’s disease, acquired immunodeficiency syndrome (AIDS), coronary artery disease (especially in those with myocardial infarction), cancer, multiple sclerosis, Parkinson’s disease, anemia, diabetes, acute infection, temporal arteritis, hypothyroidism, and especially dementias. It is imperative that the physician complete a neurologic evaluation to rule out an underlying disorder as the cause of the patient’s depression. In addition, many medications may worsen depression, especially cardiovascular drugs, hormones, typical antipsychotic agents, anti-inflammatory agents, and anticonvulsants. Anxiety disorders may be caused or exacerbated by medical conditions, medications taken for other psychiatric or medical disorders, and other substances with stimulant properties. For example, hyperthyroidism can mimic or exacerbate anxiety disorders, and therefore thyroid function should be carefully evaluated when patients present with anxiety symptoms. In addition, lifetime risk of thyroid dysfunction appears higher in patients with panic disorder or GAD (Simon et al., 2002). Physicians should also assess the patient’s use of other medications, especially stimulants (whether prescribed or obtained from other sources), nicotine, illicit drugs, and caffeine.

Suicide Screening and Assessment Identifying patients at risk for suicide is a complex and difficult task, particularly in the setting of a busy medical practice. Suicide is currently the 11th leading cause of death for all ages and accounts for approximately 32,000 deaths annually in the United States (CDC, 2009). It is the second leading cause of death in those 25 to 34 years old and the third leading cause in those 15 to 24. Older males 75 and older have the highest suicide rate, at 37.4 per 100,000. Males continue to take their lives at approximately four times the rate of females and account for almost 80% of all U.S. suicides. Women in their 40s and 50s have the highest rates of suicide among females (8 per 100,000), and women continue to make suicide attempts two to three times more often than men (Krug et al., 2002). Approximately 60% of all suicides are associated with patients with mood disorders, and approximately 50% of patients who completed suicide had contact with professional help in the month before their death (Isometsa et al., 1995). Despite no definitive suicide assessment tool being available, risk factors have been defined that can help identify patients at risk for suicide. Suicide screening should include assessing current level of depression, severity of symptoms, feelings of hopelessness; current suicidal thoughts and behaviors (as well as past attempts), use of drugs or alcohol (which can increase levels of impulsivity and worsen dysphoria), current levels of anxiety and agitation, access to lethal means (especially firearms), presence of psychosis (command hallucinations, poor reality testing), recent acute stressors, and presence (or absence) of a psychosocial support system (APA, 2003). When possible, additional information from family or friends can be helpful in assessing statements or behaviors that may indicate a patient’s intentions of committing suicide.


Physicians should be alert to those suicide risk factors that can be modified. Although numerous historical and biologic risk factors cannot be modified (history of suicide attempts, family history of suicide, male gender, history of childhood trauma), other risk factors are amenable to intervention. Mood, anxiety, and psychotic symptoms can be successfully treated with medications. Substance abuse referral may help the patient actively struggling with substance abuse or dependence, or for relapse prevention. Encouraging the patient to mobilize psychosocial resources, such as contacting family members for support, can provide a measure of safety while the patient is recovering from depression. Removing access to firearms can be especially helpful in preventing rapid access to lethal means during episodes of acute distress and high levels of impulsivity. Physicians should be aware that “contracts for safety” have not been shown to be effective in preventing suicide and may provide a false sense of patient safety (Rudd et al., 2006). Continued assessment of mood, hopelessness, and suicidal ideation is required throughout the course of treatment. Worsening symptoms, along with plans or active preparations for suicide, may require increased observation or hospitalization.

Management and Treatment of Major Depression and Anxiety Disorders The key objective in treating depressive and anxiety disorders is remission of all symptoms. Studies in the treatment of major depression have consistently shown that lack of remission is associated with higher relapse rates, more severe subsequent depressions, shorter duration between episodes, continued impairment in work settings and social relationships, increased all-cause mortality, and increased risk of suicide (Judd et al., 2000). Initiation of treatment should include education about the expected temporal course of improvement; importance of regular eating, activity, social interaction, and sleep; medication selection; follow-up schedule; and safety management if symptoms worsen or suicidal ideation is evident (Box 47-7).

Box 47-7 Initiation of Treatment for Major Depression and Anxiety Disorders 1. E ducate the patient. Details of illness Treatment course, prognosis, goal of treatment (remission of symptoms) Importance of general health: exercise, sleep hygiene, nutrition Inclusion of family when possible Coordination with other providers Resource lists for support groups, therapy referrals 2. Select medication from reasonable choices. Patient history of antidepressant use/response Family history of antidepressant response Typical time course to antidepressant response 3. Administer starting dose, and initiate dose titration. Common side effects of medications 4. Establish monitoring with measurement-based care (e.g., QIDS). 5. Schedule follow-up in 2 to 4 weeks.

Depression Pharmacotherapy remains the mainstay treatment of depression. Treatment should be considered for the majority of depressed patients, especially those who are suicidal, functionally impaired from their depression, or experiencing a recurrent episode, or who have comorbid medical or psychiatric conditions likely to worsen unless their depression is treated (e.g., panic, GAD, chronic pain). Treatment of depression has clearly been shown to prevent relapse, shorten current episodes, decrease psychosocial impairment, decrease risk of suicide, and improve quality of life. Mild depression may be treated with symptomatic intervention alone (e.g., mild sedative for insomnia), although continuing depressive symptoms or inadequate response to purely symptomatic interventions warrants more aggressive treatment of the underlying depression. Patients with psychotic depression typically require treatment with both antidepressant and antipsychotic agents, or they may require electroconvulsive therapy (ECT). Often, psychotically depressed patients require hospitalization. Patients with psychotic depression should be referred to a psychiatrist, given the severity of illness and complexity of treatment. Again, the aim of treatment is remission of all depressive symptoms and a return to the patient’s previous baseline functioning. Pharmacotherapy combined with psychotherapy has been shown to be superior to either modality alone (de Maat et al., 2008; Thase, 1997); thus referral to a psychotherapist may be helpful, especially for patients with moderate to severe depression. Some patients may choose psychotherapy alone to treat depression; cognitive- behavioral therapy, interpersonal therapy, behavioral activation, and psychodynamic therapy may prove as effective as medication alone.

Selection of Medication The effectiveness of antidepressants is generally comparable across classes, and therefore selection of an antidepressant depends mainly on patient preference, side effect profile, drug interactions, previous response to a specific medication, treatment overlap with other psychiatric conditions, and cost (Tables 47-3 and 47-4). Minimal data support the increased efficacy or speed of onset for any particular agent, with response rates across clinical trials generally 50% to 75% for patients receiving active treatment. Onset of improvement typically takes 3 to 6 weeks, although the STAR*D study indicates that patients may require up to 12 to 14 weeks to achieve remission of symptoms. In fact, 40% of patients in the multiyear, multisite STAR*D study who eventually achieved remission in the first level of treatment with citalopram did not show a response (i.e., 50% improvement in symptoms) until week 8 of treatment (Trivedi et al., 2006). For most patients, initial treatment with a selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), bupropion, or mirtazapine is reasonable. Tricyclic antidepressants (TCAs) are more often used as second-line agents in the treatment of depression because of their potential toxicity in overdose, greater side effect burden (largely from anticholinergic, antihistaminic, and antiadrenergic properties), and potential cardiac complications (conduction delays). Monoamine oxidase 1069

47


inhibitors (MAOIs) are complex drugs to use given their potentially fatal drug and dietary interactions and probably should not be prescribed in family practice settings. Most antidepressant studies have been conducted in specialty settings, but a number of studies in primary care settings have also shown the superiority of antidepressants over placebo (Arroll et al., 2009). Thus, given the comparable speed and efficacy of antidepressants across classes and within classes, selection of an antidepressant agent may be primarily guided by side effect profile, possible secondary uses of antidepressants (e.g., treating pain or insomnia), and contraindications to particular agents (e.g., bupropion in seizure disorder patients). Table 47-2 gives the usual starting doses for treatment of major depression. Serotonin reuptake inhibitors are safe, effective medications that can treat a variety of psychiatric conditions. All SSRIs operate by the same mechanism of action and are considered equally effective in the treatment of depression. However, failure of one SSRI does not necessarily imply failure of all SSRIs; patients may respond preferentially to one SSRI over another (Rush et al., 2006). SSRIs differ substantially by their potential to inhibit particular hepatic cytochrome P-450 metabolic pathways, by half-life, potency, and presence or absence of active metabolites. Clinicians should

check for drug interactions in patients receiving complex polypharmacy regimens, because drug-drug interactions are constantly being updated and changing. For example, fluoxetine is a potent 2D6 inhibitor that can triple TCA and phenytoin levels or increase the anticoagulation associated with warfarin. Fluoxetine also has the longest half-life of any SSRI; its active metabolite norfluoxetine has a half-life of 10 days. SSRIs have sexual side effects (decreased libido, delayed orgasm or anorgasmia) and GI side effects (nausea, diarrhea) (see Table 47-4). GI side effects likely will remit over time, but sexual effects typically do not attenuate and may require treatment with other agents, such as a phosphodiesterase inhibitor (e.g., sildenafil), or choosing an antidepressant less likely to cause sexual side effects. Serotonin-norepinephrine reuptake inhibitors (venlafaxine, duloxetine, desvenlafaxine) are similar in efficacy to SSRIs, although a few studies have suggested a mild advantage of SNRIs over SSRIs (Thase et al., 2001). Although SNRIs by definition inhibit the reuptake of both serotonin and norepinephrine, dual-neurotransmitter reuptake inhibition does not occur with venlafaxine until doses reach approximately 150 mg daily; below this dose, it acts primarily as an SSRI. Venlafaxine is available in immediate-release and extended-release (XR) formulations, although most patients

Table 47-3 FDA Indications for Antidepressant Therapy

MDD

Amitriptyline

X

Migraine prophylaxis, chronic pain

Bupropion

X

Smoking cessation

Citalopram

X

Desvenlafaxine

X

Desipramine

X

Duloxetine

X

X

Escitalopram

X

X

Fluoxetine

X

Fluvoxamine

OCD

X

Panic

PTSD

GAD

Soc Anx

PMDD

Bulimia

Other/OffLabel Uses

Medication

Diabetic peripheral neuropathic pain, fibromyalgia

X

X

X

X/Pediatric depression

X

Imipramine

X

Enuresis

Mirtazapine

X

Nortriptyline

X

Paroxetine

X

X

X

Sertraline

X

X

X

Venlafaxine

X

X

X X

X

X X

Premature ejaculation

X

FDA, U.S. Food and Drug Administration; MDD, major depressive disorder; OCD, obsessive-compulsive disorder; PTSD, posttraumatic stress disorder; GAD, generalized anxiety disorder; Soc Anx, social anxiety disorder; PMDD, .

1070


Table 47-4 Common Side Effects of Antidepressant Medications

Class/Drug

Side Effects

Comments

Selective serotonin reuptake inhibitor (SSRI)

Gastrointestinal side effects (nausea, diarrhea, heartburn); sexual dysfunction (decreased libido, delayed orgasm): headache; insomnia/ somnolence

Likely little difference between SSRIs in rates of sexual side effects. SSRIs have been used to treat premature ejaculation.

Serotoninnorepinephrine reuptake inhibitor (SNRI)

Hypertension, sweating, nausea, constipation, dizziness, sexual dysfunction

Risk of increased blood pressure escalates as dose is increased; abrupt withdrawal of venlafaxine may cause discontinuation syndrome.

Tricyclic antidepressant (TCA)

Dry mouth, constipation, blurry vision, orthostatic hypotension, weight gain, somnolence, headache, sweating, sexual dysfunction

Use with caution in patients with cardiac conduction delays.

Bupropion

Insomnia, dry mouth, tremor, headache, nausea, constipation, dizziness

Contraindicated in patients with seizure disorders or eating disorders; patients generally free of sexual side effects.

Mirtazapine

Somnolence, increased appetite, and weight gain, dry mouth

Sedation may be more pronounced at lower doses.

Trazodone

Sedation, orthostatic hypotension, priapism

Usually used as a sedative-hypnotic.

Benzodiazepines

Sedation, fatigue, ataxia, slurred speech, memory impairment, weakness

Risk of dependence or abuse, especially with shorter-acting benzodiazepines.

and clinicians favor use of the XR preparation, given its oncedaily dosing and lower likelihood of provoking a withdrawal syndrome on discontinuation of the drug, more frequently observed with the immediate-release formulation. Desvenlafaxine, the active metabolite of venlafaxine, is more potent than its parent compound, but any advantages over venlafaxine are currently unclear. Unlike venlafaxine, duloxetine provides dual-neurotransmitter reuptake inhibition at any dose, although this does not appear to confer any advantage over other SNRIs in terms of efficacy or side effect profile. Duloxetine currently is indicated for treatment of chronic pain as well as depression, but this is likely a class effect of SNRIs and not unique to duloxetine. Side effects are similar to SSRIs (see Table 47-4), with the additional side effects with SNRIs likely caused by increased noradrenergic activity,

including dose-related hypertension, excessive sweating, and dry mouth (Thase, 2008a; Thase et al., 2005). Mirtazapine is a serotonin-norepinephrine modulator that also blocks postsynaptic hydroxytryptamine (HT) receptors, including those in the 5-HT-3 (serotonin) class. Mirtazapine is sedating and can increase appetite and therefore may be favored when patients have insomnia or decreased appetite and weight loss. Because of a dose-dependent ratio of neurotransmitter blockade involving histamine receptors, mirtazapine is generally more sedating at lower doses than higher. Although currently indicated only for depression, mirtazapine is reported to have general anxiolytic effects and may be beneficial for patients with mild to moderate anxiety. With its 5-HT-3 blockade, mirtazapine may be helpful when patients complain of nausea or other GI symptoms or side effects from SSRIs. Mirtazapine also has fewer sexual side effects than SSRIs or SNRIs, and has been tried as an antidote to SSRI-induced sexual side effects. Common side effects from mirtazapine include weight gain and daytime somnolence (see Table 47-4). Bupropion is pharmacologically unique among antidepressants and is manufactured in immediate-release, slow-release (SR), and XR formulations. Although its primary mechanism of action is unclear, the drug has weak norepinephrine and dopamine reuptake inhibition. Bupropion is an activating drug, making it better suited for patients with poor energy or who feel they cannot tolerate a sedating medication. It is also virtually free from sexual side effects and has been used with limited success as an antidote for patients with SSRIinduced sexual side effects (Clayton et al., 2004). Bupropion rarely causes weight gain and is therefore a good choice for patients who are obese or who feel they cannot tolerate weight gain. Unlike SSRIs, SNRIs and TCAs, bupropion does not treat anxiety disorders and may even worsen anxiety in patients because of its activating properties. Bupropion carries a black-box warning against its use in patients with a history of seizures or eating disorders; the latter group was shown to have a higher incidence of seizures in clinical trials. Given its greater propensity for seizures, bupropion dosing should not be pushed above the FDA-recommended dosing limits. Bupropion has also been approved for treatment of smoking cessation and therefore may have particular utility for depressed patients who also want to quit smoking. Tricyclic antidepressants are effective medications for treating depression and anxiety, with evidence of being more effective than SSRIs for severe depression, but TCAs confer a greater side effect burden than newer antidepressants and can be fatal in overdose. TCAs are divided into tertiary and secondary amines. Tertiary amines, such as amitriptyline and imipramine, have greater anticholinergic, antihistaminic and α-adrenergic blockade side effects than secondary amines, such as their respective metabolites nortriptyline and desipramine. TCAs offer an advantage over other antidepressants in that blood levels can readily be checked and dosing individualized. Reasonable evidence suggests TCAs may be more effective in severely depressed patients (Agency for Health Care Policy Research, 1999). In addition, nortriptyline has a therapeutic window, with superior antidepressant efficacy if levels are maintained at 50 to 150 ng/mL. Because of cardiac conduction side effects, however, TCAs must be used with caution in patients with conduction delays or who are taking class I antiarrhythmic agents, and electrocardiograms 1071

47


(ECGs) should be checked and monitored in patients older than 50 or those with suspected cardiac disease. TCAs also may cause tachycardia and orthostatic hypotension and thus should be used with caution in patients at risk for tachyarrhythmias or falls. The greatest single disadvantage to TCAs is their potential lethality in overdose; a typical 10-day supply can be lethal, and therefore TCAs should be prescribed cautiously in patients at high risk for suicide. TCAs are also used in a variety of headache and pain syndromes and thus may be useful in patients with such comorbidities. Trazodone is structurally distinct from SSRIs, TCAs, tetracyclics or MAOIs, but it still inhibits neuronal uptake of serotonin. Although the U.S. Food and Drug Administration (FDA) has approved it as an antidepressant, trazodone is most often used as a sedative-hypnotic. Dosing as an antidepressant is usually 300 to 450 mg, whereas sedative-hypnotic dosing is usually 50 to 150 mg. Risks and side effects of trazodone include sedation, priapism, and myocardial irritability; the latter effect includes the potential of inducing torsades de pointes.

Box 47-8 Assessing Antidepressant Treatment 1. 2. 3. 4. 5. 6. 7. 8. 9.

onitor effectiveness of treatment. M Continue assessment of specific symptoms. Assess need for further titration of medication. Continue to use measurement-based care. Assess any worsening of mood, increased irritability, or worsening suicidal ideation. Assess adherence to medication regimen. Assess for medication side effects. Continue to emphasize nutrition, physical activity, and caring for self. Minimize complexity of medication dosing (e.g., once daily or nightly, when possible).

Box 47-9 Discontinuation of Antidepressant Treatment Remission of symptoms for 6-12 months. Tapering of medications rather than abrupt cessation. Discussion of relapse risks and early warning signs of recurrence.

KEY TREATMENT All antidepressants are generally equally effective; selection is most often based on side effect profile, previous response, comorbid conditions, drug interactions, and cost (Arroll et al., 2009; Trivedi et al., 2006) (SOR: A). SSRIs, SNRIs, mirtazapine, and bupropion are first-line treatments for depression (Rush et al., 2006) (SOR: A). Antidepressant doses should be increased every 2 to 4 weeks until remission of depressive symptoms is achieved or side effects become intolerable (SOR: A). Treatment of depressive episodes ranges from 6 to 9 months to years, depending on the number of prior episodes, severity of episodes, and risk of relapse (AHCPR, 1999; Geddes et al., 2003) (SOR:A). Psychotherapy has proved effective in treating depression, either as monotherapy or combined with pharmacotherapy (de Maat et al., 2008; Thase, 1997) (SOR: A).

Initiation of Treatment Once a patient has been initiated on an antidepressant, dosing should be optimized to treat depressive symptoms to remission while minimizing side effects (Box 47-8). Patients should be monitored for improvement in their mood and their specific array of depressive symptoms. Continued use of measurement-based care tools, such as the PHQ-9 or QIDS, can aid in the objective assessment of improvement. Patients should be followed more frequently on initiation of treatment, increasing time between appointments as the patient improves. Monitoring for side effects, particularly those that patients may be reluctant to bring up spontaneously, such as sexual side effects, can improve adherence and the therapeutic alliance. Patients should also be monitored for any worsening of mood, increased irritability, impulsivity, insomnia, sudden switches into euphoria, or suicidal ideation. Such symptoms may suggest bipolar diathesis, in which case discontinuing the antidepressant and changing to mood stabilizing agents may be indicated. Antidepressant doses should be increased every 2 to 4 weeks until the patient shows a response, maximum dose is reached, or side effects limit further dose changes. Antidepressant doses should 1072

c ontinue to be pushed until remission is achieved, or the patient has undergone an adequate antidepressant trial, i.e., continuation of a therapeutic dose for at least 4 to 8 weeks (Nierenberg et al., 2000).

Continuation of Treatment As noted, physicians are encouraged to push treatment until symptoms remit, maximum doses are achieved, or side effects become intolerable. Once symptoms remit, medications should continue for 6 to 9 months because risk of relapse is greater if patients discontinue medications prematurely (AHCPR, 1999; Geddes et al., 2003). Patients who have had multiple episodes of depression should continue pharmacotherapy because lifetime relapse rates for such patients are 50% to 85% (Eaton et al., 2008), and risk of recurrence increases by 16% with each successive episode (Solomon et al., 2000). Ongoing treatment should also be considered for patients who experienced severe functional impairment, severe suicidal ideation, or serious suicide attempts.

Discontinuation of Treatment For patients who have achieved ongoing remission and want to discontinue their medications, withdrawal of treatment should be gradual and carefully monitored (Box 47-9). Timing of discontinuation often depends on a patient’s current life stressors and the potential consequences of depressive relapse (e.g., loss of new job, stress on recently repaired relationship). Antidepressants should be gradually withdrawn to minimize potential withdrawal syndromes and allow for rapid upward titration should depressive symptoms recur. Physicians should discuss early warning signs of relapse (insomnia, early-morning awakening, loss of interest in activities) and instruct patients to contact the physician should such symptoms recur. Risk of relapse is greatest in the first few months of discontinuing antidepressants, and thus a scheduled appointment in this period is often needed to


monitor for relapse. Patients who relapse after cessation of antidepressants should be restarted on their previous medication and again titrated to remission of symptoms.

Antidepressant Failure Patients who fail antidepressants should be carefully reevaluated, with reconsideration of medication adherence, adequacy of dosing and treatment duration, diagnosis, comorbid psychiatric illnesses, increased stressors, and unaddressed medical or substance comorbidities. Initial antidepressant failure may be relatively common; only one third of patients achieved remission after 12 to 14 weeks of treatment with citalopram in the STAR*D study (Trivedi et al., 2006). If a patient fails an adequate antidepressant trial, the next strategy is (1) switching to a different antidepressant, within the same class or across classes; (2) augmenting the existing antidepressant with a secondary agent; or (3) adding a second antidepressant to the first. Choice of strategy depends on patient preference, assessment of benefit from current antidepressant, current side effects, and psychiatric and medical comorbidities. Switching antidepressants is generally considered when the patient has had little to no response to the first agent or is having intolerable side effects. Across-class switches are most often considered as an initial strategy (e.g., SSRI to SNRI), although within-class switches may also prove useful (e.g., fluoxetine to sertraline). Across-class or intraclass switching may yield response rates of 20% to 50% (Thase, 2008b). In the STAR*D study, switching from citalopram to either bupropion SR, venlafaxine, or sertraline yielded remission rates of 18% to 25% (Rush et al., 2006). No clear guidelines exist as how best to cross-taper medications, although it is generally unwise to stop antidepressants abruptly because withdrawal syndromes may ensue. Medications with a short half-life, such as venlafaxine (immediate release) or paroxetine, have most often been associated with withdrawal syndromes. Typically, patients complain of flulike symptoms, electric-like shocks in the back of their heads, or dizziness (Taylor et al., 2006). Consideration of half-life and slow cross-tapers often yields the most tolerable switch. Augmentation strategies involve adding a second agent with no intrinsic antidepressant properties to the existing antidepressant. These are often considered when a patient has had a partial response to an antidepressant but has not reached remission, and switching to an alternate antidepressant may risk loss of existing response. The two best studied augmentation strategies to date are adding lithium and triiodothyronine (T3). Although many lithium augmentation studies are limited by methodologic considerations, response has been seen as quickly as 48 hours or as long as 2 to 4 weeks. Standard lithium levels of 0.5 to 1.0 mmol/L have most often been used. T3 augmentation has yielded similar results, if often better tolerated than lithium, usually with doses of 25 to 50 μg/day. Overall remission rates in patients unable to achieve antidepressant-alone remission range from 15% to 50% (Nierenberg et al., 2006). Atypical antipsychotic drugs have also been used as augmenting agents in nonpsychotic major depression, with beneficial results. Aripiprazole currently has an indication as an augmenting agent, at 2 to 15 mg daily. To date, no other atypical antipsychotic has an FDA indication as an augmenting agent, though a meta-analysis

of atypical antipsychotics as augmenting agents found their efficacy superior to placebo, with a number needed to treat (NNT) of nine for both response and remission (Nelson and Papakostas, 2009). Buspirone has also been used as an augmenting agent, as its 5-HT-1A receptor agonism may enhance SSRI response. In the STAR*D study, 30% of patients who failed to achieve remission taking citalopram went on to remit with the addition of buspirone, up to 60 mg daily (Trivedi et al., 2006). Combining two antidepressants to treat refractory depression is based on the theory that targeting a greater number of neurotransmitters will lead to improved antidepressant response. Common strategies include combining mirtazapine and venlafaxine, bupropion and SSRIs, or bupropion and SNRIs. Combining drugs of similar class (e.g., SSRI + SSRI or SNRI + SNRI) currently has few data to support its use. Venlafaxine combined with mirtazapine and citalopram plus bupropion SR were effective in the STAR*D study when patients failed to achieve remission on their current regimen. Adding bupropion to citalopram achieved a remission rate of approximately 30% in patients whose symptoms failed to remit after 12 weeks of citalopram therapy. The combination of venlafaxine plus mirtazapine was used in a highly treatment-refractory group (failed three previous medication trials) and achieved remission of symptoms in approximately 14% of patients (McGrath et al., 2006).

KEY TREATMENT Patients who fail antidepressants should be carefully reevaluated for medication adherence, adequacy of dosing and therapy duration, diagnosis, comorbid psychiatric illnesses, increased stressors, and unaddressed comorbidities (Trivedi et al., 2006) (SOR: A). Common strategies used when patients fail an initial antidepressant treatment are switching antidepressants (either within class or across classes) (Rush et al., 2006; Thase, 2008b), augmenting with other agents (lithium, T3, atypical antipsychotics) (Nierenberg et al., 2006; Trivedi et al., 2006), or combining different antidepressants (McGrath et al., 2006) (SOR: A).

Anxiety There is significant pharmacologic overlap between the treatment of depression and anxiety disorders. Most antidepressants are also effective antianxiety agents, or anxiolytics (see Table 47-3), thus simplifying treatment strategies when patients have both disorders. In addition, significant overlap also exists between medications that effectively treat GAD and panic disorder. Treatment recommendations for both GAD and panic will be explored separately in order to highlight some of the treatment differences between the two disorders.

Generalized Anxiety Disorder Antidepressants are generally considered first-line agents for treatment of GAD because of efficacy and safety, effectiveness in treating comorbid major depression, and absence of addictive or abuse potential, as seen with benzodiazepines. As a general rule, starting antidepressant doses for patients with GAD should be approximately half the lowest starting dose for treatment of depression; many experience a paradoxical worsening of their symptoms on antidepressant 1073

47


initiation if doses are high (see Table 47-2). Patients with anxiety disorders are typically more sensitive to antidepressant side effects (see Table 47-4), and thus starting at lower doses and titrating slowly will likely yield better results. The SSRIs and SNRIs are considered first-line treatments, with numerous studies demonstrating both efficacy and effectiveness (Hoffman and Mathew, 2008). A Cochrane review of antidepressant treatment of GAD that included paroxetine, sertraline, venlafaxine, and imipramine found a very large effect size, with NNT of only five patients for one patient to receive benefit, with no clear evidence of one antidepressant superior to another (Kapczinski et al., 2003). At present, the SSRIs escitalopram and paroxetine and the SNRIs venlafaxine and duloxetine are the only antidepressants with an FDA indication for GAD (see Table 47-3). No randomized controlled trials (RCTs) have yet supported the efficacy of fluoxetine or citalopram in the treatment of GAD, although their clinical use is based on the assumption that SSRIs exert a class effect and are likely equally effective. The SNRI desvenlafaxine may be effective but currently is indicated only for major depression. The TCAs, also effective agents for treating GAD, have been relegated to second-line treatment because of side effects (e.g., anticholinergic, sedative, orthostatic) and potential lethality in overdose. Imipramine has the strongest data to support its use in GAD (Kapczinski et al., 2003). Although used effectively in the treatment of anxiety disorders, monoamine oxidase inhibitors (MAOIs) have significant side effects (risk for hypertensive crisis, potential lethal interactions with other medications) and likely do not have a role in primary care and should be reserved for psychiatric practice. Mirtazapine has shown some efficacy in open-label trials (Gambi et al., 2005) but needs further study in RCTs to be considered a first-line agent in GAD. Bupropion has a less clear role in the treatment of anxiety disorders and may worsen rather than alleviate anxiety symptoms. However, a recent pilot study showed that bupropion XL had comparable anxiolytic efficacy with escitalopram in a 12-week, double-blind RCT and was well tolerated (Bystritsky et al., 2008). Bupropion may have a role in GAD treatment in the future but currently may be considered a second-line or third-line agent. Benzodiazepines are also extremely effective for treatment of GAD and offer the advantage of rapid effect. Onset of action is typically within hours, versus weeks with antidepressants. All benzodiazepines are theoretically equally effective in GAD, and thus selection of individual agents often involves comparing half-lives, metabolic pathways, and the presence or absence of active metabolites (particularly in patients with liver disease), and speed of onset of action. Benzodiazepines with shorter half-life result in the inconvenience of multiple daily dosing, the risk of rebound anxiety, and the common need to use as-needed doses as a “rescue” medication when symptoms are inadequately controlled. Medications such as clonazepam, with a long half life, or alprazolam XR, with a slower and more prolonged onset of action, may be more effective than drugs with shorter half-life, such as immediate-release alprazolam or lorazepam. Scheduled dosing of a benzodiazepine provides for a more consistent medication blood level and may also be a more effective approach than as-needed dosing. The duration of therapeutic effect for benzodiazepines is determined by the rate and extent of drug distribution (lipophilicity) and not necessarily by the rate of 1074

elimination. Benzodiazepines such as diazepam have a longer half-life than lorazepam, but because diazepam is more lipophilic, it has a faster onset of action and shorter duration of effect after a single dose (Schatzberg and Nemeroff, 2009). Drug elimination occurs in the liver through microsomal oxidation or glucuronide conjugation. Oxidation is sensitive to liver disease and certain medical conditions and medications (e.g., cimetidine), and therefore benzodiazepines metabolized through hepatic oxidation are more likely to show unpredictability than those metabolized via conjugation. Benzodiazepines such as temazepam, lorazepam, and oxazepam are cleared through hepatic conjugation and are safer and better tolerated when oxidative elimination has been altered. Even though benzodiazepines offer the advantage of rapid onset and effectiveness, other disadvantages have relegated them to second-line agents. Benzodiazepines pose a significant risk of dependency and withdrawal, are potentially lethal in overdose if mixed with other sedating agents (especially alcohol), and are ineffective in treating comorbid depression. Benzodiazepines also can impair attention and vigilance and cause dose-dependent anterograde amnesia, with limited effect on psychic symptoms, including worry (Hoehn-Saric et al., 1988). Benzodiazepines should generally be considered second- to third-line agents as monotherapy in GAD, although they are often used as adjunctive agents when initiating antidepressant treatment, to provide immediate relief of anxiety symptoms until antidepressant effects begin. Symptom severity and patient preference should be considered when deciding whether to use an antidepressant as monotherapy or to start a benzodiazepine with an antidepressant. A subset of patients may benefit from long-term treatment with both an antidepressant and a benzodiazepine. Nonbenzodiazepine and nonantidepressant treatment may also be effective in the treatment of GAD, especially for patients with mild to moderate symptom severity. Buspirone, an azapirone that exerts 5-HT-1A receptor agonism, carries an FDA indication for GAD. Buspirone appears useful in the treatment of GAD, particularly for patients who have not yet received a benzodiazepine (Chessick et al., 2006). In clinical practice, buspirone can be used as monotherapy in patients with mild to moderate symptoms, and it is often considered an alternative to benzodiazepines as an augmenting agent to antidepressants. Hydroxyzine, an antihistaminic agent, also carries an FDA indication for GAD and has shown efficacy in RCTs (Llorca et al., 2002). Its sedative properties and lack of efficacy in comorbid disorders have relegated hydroxyzine to a second-line agent. Interestingly, a meta-analysis of effect sizes in pharmacotherapy of GAD recently showed that hydroxyzine had a larger effect size (0.45) than SSRIs (0.36) (Hidalgo et al., 2007). At present, hydroxyzine may be considered an alternative to benzodiazepines when no comorbid illnesses are present as monotherapy. Recent studies of pregabalin have also shown efficacy in the treatment of GAD. In the meta-analysis cited, pregabalin was found to have the largest effect size (0.5) of all agents (SSRIs, SNRIs, benzodiazepines, azaspirones, antihistamines, complementary/alternative agents). The effect size of pregabalin was determined from two large RCTs. In addition, pregabalin was found to be effective in relapse prevention compared to placebo over a 6-month trial (Feltner et al., 2008). Beta blockers such as propranolol and pindolol have also been used in the treatment of GAD. Although these can block the physiologic effects


of anxiety, such as sweating and increased heart rate, beta blockers appear ineffective in treating the underlying emotional component of anxiety, and little empiric evidence supports their use in GAD at present.

KEY TREATMENT SSRIs and SNRIs are considered first-line treatments for generalized anxiety disorder, with starting dose typically half that used in depression (Hoffman and Mathew, 2008) (SOR: A). TCAs are effective in treatment of GAD (SOR: A), but their side effect profile and potential lethality have relegated them to second-line agents (Kapczinski, et al., 2003). Benzodiazepines offer the advantage of rapid effect and proven efficacy (Chessick et al., 2006; Schatzberg and Nemeroff, 2009) (SOR: A), but carry risk of abuse and dependence. Other agents for treatment of GAD include hydroxyzine (Llorca et al., 2002) (SOR: A), buspirone (Chessick et al., 2006) (SOR: B), and pregabalin (Feltner et al., 2008) (SOR: B). Maintenance treatment of GAD reduces the likelihood of relapse (Thuile et al., 2009) (SOR: B).

Panic Disorder Similar to treatment of GAD, SSRIs, SNRIs, TCAs and benzodiazepines have all been found to be effective for the treatment of panic disorder. Effectiveness of these agents appears relatively equal, and thus selection of a particular agent is most often based on tolerability, cost, ability to treat comorbid disorders, potential for abuse and tolerance, and patient preference. First-line agents to treat panic are most often SSRIs and SNRIs. Fluoxetine, paroxetine, sertraline, and venlafaxine all have FDA indications for panic disorder (see Table 47-3), although all the SSRIs have data to support their use (Otto et al., 2001). The SNRIs duloxetine and desvenlafaxine do not currently have large-RCT evidence to support their use in panic disorder but may have efficacy based on class effect. TCAs are also as effective in treating panic as SSRIs, but are less well tolerated due to their anticholinergic and antihistaminic side effects (Bakker et al., 2002). Both imipramine and clomipramine have the most data to support their use in panic disorder (APA, 2009). Because of tolerability and toxicity in overdose, TCAs are second-line agents for panic. Benzodiazepines offer several advantages over antidepressants in the treatment of panic, including rapid onset, asneeded dosing schedules, and relief of insomnia and somatic symptoms (Bruce et al., 2003). Similar to use in GAD, selection of a particular benzodiazepine is based on half-life, speed of onset of action, presence or absence of active metabolites, and metabolic pathways (particularly in patients with liver disease). All benzodiazepines are likely equally effective in treating panic, although in clinical practice, higher-potency benzodiazepines (e.g., alprazolam, clonazepam, lorazepam) are used more often than lower-potency drugs (e.g., oxazepam). Clonazepam and alprazolam both are FDA approved for panic disorder, and some clinicians prefer clonazepam to alprazolam because of clonazepam’s longer half-life, less frequent dosing, and slower onset of action. Lorazepam and diazepam do not have an FDA indication for panic, but seem to be effective agents in RCTS and clinical practice (Mitte et al., 2005). Benzodiazepines may be considered as first-line monotherapy when no comorbid conditions exist with panic

disorder. Agents with rapid onset (alprazolam, lorazepam) may be preferred if taken on an as-needed basis or used as a rescue medication. However, shorter-acting agents can introduce problems with interdose rebound anxiety or more difficulty with adherence to multidose regimens. Agents with longer half-life, such as clonazepam and alprazolam XR, may be scheduled once or twice daily to provide more even coverage throughout the day, but do not provide immediate relief if taken on an as-needed basis. Although benzodiazepines can bring quick relief from panic symptoms, their side effect profile and risk of dependency, abuse, and withdrawal must be considered when deciding on their use. Common side effects include sedation, fatigue, ataxia, slurred speech, memory impairment, and weakness. Geriatric patients taking benzodiazepines may be at higher risk for falls and fractures (Stone et al., 2008). Patients with a substance abuse history may need to be monitored closely for signs and symptoms of abuse; patients actively abusing substances should probably not be prescribed benzodiazepines. For many of these patients, discussing clear expectations that prescriptions will not be rewritten or refilled before a set date can limit later conflicts and improve treatment adherence. Evidence for the use of beta blockers in panic disorder is sparse. Beta blockers have been used to reduce the somatic symptoms of panic attacks, such as palpitations, but do not seem to be effective in overall treatment of panic disorder.

KEY TREATMENT SSRIs, SNRIs, TCAs, and benzodiazepines have all been found to be effective in the treatment of panic disorder (Otto et al., 2001) (SOR: A). First-line agents for panic disorder are SSRIs and SNRIs, with starting doses typically half that for depression (APA, 2009) (SOR: A). Benzodiazepines can be used as first-line agents when no comorbid psychiatric issues are present, including issues of substance abuse and dependence (Mitte et al., 2005) (SOR: A). Maintenance treatment of panic disorder has been shown to reduce the likelihood of relapse (Thuile et al., 2009) (SOR: B).

Continuation of Treatment in Anxiety Disorders Treatment for anxiety disorders should be continued for 6 months to a year; a more definitive time frame is not yet clear. Results from long-term RCTs of antidepressants in anxiety disorders indicate that maintenance treatment significantly reduces the risk of relapse, whatever the disorder (Thuile et al., 2009). Decisions on length of treatment are generally made on a case-by-case basis, taking into account the risk/benefit ratio of treatment versus no treatment. If the decision is to discontinue treatment, the medication should be tapered at a rate that takes into account its pharmacokinetics and whether the patient experiences withdrawal symptoms (see Box 47-9).

Other Considerations Antidepressants and Suicidal Ideation In 2004 the FDA added a black-box warning to all antidepressants indicating that the use of antidepressants in children, adolescents, and young adults under 25 years of age 1075

47


increased the risk of suicidal thinking and behavior. The warning on antidepressants was based on an analysis of 372 clinical trials involving 11 antidepressant medications, noting an increase in the number of patients who experienced an increase in suicidal ideation and behavior, although no increase in actual suicides was observed. Further analysis of the FDA data revealed a strong age-dependent relationship, such that the greatest risk was in patients younger than 25. In clinical terms, four additional patients in 1000, age 18 to 24 years, would be expected to experience suicidal ideation or behavior as a result of taking antidepressants, and an additional 14 patients in 1000, under age 18, would be expected to experience worsening. Patients older than 30 showed a reduction in suicidal ideation as a result of taking antidepressants, with a reduction of 6 patients of 1000 in adults over 65. The net effect of antidepressant use in patients age 25 to 64 seems moderately protective against suicidal ideation and more strongly protective for adults age 65 and older (Levenson and Holland, 2006). Antidepressants should be used cautiously in patients under age 25, with close monitoring for worsening of mood or thoughts of suicide, particularly in the days and weeks after the drug is initiated. For the majority of depressed patients, the beneficial effects of antidepressants greatly outweigh the risks (Libby et al., 2007).

e quivalent to TCAs in treating patients with depression, although the most robust findings have been shown with parenteral administration of the drug. Studies using the oral form have yielded more variable results. In adjunctive use with antidepressants, only one open-label study has been published to date. SAM-e has been shown to be safe and well tolerated thus far (Papakostas, 2009). Omega-3 fatty acids have a variety of health benefits and may be helpful as augmenting agents in the treatment of major depression. The best-studied agents are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Findings in depression are limited by variability in study design and small sample sizes, although the majority of evidence favors a positive effect in the treatment of mood disorders (Freeman, 2009). At present, little robust evidence supports the efficacy of CAM agents in the treatment of anxiety disorders. Kava (Piper methysticum) has preliminary evidence of efficacy in GAD, but further testing is needed to determine its side effects and potential for hepatotoxicity (Sarris and Kavanagh, 2009). A meta-analysis found no statistically significant difference between kava and placebo (Hidalgo et al., 2007). Given the paucity of current evidence, caution should be used when considering kava as a therapeutic agent.

Nontraditional Therapy

Electroconvulsive Therapy

Interest in complementary and alternative medicine (CAM) for health disorders has been growing steadily in the last several decades. As a result, a greater number of alternative or complementary agents are being tested in more methodologically rigorous ways, allowing greater scientific assessment of such treatments. Survey evidence suggests that as many as 40% to 60% of patients may be taking CAM therapies, although patients often do not disclose such use to their physicians (Elkins et al., 2005). In addition, because production of alternative agents is unregulated, variability in product strength, dosing, and purity is common, which in turn likely affects the predictability of their outcomes. Given the widespread use of CAM agents and patients’ apparent reluctance to spontaneously disclose such use to their providers, it is incumbent on physicians to inquire about such use. The majority of CAM treatments have been used to treat depression, including St John’s wort (Hypericum perforatum), S-adenosyl-methinionine, and omega-3 fatty acids. In a Cochrane review of St John’s wort for treatment of major depression, great heterogeneity was found among the 29 analyzed trials (Linde et al., 2005). St John’s wort was found to be superior to placebo and similarly effective as standard antidepressants, but findings were more favorable to St John’s wort studies from German-speaking countries, where use of the extract has a long tradition. The more positive results may be caused by physician expertise with the medication, patient selection, or flawed methodologies in some research. The larger, placebo-controlled studies have yielded mixed results, although compared to antidepressants, St John’s wort has generally been better tolerated (Shelton, 2009). S-Adenosyl-l-methionine (SAM-e), a dietary supplement, has been used to treat a variety of illnesses, ranging from major depression to osteoarthritis to liver disease. Clinical trials have shown SAM-e to be superior to placebo and

Electroconvulsive therapy (ECT) involves a brief electrical stimulation of the brain while the patient is anesthetized, inducing a seizure. ECT remains the most effective treatment for depression (UK ECT Group, 2003), although the stigma surrounding the treatment, misinformation about its practice, side effects, and cost have often made it a treatment of last resort. Although occasionally used as first-line therapy for severe depression, ECT is often used for multitreatmentrefractory patients, those with psychotic depression, suicidal patients (imminent), and depressed patients with compromised oral intake. A typical course is six to 20 treatments, with patients receiving ECT three times a week during the acute phase, gradually increasing the time between treatments as improvement becomes apparent. After acute treatment, patients are often returned to antidepressant therapy, although medication efficacy after ECT does not appear to be enhanced (Kellner et al., 2006). Physicians should be aware that ECT is safe, well tolerated, humane, and effective.

1076

Other Treatments

Vagus Nerve Stimulation and Transcranial Magnetic Stimulation Vagal nerve stimulation (VNS) involves the surgical implantation of a nerve stimulator for the left vagus nerve at the cervical level and has been approved for treatment of refractory depression. VNS is not an acute treatment, but has shown some long-term benefit for depressed patients (George et al., 2005). Transcranial magnetic stimulation (TMS) involves the introduction of repetitive magnetic impulses to the right prefrontal cortex in a series of treatments over several weeks. TMS is approved for the treatment of unipolar depression for patients who have failed one trial of antidepressants or for those patients who have exhibited marked intolerance to antidepressants (O’Reardon et al., 2007).


Psychotherapy In addition to pharmacologic interventions for depression, panic disorder, and GAD, psychotherapy continues to be an effective tool used by psychiatrists and psychotherapists for treating mood and anxiety disorders. Although primary care physicians will not administer such treatments, it is important to be aware of general psychotherapeutic concepts and strategies. Several types of therapy have strong evidence supporting their efficacy in treating both depression and anxiety disorders, including cognitive-behavioral therapy, interpersonal therapy, psychodynamic psychotherapy, problem-solving therapy, and supportive therapy (Cuijpers et al., 2008). Some patients may prefer to begin treatment with medications alone, whereas others may prefer only psychotherapy or a combination. Combined pharmacologic and psychotherapeutic interventions have generally been shown to be superior to either approach alone in trials for both anxiety disorders and depression (Furukawa et al., 2007) (Pampallona et al., 2004).

illnesses. Patients who experience refractory depression or psychotic depression are best treated by specialty providers. Patients with bipolar disorder should be referred as well, especially those suffering from bipolar depressions, as they are often especially difficult to treat, usually require complex polypharmacy, and worsen with inappropriate treatment. Patients requesting or needing psychotherapy or behavioral therapy may be referred to a mental health provider.

Summary For the majority of depressed patients, the beneficial effects of antidepressants greatly outweigh the risks. CAM treatments for depression may be beneficial for some patients, but study methodology limits their generalizability. ECT is still considered the most effective treatment for severe depression. VNS and TMS are emerging therapies for the treatment of depression.

KEY TREATMENT

Referral to Mental Health Providers Which patients should be referred to mental health providers? Referrals may be made because of patient preference, severity of illness, or because of the complexity of comorbid

Psychotherapy is an important and effective treatment strategy for both depression and anxiety. Psychotherapy combined with pharmacotherapy often yields superior results to either treatment alone (Furukawa et al., 2007; Pampallona et al., 2004) (SOR: A).


Web Resources Patient Resources National Institute of Mental Health www.nih.nimh.gov Provides excellent up-to-date information on the symptoms, causes, course, and treatment of a number of illnesses. Provides numerous lists and links to resources. Anxiety Disorders Freedom From Fear freedomfromfear.org National non-profit mental health advocacy organization focused on anxiety and depressive disorders. The Obsessive-Compulsive Foundation www.ocdfoundation.org Provides information and resources on obsessive-compulsive disorder and other mental health diagnoses.

Support for Patients, Family, and Friends American Foundation for Suicide Prevention www.afsp.org Leading national non-profit dedicated to understanding and preventing suicide through education and research, and to reaching out to people with mood disorders and those impacted by suicide. The Federation for Families for Children’s Mental Health www.coloradofederation.org The mission of the Federation is to promote mental health for all children, youth and families. The website has numerous links to resources, articles, books, and support groups.

Healthy Minds www.healthyminds.org Site created by the American Psychiatric Association to provide education and resources on mental health issues. National Alliance on Mental Illness www.nami.org Grass-roots, self-help, support, and advocacy group for people with severe mental illnesses, their family members, and friends. Depression and Bipolar Support Alliance www.dbsalliance.org Provides education to patients and families about mood disorders; advocates research funding, improving access to care, fostering self-help, and decreasing public stigma of these illnesses. Depression Is Real www.depressionisreal.org Provides information and resources about depression. Madison Institute of Medicine www.miminc.org Provides information and resources on mood disorders, anxiety disorders, and dementias. WebMD Depression www.webmd.com/depression Provides information on diagnosis and treatment of mood disorders.

1077

48 CHAP T E R Delirium and Dementia David A. Smith and David A. Brechtelsbauer

Chapter contents Delirium Clinical Features Etiology Diagnostic Process Prevention Treatment Natural History of Delirium

1078 1078 1079 1079 1081 1081 1082

Dementia and delirium are organic brain syndromes characterized by global cognitive dysfunction. Delirium is the recognized terminology for what has also been called acute confusional state, acute brain syndrome, acute cerebral insufficiency, and toxic-metabolic encephalopathy. Dementia has commonly been called “senility” or the insufficiently specific “organic brain syndrome.” It may be useful to conceptualize delirium as acute brain failure and dementia as chronic brain failure.

Delirium Clinical Features Key Points • D elirium is characterized by an acute change from usual function and cognition. • Level of consciousness varies, often dramatically, in patients with delirium. • Delirium may be hyperactive, hypoactive, or mixed. • Delirium is often overlooked or misdiagnosed. • Delirium worsens prognosis and increases length of stay and likelihood of nursing home placement.

Delirium is an acute disorder of global cognitive function involving attention, consciousness, orientation, memory, sensory perception, executive function, and behavior. Misperceptions of any of the senses may occur, but auditory and visual disturbances manifesting as suggestible hallucinations or illusions are common. For example, the delirious patient may interpret spots on the floor tiles as bugs or the sound of the wind as whispering. Delirious patients have abnormal visual perception compared to cognitively normal and demented patients that is independent of the severity of cognitive impairment (Brown et al., 2009). ©2011 Elsevier Ltd, Inc, BV DOI: 10.1016/B978-1-4377-1160-8.10048-8

Dementia Clinical Features Diagnostic Process Common Types of Dementia Less Common Causes of Dementia Behavioral and Psychiatric Symptoms Accompanying Dementia Care Settings for the Dementia Patient

1082 1082 1083 1084 1088 1089 1089

Delirium cases can be grouped into hyperactive, hypoactive, and mixed subtypes on the basis of psychomotor behavior (Meagher et al., 2008). It has been suggested that the hypoactive subtype is more often seen in elderly persons and with delirium caused by hypoxia, metabolic abnormality, and anticholinergic drugs, whereas the hyperactive subtype is more common in substance intoxication and withdrawal states. Cognitive impairment and generalized slowing of the electroencephalogram (EEG) are similar in hypoactive and hyperactive subtypes. Delirium can occur at any age, although advanced age is an independent risk factor. Rather than considering chronologic age in assessing risk, a family physician may best consider biologic age and frailty. Delirium is often overlooked or misdiagnosed. This lack of diagnostic clarity is concerning given that, independent of other variables, delirium worsens prognosis (Fong et al., 2009; McAvay et al., 2006), often leading to chronic decreased function and cognition. Only 15% of delirious hospitalized patients will regain their baseline function by discharge, and less than half will return to prior function at 6 months (Khan et al., 2009). Delirium increases hospital length of stay by 5 to 10 days (Siddiqi et al., 2006), as well as the likelihood of nursing home placement (Inouye et al., 1998). Finally, mortality increases by 10% to 37% in hospitalized elderly patients (McCusker et al., 2002; Siddiqi et al., 2006). Approximately 40% of patients with delirium during hospitalization who survive to discharge will die within 1 year (Inouye, 2006). Delirium prevalence and incidence vary greatly across settings of care and populations served. From 10% to 15% of hospitalized elderly patients have delirium on admission, and another 5% to 10% develop it during their stay. More than half of long-term care residents will exhibit delirium on hospital admission. Postsurgical patients (e.g., hip fracture, cardiac surgery) and elderly patients cared for in an intensive care unit (ICU) are at particularly high risk (Khan et al., 2009).

Delirium and Dementia

Etiology Key Points • C entral nervous system immaturity in children and CNS disease in elderly persons may explain the increased prevalence of delirium in these two groups. • Children generally have a more acute onset of delirium, but a less fluctuating course, than adults. • Delirium is thought to be caused by an acute cholinergic deficit; other neurotransmitter disturbances are also probably involved.

A stress-diathesis model has been proposed to explain the risk of delirium, depending on the severity of an insult to brain function and the vulnerability of the brain because of immaturity in children and central nervous system (CNS) disease or degenerative disorders most common in elderly persons. This helps explain the highest risk of delirium in the elderly population and more frequent occurrence in children than in young and middle-aged adults. Although the phenomenology of delirium in adults and in elderly persons differs only in the severity of cognitive symptoms and resilience in recovery, the course and symptomatology in childhood are different. Childhood delirium is often associated with febrile illness and from CNS-toxic medications (anticholinergics) (Lenntjens et al., 2008). Delirium in a child is more likely to have a very acute onset, but a less fluctuating course with less disruption of the sleep-wake cycle, than in adults. Cognitive deficits may be less pronounced in children, whereas hallucinations, delusional thinking, and labile mood may be more pronounced. The different array of causes of delirium in children and adults might explain these differences. In both children and elderly patients with dementia, problematic behaviors caused by delirium are often falsely attributed to irritability associated with illness or oppositional behavior toward caregivers. When a child cannot be comforted by a parent, delirium should be suspected. The remainder of this discussion focuses on delirium in the elderly patient.

Diagnostic Process Key Points • T ools for diagnosing and managing delirium include Confusion Assessment Method and Memorial Delirium Assessment Scale. • Dementia is the strongest risk factor for development of delirium. • Diagnostic testing needs to be informed by a thorough history and careful physical examination.

Diagnostic criteria for delirium are adapted from the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM IV-TR, 2000) (Box 48-1). Given the high prevalence of delirium in certain health care settings and clinical circumstances, diagnosis should not depend solely on a high index of suspicion. Formal evaluation of mental status to detect delirium or dementia should become part of routine assessment of elderly patients presenting with a change of condition. This not only fosters appropriate preventive and therapeutic interventions, but also alerts the interdisciplinary team (IDT) to plan care to ensure patient and staff safety, specific patient and family education, carefully considering cognition and function at discharge planning.

Systemic inflammation

Drugs inducing delirium

Physiologic or metabolic disease

Increased CNS inflammatory cytokines

Impaired CNS neurotransmission*

Impaired cerebral metabolism

DELIRIUM

*More vulnerable in immature or already impaired brain. Figure 48-1 Theoretic etiologic hypothesis for delirium.

Neurochemical Hypothesis Cholinergic transmission in the CNS has a major role in cognition and attention, and an acute cholinergic deficit exists in delirium. Dopaminergic transmission is increased in delirium, and this or the imbalance between cholinergic and dopaminergic systems may be etiologic. Disturbances in other neurotransmitters are hypothesized, perhaps explaining subtypes or variations in presentations of delirium. Serotonin may be increased in delirium associated with serotonin syndrome and in hepatic encephalopathy, but decreased in delirium from other causes. Glutamate and γ-aminobutyric acid (GABA) are believed to be increased in alcohol withdrawal and hepatic encephalopathy. Melatonin may be increased or decreased in delirium, which may explain hypoactive and hyperactive subtypes. Norepinephrine may be increased in delirium associated with anoxia and in hepatic encephalopathy. Inflammation may also play a role in causing delirium, either by a direct neurotoxic effect or by causing disturbances in the neurotransmitters. Figure 48-1 depicts a theoretic explanation for the etiology of delirium.

Box 48-1 Diagnostic Criteria for Delirium (DSM IV-TR) A. D isturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention. B. A change in cognition (e.g., memory deficits, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia. C. The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day. D. There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a general medical condition, a substance intoxication, or a substance withdrawal; is the result of multiple etiologies; is caused by an etiology other than these (e.g., sensory deprivation); or cannot be determined. Modified from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.

1079

48


Several standardized instruments have been developed to assess for delirium and monitor severity. The Confusion Assessment Method (CAM) is based on DSM IV-R criteria and has 94% to 100% sensitivity and 90% to 95% specificity, with good interrater reliability when used with formal cognitive testing and administered by trained interviewers (Inyoue et al., 1990). Once diagnosed, the 10-item Memorial Delirium Assessment Scale is useful to monitor severity (Breibart et al., 1997). Other scales are used in specific settings (e.g., ICU). Given the fluctuating course of delirium, it is essential to perform monitoring frequently.

History and Physical Examination The etiology of delirium is often multifactorial. Therefore the history and physical examination must be detailed and exhaustive; stopping on discovery of one cause is inadequate. The history relevant to delirium is largely a search for risk factors. Risks may be considered as predisposing factors (vulnerability of brain) and precipitating factors (insults to brain). Dementia is the strongest risk factor for delirium (Cole, 2004); two thirds of elderly patients with delirium will also have dementia. This relationship is so strong that if delirium is diagnosed in an elderly person without known dementia, an investigation should be made once the delirium has resolved. Severe illness, infections, sensory deprivation, medications, and substances of abuse causing either toxicity or withdrawal states can precipitate delirium. Use of medications confers risk both by number and by drug interaction. The risk of delirium is especially high in elders who have three or more medications initiated within a 24-hour period during hospitalization. Box 48-2 is a compilation of predisposing and precipitating risks for delirium, and Boxes 48-3 and 48-4 list medical illnesses and drugs, respectively, that can cause or contribute to delirium. A comprehensive physical examination should be completed, emphasizing the neurologic exam, including objective tests of cognition (see Diagnostic Process for dementia). Box 48-2 Risk Factors for Delirium

Predisposing Factors Sensory impairment Immobility (functional and iatrogenic) Psychological stress Cognitive impairment (dementia, MCI) Lower educational status Advanced age Past history of delirium, CVA, falls, or neurologic disease Multiple medical comorbidities Male gender Polypharmacy

Precipitating Factors Medical conditions (see Box 48-3) Medications (see Box 48-4) Environmental change or stress Pain Profound sleep deprivation MCI, Mild cognitive impairment; CVA, cerebrovascular accident (stroke).

1080

An investigation for focal neurologic signs should be done. For example, asterixis (flapping of maximally dorsiflexed hands) is characteristic of hepatic encephalopathy, but not unique to it. Tremor may be present in withdrawal states, as are signs of autonomic dysfunction (hypertension, tachycardia, mydriasis, sweating). Nuances of the history and physical examination are essential to hypothesizing the cause(s) of delirium and to inform decisions to order laboratory and other diagnostic studies and plan specific therapy. Broadly testing without guidance from the history and physical exam is particularly inefficient in determining the cause(s) of delirium. Neuroimaging is of extremely low yield unless done to investigate focal neurologic findings. Furthermore, history of a fall with head trauma and even the finding of a subdural hematoma on computed tomography (CT) might not fully explain a patient’s delirium as caused only by acute brain injury if, for example, the fall was caused by a preexisting delirium from recent initiation of a medication. Other investigations may be needed in specific situations. An EEG is not routinely needed but is helpful in diagnosing

Box 48-3 Medical Conditions that May Cause or Contribute to Delirium Cardiovascular disease Arrhythmia Congestive heart failure Myocardial infarction Shock Cerebrovascular accident (stroke) Hypertensive encephalopathy Central nervous system (CNS) neoplasm Infections CNS infection Pneumonia Sepsis Urinary tract infection Metabolic disorders Acidosis/alkalosis Anemia Endocrinopathies Fluid and electrolyte imbalance Hepatic failure Renal failure Nutrition related General Specific deficiencies (e.g., thiamine) Pulmonary disorders Hypoxia Hypercarbia Sensory deprivation Hearing Vision “ICU psychosis” Trauma Head Other severe injury Surgery


toxic encephalopathy, and it is essential in a patient with suspected nonconvulsive status epilepticus.

Prevention Key Point

•

revalence of delirium in high-risk settings mandates P uniform implementation of unit-wide or facility-wide preventive programs.

KEY TREATMENT Geriatrics consultation, nurse-led interdisciplinary programs, and preemptive low-dose haloperidol decreased delirium severity (but not incidence) in randomized controlled trials (RCTs) or pre/post trials (Kalisvaart et al., 2005; Marcantonia et al., 2001; Milsen et al., 2001) (SOR: B).

Treatment Key Points

An evaluation of risk allows caregivers to apply preventive strategies to avoid development of delirium in high-risk individuals (Box 48-5). However, given the high prevalence in hospitalized elderly patients and in long-term care patients, and the benign nature of many of the strategies for prevention, a standardized facility-wide prevention program may be more appropriate and effective. Prevention involving nonpharmacologic strategies attempts to maintain or normalize sleep patterns, stimulate physical and mental activity consistent with the elderly person’s function, maintain or restore orientation to time/person/place, avoid or correct fluid and electrolyte disturbances, maximize the accuracy of sensory perceptions, and minimize the use of catheters and physical restraints. Benzodiazepines and anticholinergic medications are best avoided when possible. Appropriate pain relief must be balanced with the risk of narcotic-induced delirium. Meperidine creates high risk from short analgesic effect but prolonged elimination of a nonanalgesic but CNS-toxic metabolite. Trials of proactive geriatrics consultation (Marcantonia et al., 2001), nurse-led IDT protocol-based interventions (Milsen et al., 2001), and preemptive low-dose haloperidol (Kalisvaart et al., 2005) have demonstrated decreases in delirium severity in elderly patients hospitalized for repair of hip fractures.

Box 48-4 Drugs that May Cause or Contribute to Delirium Antiarrhythmics Anticholinergics Antidepressants Antiemetics Antiepileptics Antihistamines Antiparkinsonian agents Antipsychotics Antineoplastic agents Anxiolytics Centrally acting antihypertensive agents Corticosteroids Mood stabilizers Muscle relaxants Nonsteroidal anti-inflammatory drugs Opioid analgesics Sedative-hypnotics From American Medical Directors Association. Delirium and Acute Problematic Behavior Clinical Practice Guideline. Columbia, Md, AMDA, 2008.

• N onpharmacologic management plans should be considered first when treating delirium. • Indications for pharmacotherapy include delirium-induced behaviors that create a danger to the patient or others, or that interfere with necessary medical therapy. • Fluctuating nature of delirium makes assessment of treatment efficacy difficult. Assessments must be objective and repeated frequently. Repeat assessment to judge drug efficacy should be consistent with time required for drug to reach steady state.

Treatment of delirium begins with maximized effort to apply strategies outlined in Box 48-5. Identifying and treating one or more potential causes of delirium are equally important (e.g., correcting fluid and electrolyte imbalance, treating an infection and discontinuing medications conferring risk). Many delirium-induced behaviors respond well to nonpharmacologic interventions. For example, a delirious elderly patient with repetitive vocalizations disturbing others should be managed by

Box 48-5 Prevention and Treatment Strategies for Delirium 1. P rovide reassurance and education. 2. Optimize orientation. Minimize potentially ambiguous stimuli (e.g., overhead pager). Permit visitation (overnight family stay). Minimize room/facility transfers. Ensure consistent staff assignment. Provide clear instructions. Use frequent eye contact. 3. Optimize vision and hearing. 4. Optimize nutrition and fluid intake. 5. Optimize pain management, 6. Optimize mobility within patient’s limitations, Minimize restraints and catheter use. Maximize independent function (e.g., grooming). 7. Optimize sleep hygiene. Ensure consistent hour of retirement. Use bright light during day, with dark, quiet nights. Prevent nocturia. Provide pre-retirement routine (warm milk/herb tea, relaxation techniques, back massage). Avoid sedative-hypnotics. 8. Provide proactive medication management. Avoid drugs that typically cause delirium. Minimize polypharmacy.

1081

48


protecting others from the noise, not by sedating the delirious patient. Having a family member or sitter stay with a restless patient is better than use of physical or chemical restraints. Pharmacologic treatment becomes necessary when patients have delirium-induced behavior that makes them a danger to self or others, or that interferes with needed medical care (e.g., maintaining bed rest after major surgery, maintaining catheter integrity). Hypoactive delirium might warrant treatment to improve oral intake of food, fluids, and medication or to avoid the medical consequences of inactivity. Additionally, some patients will require treatment for the confusion or hallucinations causing anxiety and fear. Both agitation in hyperactive delirium and lethargy in hypoactive delirium increase the risk for malnutrition and dehydration, aspiration, pressure ulcerations, and deep venous thrombosis or pulmonary embolism. The goal of pharmacologic management should be correction of neurochemical abnormalities, not simply sedation. No medications are approved by the U.S. Food and Drug Administration (FDA) for treatment of delirium. Benzodiazepines are first-line therapy in patients with delirium induced by alcohol and sedative withdrawal. Antipsychotics are generally considered the drugs of choice in patients with most other types of delirium requiring pharmacologic management. The mode of action for antipsychotics in delirium is probably antagonism of dopamine and the resultant increase in acetylcholine. The choice of antipsychotic should be individualized based on suspected etiology, target symptoms, and patient susceptibility to adverse drug reactions (ADRs) because of age and comorbid conditions. The profile of antipsychotics regarding risk of cardiovascular events and death, QTc prolongation, anticholinergic effects, sedation, hypotension, and resulting glucose intolerance and movement disorders must be considered when choosing a drug. Higher doses and longer duration of therapy increase the risk of ADRs, as do age, female gender, and preexisting mood disorders or dementia. Delirious patients, particularly the elderly, often respond to fairly brief courses of low doses of antipsychotics, which decreases the chance of adverse side effects. Benzodiazepines are not recommended, but if used, low doses of short– half-life products (loratzepam, oxazepam) are preferred in elderly patients. Occasionally, methylphenidate is tried in hypoactive delirium. Delivery of medication to a delirious patient can be difficult; rapidly dissolving oral formulations are useful when cooperation with tablets or capsules is problematic. Depot injections of antipsychotics have no role in the treatment of delirium. The fluctuating course of delirium makes evaluation of drug therapy difficult. Monitoring of mental status and behavior throughout the day using objective measures is required. The use of any of the recognized pharmacologic treatments for delirium risks further impairment of cognitive function, thereby confounding monitoring because the observer has little to differentiate an inadequate response to therapy (and need for uptitration), worsening of the delirium per se, or worsening of cognition from an adverse drug effect, compounding the original delirium. When treating delirium, the family physician should employ nonpharmacologic strategies, medicate only when 1082

necessary, and use monotherapy. Adjust dose to age/body weight/composition and renal/hepatic function; avoid asneeded dosing; and titrate dose based on repeated objective assessments of delirium severity at intervals consistent with the time necessary for the drug to reach steady state. Treatment for 7 to 10 days after symptoms resolve is usual.

KEY TREATMENT Benzodiazepines are indicated for the treatment of alcohol withdrawal seizures (SOR: A) but are not recommended for treatment of non-alcohol-related delirium (SOR: B) (Cochrane Review). Haloperidol (1 pack/day). • Smokers who are also hypertensive have a 20 times greater stroke risk. • Risk of CVA declines rapidly after smoking cessation, and at 5 years is the same as for a nonsmoker.

Stroke (CVA) is the third most common cause of death in the United States. Although hypertension is the greatest risk factor for stroke, cigarette smoking is also significant. The incidence of stroke in smokers is two to four times higher than in nonsmokers. Among those screened in the Multiple Risk Factor Intervention Trial (MRFIT), smokers had twice the risk of a nonhemorrhagic stroke, and smoking was strongly associated with all forms of stroke (Neaton et al., 1993). The risk of stroke increases in proportion to the amount of smoking. Those who smoke more than 40 cigarettes/ day have twice the stroke risk of those who smoke less than 10 cigarettes/day. Compared with women who have never smoked, the risk of stroke increases 2.2-fold in women smoking 1 to 14 cigarettes/day and 3.7-fold in women 1111

50

Nicotine Addiction

s moking 25 or more cigarettes/day (Colditz et al., 1988). Noting a clear dose-response relationship, Bonita and associates (1986) found a threefold increase in the risk of stroke in smokers versus nonsmokers (see eFig. 50-1 online). The risk is 5.6 times higher in persons smoking more than one pack daily. Cigarette smokers who are also hypertensive have a 20-fold increased risk of stroke (US Surgeon General, 2004). Sclerosis of the carotid arteries is directly proportional to the amount of smoke exposure. Smoking increases the risk of ischemic heart disease and cerebrovascular disease regardless of the level of serum cholesterol. Low cholesterol level did not protect against smoking-related arteriosclerotic cardiovascular disease in patients in South Korea, where the prevalence of smoking is among the highest in the world (72% of men) (Jee et al., 1999). Smoking may increase the likelihood of thrombosis by increasing serum fibrinogen, enhancing platelet aggregation, and increasing blood viscosity. The risk of stroke declines rapidly after cessation of smoking. After 5 years, risk of CVA is at the level of nonsmokers, which emphasizes that “it is never too late to quit,” no matter how long the patient has been smoking.

Other Diseases and Conditions

Subarachnoid Hemorrhage

Diabetes Mellitus

A recent systematic review of the risk factors for subarachnoid hemorrhage (SAH) shows that smoking doubles the risk for SAH (Feigin et al., 2005). About one third of all SAH was found to be attributable to smoking in a smaller case-control study, and, although the risk dropped within a few years after quitting, it may remain increased for up to 15 years in the heaviest women smokers (Anderson et al., 2004). Older studies involving high-dose estrogen OCs showed a significant interaction with smoking, increasing the risk for stroke and SAH among women who both smoked and used OCs. Studies of women who use second and thirdgeneration OCs find no increased risk of stroke, even among smokers (Yang et al., 2009). However, the American College of Obstetricians and Gynecologists states that “practitioners should prescribe combination hormonal contraceptives with caution, if at all, to women older than 35 years who smoke” (ACOG, 2006).

Diabetes is a rapidly growing worldwide pandemic, and cigarette smoking is responsible for about 10% of the incidence of type 2 diabetes. A dose-response relationship exists, with the risk increasing in direct proportion to the number of cigarettes smoked. People who smoke more than one pack a day have about double the risk for diabetes as nonsmokers, and the risk is still 1.5 times greater for those who smoke only 1 to 14 cigarettes a day (Manson et al., 2000; Willi et al., 2007). Smoking increases the risk for development of the metabolic syndrome and its attendant cardiovascular consequences (Chiolero et al., 2008). Patients with diabetes who smoke are at increased risk for both micro- and macrovascular complications. Cigarette smoking increases the risk for diabetic nephropathy, retinopathy, and neuropathy. This association is strongest in patients requiring insulin for control. Smoking cessation is essential for preventing diabetic complications.

Peripheral Vascular Disease

Depression

Smoking is strongly associated with other forms of cardiovascular disease, including abdominal aortic aneurysm (AAA) and peripheral vascular disease in both men and women. Smoking causes as much as half of all peripheral artery disease, and significantly increases the failure rates after lower-limb bypass surgery. The risk of AAA rises in proportion to duration and intensity of smoking and is up to sevenfold greater at 20 pack-years (US Surgeon General, 2004). The U.S. Preventive Services Task Force (USPSTF) has recommended one-time screening for AAA by ultrasonography in men age 65 to 75 who have ever smoked. Consideration should also be given for screening women over age 65 with a history of smoking (Derubertis et al., 2007), because about 40% of the annual deaths from AAA occur among women, in whom the disease is more deadly than men. Smoking is also an independent risk factor for erectile dysfunction, an additional fact that may help motivate men to stop smoking.

Smokers are more likely to experience major depression than nonsmokers, and the incidence increases steadily with the number of cigarettes smoked. This increased risk may result from genes that predispose to both conditions (Kendler et al., 1993). Smoking may predispose to depression and, conversely, may be an antecedent to smoking, in the adolescent population (Brook et al., 2004; Goodman and Capitman, 2000).

1112

Alzheimer’s Disease Studies show conflicting evidence linking smoking with Alzheimer’s dementia and other causes of cognitive decline. However, a meta-analysis found that compared with neversmokers, current smokers had RRs of 1.79 for Alzheimer’s disease (AD) and 1.78 for vascular dementia. Smokers in this study also had greater yearly declines in Mini–Mental State Examination (Anstev et al., 2007). Another systematic review and meta-analysis also found significant risk for AD among smokers (RR, 1.59) but less risk for developing vascular dementia (1.35) and cognitive decline (1.20) compared with never-smokers (Peters et al., 2008).

Graves’ Disease Smoking appears to be one of the many factors causing Graves’ disease, particularly among women, and includes a higher risk of Graves’ ophthalmopathy as well (Vestergaard, 2002).

Wrinkles We are not very effective in getting the message about tobacco’s hazards across to adolescents. By talking about disease, we may not be speaking their language. The fact that smoking causes wrinkles, bad breath, and yellow teeth may be a more effective message than evidence that smoking kills. Premature wrinkling (crow’s feet) increases with the number of cigarettes smoked; heavy smokers are five times more likely to have wrinkles than nonsmokers (Kadunce et al., 1991).

Nicotine Addiction

Macular Degeneration and Cataract Macular degeneration is the leading cause of blindness after age 65, and nothing prevents or delays its progression. Smoking 20 or more cigarettes a day increases the risk of macular degeneration two- to threefold. As with other smoking-related disorders, macular degeneration also appears to be dose related, with the incidence increasing with the number of pack-years (Christen et al., 1996; Thornton et al., 2005). Smoking is also a cause of nuclear cataract, with smokers having two to three times the risk of never-smokers.

The Myth of Filtered Cigarettes There is a mistaken popular belief that filtered brands of cigarettes, which now account for more than 97% of those sold in the United States, are safer than nonfiltered cigarettes and that formerly labeled “light” cigarettes convey a degree of health protection. “Low-tar” and “low-nicotine” filtered cigarettes are now the most commonly purchased products. Because the addiction is to nicotine, people who smoke low-nicotine cigarettes undergo “compensatory smoking,” in which they inhale more frequently and more deeply to maintain their blood nicotine levels. As a result, tar intake increases, so the cigarette changes from the low-tar to the high-tar category. Smokers who take 14 puffs per cigarette inhale 58% more tar than those taking the standard 8.7 puffs per cigarette. Most manufacturers create tiny perforations in the filter to dilute the smoke with air, thus creating their “light” and “ultralight” cigarettes. Many smokers, however, block the holes with their lips or their fingers to obtain undiluted smoke with a higher concentration of nicotine (Kozlowski et al., 1980). Cigarettes with reduced yields of nicotine and CO are not safer. The fourfold increased risk of MI does not vary according to the nicotine content. The degree of risk is proportional to the number of cigarettes smoked (Palmer et al., 1989). Similar myths about “natural” and “organic” cigarettes should be dispelled, since there is absolutely no evidence that these tobacco products confer any health protection compared with other brands.

Cigars Key Points • C igars are not a safe alternative to cigarettes, causing both cancer and heart disease. • Cigar-related health risks are related to number smoked and depth of inhalation. • Risk of tobacco-related disease is increased when smoking is combined with alcohol consumption.

In 2004 the CDC estimated that about 9.4% of men, 1.9% of women, and 14.8% of students grades 8 to 12 were current cigar smokers. The mortality patterns from cigar smoking relate in part to the degree of inhalation by the smoker. Primary cigar smokers, or those who have never or rarely smoked cigarettes, inhale much less than secondary cigar smokers—those who have switched from or are concurrent cigarette smokers. The main reason for the difference is the

pH of the smoke, which in cigars is higher than in cigarettes, allowing nicotine to be absorbed across the oral mucosa. Secondary cigar smokers, however, have learned to inhale smoke, and increase their risk of cancer and heart disease. Cigar smokers have a risk of oral and pharyngeal cancer that is similar to cigarette smokers; their risk of esophageal cancer is several times that of never-smokers. As with cigarette smoking, the use of alcohol multiplies the risk of these cancers, accounting for about 75% of cases in developed nations (Pelucci et al., 2008). Lung cancer risk varies with depth of inhalation and number of cigars per day. Primary cigar smokers with no or slight inhalation have about a 1.8 mortality ratio of lung cancer; moderate-deep inhalers increase this to 4.9, with an overall mortality ratio of 2.11 compared with nonsmokers. Secondary cigar smokers have a mortality ratio of 5.4; moderate-deep inhalers in this group increase the risk to 9.77. Combined cigarette-cigar smokers have an overall lung cancer mortality ratio of 11.20 (NCI, 1998). Cigar smokers are also at higher risk for both COPD (RR, 1.45) and coronary artery disease (RR, 1.27) compared with nonsmokers (Iribarren et al., 1999). As with the cancer risk, the level of inhalation increases risk; for example, secondary cigar smokers with moderate-deep inhalation patterns have a fivefold increased risk for COPD (NCI, 1998).

Electronic Cigarettes Electronic cigarettes (e-cigarettes), first developed in China in 2003, consist of a metal tube resembling a normal cigarette, a battery, an atomizer, and a replaceable cartridge containing liquid nicotine, propylene glycol, and flavoring. Examples of flavorings are chocolate, cherry, and bubblegum, all of which can be enticing to children. When a user puffs on the e-cigarette, an indicator light at the tip glows and the heating element vaporizes the solution from the cartridge containing nicotine and other substances. A mist is produced that is similar to cigarette smoke and contains the propylene glycol, a known pulmonary irritant used in antifreeze. To date there are no published clinical trials and there is no quality control to limit the amounts of chemicals in e-cigarettes, including known carcinogens. The sale of electronic cigarettes containing nicotine is illegal in Australia. In the United States the American Cancer Society (ACS) and other professional organizations have called for e-cigarettes to be illegal. The U.S. Food and Drug Administration (FDA) has not approved these devices and has halted shipments of them from entering the country, but Internet sales are growing. In 2009 the U.S. Congress granted the FDA the power to regulate tobacco products, including the authority to stop e-cigarettes from entering the country. Electronic cigarettes, even though smokeless, may contain known carcinogens and toxic chemicals. There is considerable debate as to whether these products might deliver nicotine with minimal additional harm to the smoker, becoming a “harm reduction” instrument that enables smokers to continue their nicotine dependence and reduce risk or enhance quit attempts. On the other hand, these products have little quality control; nicotine delivery is inconsistent; FDA-type testing has not yet been done; and longterm risks are not known. 1113

50

Nicotine Addiction

Smokeless Tobacco Key Points • S nuff users have a 50-fold increased risk of cancer of the cheek and gum. • The carcinogens in smokeless tobacco have a greater concentration than in cigarette tobacco; the level of nitrosamines is more than 10,000 times that allowed in bacon and beer.

Smokeless tobacco comes in two types: snuff, which is dry or moist, and chewing (spitting) tobacco, which comes as a loose leaf, plug, or twist. Smokeless tobacco contains many of the same carcinogens as cigarette tobacco, but some are present in much greater concentrations. Nitrosamines, which are powerful chemical carcinogens, are present at levels up to 14,000 times higher than the federal government allows in bacon and beer (Connolly et al., 1986). A variation on smokeless tobacco is called snus, which contains powdered, flavored tobacco in small satchets placed under the lip, releasing nicotine through the buccal mucosa. Because of differences in manufacturing, snus has comparatively small levels of the carcinogenic compounds found in traditional smokeless products. No spitting is required. Snus marketing campaigns emphasize its use when smoking is not allowed, and most U.S. snus users also smoke cigarettes. In Sweden, snus use has eclipsed smoking, and many smokers have used snus to quit smoking but have continued using snus, and many appear to be dependent. Again, in the United States, this has sparked a fierce debate about the use of snus and similar products as agents for “harm reduction,” and whether smokers should be advised to switch as a means of smoking cessation, since exclusive smokeless tobacco use avoids many of the dangers of combustible tobacco. Treatment of smokeless tobacco use is difficult, because none of the standard medications used for smoking cessation has shown effectiveness for smokeless tobacco users, although behavioral counseling has a modest effect (Fiore et al., 2008). The nicotine patch and lozenge have been suggested, and clinical trials of combination therapy are ongoing. Behavioral interventions such as mailings, oral or dental screenings, group discussions, workplace interventions, and telephone support showed the best evidence for smokeless tobacco cessation (SOR: B). There was no benefit from the use of bupropion SR or nicotine patches or gum (Cayley, 2009; SOR: A). Use of smokeless tobacco increases the frequency of oropharyngeal cancer and causes gum recession and tooth loss. Overall, the RR for oral cancer among snuff users is 2.6; for esophageal and pancreatic cancer, 1.6 (Boffetta et al., 2008). Leukoplakia is found in 18% to 64% of users (Connolly et al., 1986). Snus has been associated with a higher risk of oropharyngeal cancer in some studies (Roosar et al., 2008), but not others (Luo et al., 2007), and also has a small risk of pancreatic cancer. A systematic review and meta-analysis of the risk for myocardial infarction and stroke among current smokeless tobacco users found small increases in relative risk for these conditions (Boffetta and Straif, 2009). Although educational programs have been launched by the National Cancer Institute and Major League Baseball, smokeless tobacco use has trended upward in adolescents. College athletes often believe that male peers, coaches, and 1114

professional athletes are indifferent to the use of spitting tobacco (Hilton et al., 1994). An estimated 8.6% of high school students are current smokeless tobacco users. Smokeless tobacco is more common among high school boys (14%) than girls (2.2%). As with college students, many high school spit tobacco users participate in organized sports. Enlisting the support of coaches to help with tobacco use prevention is an untapped resource that should be explored.

Involuntary (Passive) Smoking Key Points • S econdhand smoke contains 4000 different chemicals, of which more than 60 are carcinogenic. • About one third of lung cancers occur in nonsmokers who live with a smoker or work in a smoky environment. • Passive smoking is the third leading preventable cause of death, after alcohol and smoking itself. • Passive smoking increases the risk of SIDS in infants and otitis media, cancer, and respiratory disease in older children, in direct proportion to smoke exposure.

Secondhand smoke, also called environmental tobacco smoke (ETS), is the combination of smoke emitted from the burning end of a cigarette, cigar, or pipe and the smoke exhaled by a smoker. Two thirds of the smoke from a burning cigarette never reaches a smoker’s lungs, but instead goes directly into the air. Sidestream smoke is emitted into the air from a smoldering cigarette or cigar between puffs, and mainstream smoke is what the smoker inhales directly—the exhaled smoke also contributes to ETS. Although diluted by air before being inhaled, sidestream smoke contains greater concentrations of toxic substances than mainstream smoke because of a lower combustion temperature and lack of filtration through the cigarette. The 2006 Report of the Surgeon General, The Health Consequences of Involuntary Exposure to Tobacco Smoke (USHHS, 2006), concludes the following: 1. Secondhand smoke causes premature death and disease in children and adults who do not smoke. 2. Children exposed to secondhand smoke are at increased risk for sudden infant death syndrome (SIDS), acute respiratory infections, ear problems, and more severe asthma. Smoking by parents causes respiratory symptoms and slows lung growth in their children. 3. Exposure of adults to secondhand smoke has immediate adverse effects on the cardiovascular system and causes coronary heart disease and lung cancer. 4. The scientific evidence indicates that there is no risk-free level of exposure to secondhand smoke. 5. Eliminating smoking in indoor spaces fully protects nonsmokers from exposure to secondhand smoke. Separating smokers from nonsmokers, cleaning the air, and ventilating buildings cannot eliminate exposures of nonsmokers to secondhand smoke. Tobacco smoke contains more than 4000 different chemicals, at least 60 of which are known carcinogens (National Toxicology Program, 2005). The U.S. Environmental Protection Agency, (EPA) the National Toxicology Program, the U.S. Surgeon General, and the International Agency for Research on Cancer have determined that environmental

Nicotine Addiction

tobacco smoke is a class A (known) human carcinogen, in the same class as asbestos, mustard gas, arsenic, and benzene. In addition to the 3000 lung cancer deaths a year in nonsmokers, almost 40,000 heart disease deaths each year are linked to secondhand smoke. Secondhand smoke exposure also causes chronic otitis media, cough, and lower respiratory illnesses in children, such as asthma, bronchitis, and pneumonia. It is estimated that tobacco smoke in the home and workplace could be responsible for the deaths of about 50,000 nonsmokers annually in the United States, making passive smoking the third leading preventable cause of death, after those from direct smoking and alcohol (Air Resources Board, 2005). In a classic study, Hirayama (1981) was among the first scientists to demonstrate an increased risk of lung cancer in nonsmoking housewives exposed to the secondhand cigarette smoke of their husbands (see eFig. 50-2 online). Since then, many studies have shown an association between being married to a smoker and having an increased risk of lung cancer. Overall risk of lung cancer increases 20% to 30% in nonsmokers exposed to ETS in the home; combined home and work exposure further increases the risk (USDHHS [Report of the Surgeon General], 2006). A report from the California EPA’s Air Resources Board is another well-researched review of the health effects of passive smoking. Their meta-analyses of the breast cancer risk indicate that the RR for breast cancer, particularly among premenopausal women, is between 1.68 and 2.20 (Air Resources Board, 2005; Miller et al., 2006). A 2009 Canadian task force report found a causal link between passive smoke exposure and breast cancer, especially in younger, premenopausal women, and a causal relationship between active smoking and breast cancer at all ages (Johnson et al., 2011). It is estimated that the risk of MI is up to 70% greater for a woman whose husband smokes (Wells, 1994). Relative risk estimates from meta-analysis indicate a 25% to 30% increase in the risk for coronary heart disease in exposed nonsmokers; as with lung cancer, multiple sites of exposure increase the risk (USDHHS [Report of the Surgeon General], 2006). The cardiovascular effects of even brief exposure to secondhand smoke are often nearly as great as those of direct smoking, with platelet aggregation and arterial endothelial damage occurring within 30 minutes of exposure; furthermore, secondhand smoke induces oxidative stress and promotes vascular inflammation (Barnoya and Glantz, 2005). Exposure to secondhand smoke is associated with increased levels of inflammatory markers related to the development of atherosclerosis. People exposed have higher white blood cell counts and elevated CRP levels, oxidized LDL cholesterol, homocysteine, and fibrinogen. Even occasional exposure results in elevated levels. These increases are similar to those seen in active smokers. Reports show that the health benefits of banning smoking in public places and the workplace include a reduction in heart attacks. Examination of community MI rates after implementation of strong smoke-free legislation found a pooled random-effects estimate of the rate of acute MI hospitalization 12 months later to be 0.83 (95% CI, 0.80-0.87), with growth of this benefit expected over time (Lightwood and Glantz, 2009). With similar findings, systematic review and meta-analysis of 10 locations with smoke-free legislation concluded that the acute MI risk decreased by 17% overall,

with the greatest effect in younger individuals and nonsmokers (Meyers et al., 2009).

Secondhand Smoke: Effects on Children Over 50% of children younger than 5 years of age live in homes with at least one adult smoker. Children of smoking parents have more bronchitis and pneumonia during their first year of life and more otitis media when older. They have increased incidence of cough, bronchitis, and pneumonia proportional to the number of cigarettes smoked by the parents, particularly the mother. In fact, children of parents who smoke at least a half-pack a day have almost twice the risk of hospitalization for a respiratory illness. Secondhand smoke causes new-onset asthma in exposed children, and young persons with asthma have more asthma episodes (Charlton, 1994; Rantakallio, 1978; USHHS [Report of the Surgeon General], 2006). Passive smoking also increases the risk of sudden infant death syndrome. Infants exposed to secondhand smoke have twice the risk of SIDS, and infants whose mothers smoke before and after birth are three to four times more likely to die from SIDS (US Surgeon General, 2004, 2006). Small children are victimized more by passive smoking than adults. Because of their more rapid breathing, children inhale larger amounts of harmful substances. Children exposed to their parents’ cigarette smoke have six times the average number of respiratory infections. They also have deficits in growth and in intellectual and emotional development, as well as more behavior disorders, such as hyperactivity. Physicians and health care providers who care for children should advise parents to quit smoking to limit their children’s exposure to secondhand smoke, and advocate for smoke-free indoor air both at home and in cars when children are passengers, since these two locations account for the majority of childhood exposure to secondhand smoke.

Thirdhand Smoke Thirdhand smoke occurs when cigarette smoke reacts with nitrous acid on surfaces to form tobacco-specific nitrosamines (TSNAs). Nitrous acid is a common indoor pollutant and, when combined with cigarette smoke, forms a carcinogen that becomes more potent over time. Thus, nicotine is converted to a dangerous carcinogen after it is absorbed on indoor surfaces in automobiles and furniture. This can be especially hazardous to infants and children who live close to the floor because the TSNAs are especially concentrated in dust and carpeting. Smokers believed that smoking only when others were not present (e.g., in car or home) created no risk to the nonsmoker who arrives later. In fact, the smoke clings to upholstery, cotton, and carpeting and actually builds up over time, exposing the nonsmoker to potent carcinogens. This thirdhand smoke can be especially dangerous because TSNAs cannot be simply inactivated by dry cleaning or washing with soap and water. Most soaps are alkaline and cleansers that dissolve nicotine must be acidic. Thus, it is almost impossible to remove TSNAs from carpeting, which will continuously uptake nicotine. Even washing smooth stone and metal with an alkaline soap will not remove nicotine residue (Dreyfuss, 2010; Sleiman et al., 2010). 1115

50

Nicotine Addiction

Pregnancy See the discussion online at www.expertconsult.com.

Key Points • T he more a pregnant woman smokes, the greater the risk of premature delivery and low-birth-weight infants, unless she stops smoking by the fourth month of gestation. • Smoking during pregnancy increases the risk of congenital abnormalities, mental retardation, learning problems, and attention-deficit/hyperactivity disorder (ADHD). • The risk is increased for spontaneous abortion, placenta previa, and premature rupture of membranes. • Reduced fertility is proportional to the number of cigarettes smoked.

KEY TREATMENT Because of the serious risks of smoking to the pregnant smoker and the fetus, whenever possible pregnant smokers should be offered person-to-person psychosocial interventions that exceed minimal advice to quit (Fiore et al., 2008) (SOR: A). Although abstinence early in pregnancy will produce the greatest benefits to the fetus and expectant mother, quitting at any point in pregnancy can yield benefits. Therefore, physicians should offer effective tobacco-dependence interventions to pregnant smokers at the first prenatal visit and throughout pregnancy (Fiore et al., 2008) (SOR: B).

Smoking and Mental Health Mental illness and substance abuse puts patients at particular risk for dying of tobacco-related illness because they are more likely to smoke, and smoke more heavily, than others in the population. Patients with psychiatric illness consume up to70% of the cigarettes smoked in the United States, with two to four times the general prevalence of smoking (Grant et al., 2004; Kalman et al., 2005). Among mentally ill and substance-abusing patients, as many as 200,000 die each year from tobacco-related causes—almost half the total U.S. tobacco-related mortality (Williams et al., 2004). Individuals in this special population of smokers do express strong interest in quitting smoking, however. Counseling and pharmacology that is useful with other smokers is effective in mentally ill and substance-abusing patients who smoke (Ranney et al., 2006), and just as with other smokers, this part of their health care must not be neglected.

Social and Legal Action See online text for discussion.

Smoking Cessation Key Points • P atients who smoke should receive advice and encouragement to stop at every visit. • Take advantage of the teachable moment, when a patient who smokes is being treated for any medical condition. 1116

• M ultiple strategies and persistence are usually needed for successful cessation because tobacco dependence is a chronic disease. • Brief counseling, usually lasting less than 3 minutes, is an effective way to begin intervention.

Family physicians are in a unique position to assist their patients in smoking cessation. Because 7 of every 10 smokers visit their physician at least once a year, this is a golden opportunity that should not be missed. Among smokers, 70% want to quit and about 40% make an attempt each year, but less than 5% succeed. Even brief physician advice can double the quit rate (Fiore et al., 2008). Of those who try to quit on their own and do not use recommended cessation methods, most relapse within 8 days (CDC, 2008). A survey by the Association of American Medical Colleges (AAMC, 2007) about physician behavior related to smoking cessation is summarized as follows: Most physicians consistently ask patients who smoke about their smoking status and advise them to stop (86%), but only 13% say they usually refer smokers to others for appropriate treatment and only 17% say they usually arrange for follow-up visits to address smoking. Only 31% “usually” advised use of nicotine replacement therapy, and 25% “usually” prescribed other medication for cessation. Only 7% regularly referred patients to a quit line. Physicians regard current smoking cessation tools as inadequate, citing the following: • Insufficient services, resources, and organizational support • Interventions that have only limited effectiveness • Limited education and training for physicians on addressing tobacco use and cessation interventions The five factors cited most often by physicians as significant barriers to successful interventions are lack of patient motivation (63%), limited coverage for interventions (54%), limited reimbursement for a physician’s time (52%), time with patients is limited (41%), and too few available cessation programs (39%). Patients should be asked about tobacco use at every visit because repeated screening increases rates of clinical intervention. Tobacco users should be advised to quit at every visit (SOR A), because there is a dose-response relationship between the number of contacts and abstinence. Tobacco use screening coupled with brief advice is one of the topthree clinical prevention measures and is cost-effective as well (Maciosek et al., 2006). Tobacco-cessation treatment may include a variety of components: counseling for behavior change in both individual and group settings, such as motivational interviewing and problem solving/skills training; use of evidence-based pharmacotherapy; and proactive telephone quit line counseling (Fiore et al., 2008; USPSTF, 2009). Patients should receive at least minimal advice and encouragement at every visit based on the five “As” approach (Box 50-2). The American Academy of Family Physicians (2005) has a campaign to encourage its members to engage themselves in smoking cessation interventions. Using two As, “Ask and Act,” the AAFP program emphasizes brief counseling and effective follow-up.

Nicotine Addiction

Box 50-2 Five As for Tobacco Users Willing to Quit Ask about tobacco use at every visit. Advise to quit through clear personalized messages. Assess willingness to quit. Assist efforts to quit. Arrange follow-up and support.

As part of taking the history from a patient who smokes, clinicians should ask the following three questions to assess the patient’s degree of nicotine addiction: 1. How much do you smoke? (How many cigarettes or cans of “dip” per day, for how many years?) 2. When do you smoke the first cigarette of the day? 3. How long is the period between cigarettes before craving another smoke? Patients who smoke more than 20 cigarettes a day, who light their first cigarette within 30 minutes of waking, and who have cravings within 1 hour of the most recent cigarette are likely to have significant physiologic addiction to nicotine. Smoking fewer than 10 cigarettes a day suggests less addictive behavior, and a few patients report that they smoke only during social situations and only 5 to 10 cigarettes a week. Determining the patient’s pattern of smoking will provide clues into the level of addiction. Office spirometry to obtain a forced expiratory volume in 1 second (FEV1) can also be useful in motivating smokers to quit. Comparing the smoker’s “lung age” to the age of a healthy individual who has the same FEV1, then showing the smoker a graphic display (Fig. 50-5, A), more than doubled the rate of quitting smoking after 12 months (13.6% vs. 6.4%) (Parkes et al., 2008). For example, a 52-year-old smoker with a 20-pack-year history (1 pack/day for 20 years) may have the lung age of a 75-year-old. Probable age at disability and death if the person continues smoking or stops smoking can be shown (Fig. 50-5, B). Such a visual presentation is often effective in achieving cessation even if smokers have a normal lung age because they may think it is not too late for them to quit.

Stages of Change Patients who begin any major behavioral or lifestyle change go through successive stages in the process, as follows: Precontemplation: Patient is not interested in quitting smoking in the near future (within 6 months). Contemplation: Patient is thinking about quitting within the next few months, but has taken no action. Preparation: Patient is planning to quit in the next 30 days. Action: Patient is in the process of quitting, or has quit during the last 6 months. Maintenance: Patient has abstained for more than 3 months. Family physicians should emphasize progression through the process of change to facilitate the patient’s efforts to stop smoking. When a patient reaches the preparation stage, the physician can play a major role in motivating the patient, including counseling and routine use of pharmacotherapy. However, recent research indicates that many smokers do not go through sequential stages and are often successful in quitting during spontaneous, unplanned attempts, perhaps sparked by an illness or by policy changes such as price increases or clean indoor air laws. Physicians’ continued

s upport and encouragement may help increase the frequency and success of these efforts (Ferguson et al., 2009).

Helping to Change Behavior In addition to the support for smoking cessation activity described by the U.S. Public Health Service (Fiore et al., 2008), motivational interviewing is a patient-focused approach to discussing patients’ ambivalence about changing their tobacco use behavior. Motivational interviewing uses empathy and a nonjudgmental style to open a dialogue that can show the importance of change and build a patient’s self-motivation. Patients can build on prior success (even brief) and become more active partners in the path to abstinence (Mallin, 2002; Miller and Rollnick, 2002). A clear relationship exists between the intensity of counseling and its effectiveness. Although even brief counseling (≤3 minutes) doubles the spontaneous quit rate, intensive therapy can be more effective and should be used whenever possible (Fiore et al., 2008). Both physicians and their patients who smoke should think of nicotine dependence as a chronic disease, usually characterized by many episodes of remission and relapse. A number of strategies are often needed, and expectations must be realistic, because smokers usually do not succeed on their first or even second attempt. Clearly, however, the chances of success increase with each attempt, and relapse should not be considered a sign of failure. Intensive counseling is associated with a 22% smoking-cessation success rate and even minimal counseling (300 enzymatic reactions One third of supply is on bone surfaces Involved in cyclic adenomonophosphate formation, nerve transmission, neuromuscular junction transmission Serum level poorly correlated with body stores Regulated by parathyroid hormone No research supporting claims of optimal calcium/magnesium ratio

ADHD Altitude sickness Allergies, asthma Cardiovascular disease Cerebral edema CHF Chronic fatigue Constipation (A) COPD Diabetes, insulin resistance Dyslipidemia Fibromyalgia GERD (A) Hearing protection Hypomagnesemia (A) Incontinence Leg cramps in pregnancy Lipid abnormalities Migraines Multiple sclerosis Osteoporosis PMS Preeclampsia (A) Renal calculi Restless legs Skin disorders (topical) Stroke Tetanus Torsades de pointes (A) Vasospastic angina

Upper intake level: 350 mg/day (often used at higher doses). Diarrhea, thirst, hypotension, fatigue, reflex loss. Two case reports of death. Can cause weakness, arrhythmias, and coma at high doses Deficiency linked to increase substance P and osteoclast activity Levels lower in women with PMS, diabetics, elderly, alcoholics, patients with malabsorption and renal disease Levels decreased by boron, calcium, zinc, amphotericin, beta-2 agonists, cisplatin, cholestyramine, corticosteroids, cyclosporine, digoxin, loop diuretics, quinolones, foscarnet, penicillamine, pentamidine, phosphates (Fleet enemas), tetracyclines Used with aminoglycosides can lead to neuromuscular weakness and paralysis Decreases absorption of quinolones, tetracyclines Levels increased by vitamin D, potassium-sparing diuretics, estrogens Decreases bisphosphonate absorption May have additive effects with calcium channel blockers at high doses May enhance effects of muscle relaxants Mg glycenate results in less diarrhea Caution with supplementation in patients with renal failure

Manganese (Mn) Cofactor in several enzymatic reactions

Deficiency states (A) Microcytic anemia Osteoarthritis (usually in combination products) Osteoporosis PMS

Neurotoxicity possible in patients with liver disease Calcium and iron can decrease absorption Zinc can increase levels May decrease quinolone and tetracycline levels

Selenium (Se) Antioxidant: activates glutathione peroxidase Promotes T-helper cell growth, development Selenomethionine incorporated into proteins and serves as storage mechanism Food levels depend on food-soil content

Abnormal Pap smears Atherosclerosis Allergic rhinitis Cancer prevention Gray hair HIV/AIDS Heart disease Infertility Low thyroid Miscarriage prevention Mood disorders Osteoarthritis Rheumatoid arthritis

Upper intake level: 400 μg daily Toxicity if >910 μg daily: nausea, vomiting, nail changes, fatigue, irritability, weight loss, thrombocytopenia, hepatorenal dysfunction Can inhibit vitamin C absorption. Pregnancy: iron decreases Se accumulation Taken with other supplements, seems to decrease statin and niacin effectiveness May decrease male fertility and increase skin cancer risk at high doses

Silver (colloidal) No known physiological function, despite marketing claims

Cancer prevention Chronic fatigue Chronic lung disease Improve digestion Infections (everything from ears and sinuses to TB and plague)

Argyria (blue-gray skin discoloration) possible with long-term use May decrease absorption of thyroid medications, penicillamine, quinolones, tetracyclines

Continued

e19

52

Herbs and Other Dietary Supplements

Table 52-5 Vitamin and Mineral Supplements*—cont’d

Name

Indications/Evidence

Effects/Interactions/Comments

Vanadium (V) Used in bone growth, inhibits ATPases and other phosphorus transfer enzymes May mimic insulin actions on receptors

Athletic performance Diabetes (esp. type 2) Edema Cardiovascular disease Hypoglycemia Hyperlipidemia TB, syphilis

Pentoxide form highly toxic Significant GI effects Can augment effects of hypoglycemic drugs May increase anticoagulant effects Avoid in patients with renal disorders

Zinc (Zn) Cofactor in DNA, RNA, protein synthesis Part of >300 enzymes, catalyst for ~100 others Tied to neutrophil, T-lymphocyte, and natural killer cell function May influence cellular glucose transport

ADHD Alzheimer’s disease Anorexia nervosa Aphthous ulcers Athletic performance BPH Burns (zinc oxide) Deficiency (A) Eye disorders Hypogeusia IBD Immune booster Infections: treatment, prevention Male impotence, infertility Osteoporosis Skin problems Rheumatoid arthritis Tinnitus URI prevention Wilson’s disease (A)

Upper intake level: 40 mg/day Can cause GI effects and metallic taste Can lead to copper deficiency Overdose: nervous system symptoms, severe GI distress, decreased immune function, renal tubular necrosis, interstitial nephritis Too much may reduce magnesium levels Case reports of anosmia with zinc gluconate nasal gel Levels increase with amiloride Levels decreased in malabsorption syndromes, rheumatoid arthritis, and patients taking penicillamine, thiazide and other diuretics, and ACE inhibitors May increase toxicity of cisplatin Decreases absorption of quinolones, tetracyclines May be a link to higher zinc intake and lowered survival time in patients with HIV infection

Data from Basch EM, Ulbricht CE. Natural Standard Herb and Supplement Handbook: The Clinical Bottom Line. Boston, Elsevier-Mosby, 2005; Mahan LK, Escott-Stump S (eds). Krause’s Food Nutrition and Diet Therapy, 11th ed. Philadelphia, Saunders-Elsevier, 2004; and Natural Medicines Comprehensive Database (accessed November 2009). *Many of the vitamins and minerals listed are used for dozens of different indications; only the most common (and when possible, most researched) indications are listed. Lack of randomized controlled trial (RCT) research is not equivalent to lack of efficacy. An “A” in parentheses after a supplement name denotes an A rating according to the Strength of Recommendation Taxonomy (SORT). The rating is based on systematic review data summarized primarily in the references by Basch and/or Natural Medicines Comprehensive Database (NMCD). A classification of “A” is assigned if the supplement was rated as one of the following: (1) evidence grade A or B in Basch (indicating strong or good evidence of effect) or (2) rating of “Effective” or “Likely effective” in NMCD, suggesting the same. Not all supplement monographs reach the same conclusions regarding the evidence base for particular supplements. Indications followed by a “(−)” have been rated category D by Basch (indicating “Fair negative scientific evidence”) or as “Likely ineffective” by NMCD. Adverse effects or interactions preceded by “May” are speculative. No case reports or trials have verified their existence. ACE, Angiotensin-converting enzyme; AIDS, acquired immunodeficiency syndrome; ADHD, attention-deficit hyperactivity disorder; ATP, adenosine triphosphate; BPH, benign prostatic hypertrophy; CAD, coronary artery disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CSF, cerebrospinal fluid; DNA, deoxyribonucleic acid; GABA, γ-aminobutyric acid; GERD, gastroesophageal reflux disease; GI, gastrointestinal; H2, histamine 2, H. pylori, Helicobacter pylori; HIV, human immunodeficiency virus; IBD, inflammatory bowel disease; IM, intramuscular; IU, international units, MI, myocardial infarction; NSAIDs, nonsteroidal anti-inflammatory drugs; PIH, pregnancy-induced hypertension; PMS, premenstrual syndrome; PPIs, proton pump inhibitors, RDA, recommended daily allowance; RNA, ribonucleic acid; TB, tuberculosis; URI, upper respiratory infection.

e20


Table 52-6 Common Nutraceuticals*

Name and Description

Uses/Efficacy

Effects/ Drug Interactions

Alpha-lipoic acid Coenzyme involved in the production of adenosine triphosphate Antioxidant

Diabetes (type 2) HIV dementia Liver disease Neuroprotective Peripheral neuropathy

Inhibits HIV reverse transcriptase in vitro Temporary worsening of paresthesias at beginning of therapy Most adverse effects are when given IV May lower blood sugars when used with diabetes drugs May be more toxic in thiamine deficiency

Acetyl-l-carnitine Exists in the body as part of “carnitine pool” Involved in mitochondrial function Involved in transport of long-chain fatty acids

Cognitive impairment Dementias Male infertility Peripheral neuropathies Peyronie’s disease Testosterone deficiency

May cause GI irritation or agitation Increases sperm motility Increases effects of anticoagulants May reverse zidovudine inhibition of carnitine transport into muscle Deficiency may be caused by taking carbamazepine, phenobarbital, phenytoin, or valproic acid May increase seizures, as reported with l-carnitine May inhibit activity of thyroid hormone; caution in hypothyroidism

Antioxidants Compounds that scavenge for free radical electrons in body or prevent formation Vitamins A, C, E; green tea components; selenium; grape seed extract

Cancer prevention and treatment Chronic disease prevention Heart disease prevention

May counteract the effects of various chemotherapeutic and immune-suppression agents (no data for this) Unclear whether or not antioxidant supplements as effective as combinations found in foods

Arginine “Semi-essential” amino acid Nitric oxide precursor (vasodilation)

Burn recovery Claudication CAD (−) Erectile dysfunction (benefit in one trial) Ibuprofen arginate for pain control Infertility Interstitial cystitis

Worsens inflammation in asthma Follow potassium levels with diuretic and ACE inhibitor use May raise blood sugar May increase bleeding risk with anticoagulant/antiplatelet drugs

Bioflavonoids Plant pigments (provide yellow, red, and orange coloration) Antioxidants Iron chelators See also Quercetin

Diosmin: hemorrhoids Hesperidin: hemorrhoids and venous stasis ulcers Methoxylated bioflavones: cancer prevention Rutin: vascular disorders (e.g., venous stasis, insufficiency); osteoarthritis; stroke prevention

Few known drug interactions or adverse effects Methoxylated bioflavones may induce CYP1A2, decreasing levels of fluvoxamine, beta blockers, olanzapine, zolmitriptan, imipramine, cyclobenzaprine, other medications

Choline Often classed as a “B vitamin,” but synthesized by body Precursor of acetylcholine (ACh), but no evidence choline affects brain levels of ACh when supplemented Component of phosphatidylcholine, a component of lecithin

Asthma Age-related cognitive impairment (−) Cerebellar ataxia Depression Huntington’s chorea Liver disease (A for TPN hepatic steatosis) Neural tube defect prevention Performance enhancement Schizophrenia (−) Tourette’s syndrome

Can cause GI distress, diaphoresis, and fishy body odor No drug interactions known

Chondroitin Component of cartilage, synthesized or extracted from bovine or shark cartilage

Osteoarthritis (A)

Well tolerated Caution in bleeding disorders or with anticoagulants Structurally similar to heparin; avoid in pregnancy

Coenzyme Q10 Essential for cellular function, part of electron transport chain in mitochondria Levels decrease with age

Alzheimer’s disease Angina Athlete performance (−) Cardiomyopathy CHF Gum disease (−) Hypertension (A) Medication-induced cardiac damage Mitochondrial encephalomyelopathy (A) Muscular dystrophy Parkinson’s disease Post-MI

Few side effects May decrease blood sugar levels May affect platelet levels (one case report) Rare liver function test and thyroid hormone elevations May reduce effects of anticoagulants (theoretic) Many drugs seem to lower natural levels in the body, including some antipsychotics, beta blockers, sulfonylureas, metformin, some statins, some TCAs

e21

52


Table 52-6 Common Nutraceuticals*—cont’d


Uses/Efficacy


Creatine Synthesized in liver and kidney and liver from amino acids Most adults receive 1-2 g daily in diet

Athlete conditioning (−) CHF Muscular dystrophy Exercise in short bursts made easier Lipid disorders

Used heavily by adolescents above recommended doses Can trigger allergic symptoms May cause muscle cramping, breakdown Link to dehydration, heat intolerance Avoid in renal and liver disease Case report of increased risk of compartment syndrome Probenecid may increase levels May alter blood glucose levels Caution with diuretic use (electrolyte abnormalities) May augment effects of anti-inflammatory drugs

Dehydroepiandrosterone (DHEA) Endogenous adrenal hormone Levels decrease after age 30 Levels decrease with anorexia, type 2 diabetes, and other chronic illnesses

Adrenal insufficiency Atherosclerosis Athletic performance Cervical dysplasia Chronic fatigue Crohn’s disease Dementia (−) Depression Heart failure HIV Immune booster (−) Lupus Menopause symptoms Mental performance (−) Osteoporosis Ovulation disorders Schizophrenia Sexual performance

May be depleted by insulin, steroids, opiates, danazol Can raise androgen and estrogen levels, possibly increasing risk of hormone-sensitive cancers Adverse events such as palpitations rare Risk of masculinization, increased blood pressure, aggression Monitor thyroid, cholesterol, glucose May alter CYP metabolism May increase coagulation Levels may be increased by calcium channel blockers and alprazolam May contribute to tamoxifen resistance in breast cancer May decrease methadone’s effects

Ethylenediamine-tetraacetic acid (EDTA) Clawlike molecular structure; binds divalent and trivalent ions

Atherosclerosis Cardiac glycoside heart toxicities (A) Chelating agent (used IV to reduce oxidation; no evidence of benefit) Heavy metal poisoning (A) Hypercalcemia (A) Metal-induced skin rash

Nephrotoxicity in excessive oral doses IV: GI distress, hypotension, dermatitis, pain at infusion site, flulike symptoms, arrhythmias, anemia, urinary urgency May decrease anticoagulant effects Severely decreases serum glucose when taken by insulin users Can decrease potassium levels (caution with diuretics)

Fructo-oligosaccharides Plant sugars that occur in plant-based foods-(e.g., inulin)

Colon cancer prevention Constipation Inulin used for elevated triglycerides Prebiotic: used to promote growth of healthy intestinal flora

May cause GI discomfort Maintaining healthy gut flora may decrease symptoms of irritable and inflammatory bowel disorders

γ-Hydroxybutyrate (GHB) Occurs naturally in brain, especially basal ganglia, as well as kidneys, liver, muscle, and brown fat Metabolite of GABA Induces REM sleep FDA removed from market in 1990, but still widely available Schedule III substance

Alcohol dependence and withdrawal Fibromyalgia sleep disturbance Muscle growth Narcolepsy (FDA approved) Posthypoxic cerebral edema Sexual performance Weight loss

GHB and related compounds linked to 122 reports of serious adverse reactions, including bradypnea and death High doses can cause amnesia and decreased muscle tone Two reports of death, taken with alcohol Can cause dependence Potentiated by benzodiazepines May be antagonized by antipsychotics Near-fatal reactions with ritonavir and saquinavir reported “Date rape” substance

Glucosamine Normal constituent of cartilage matrix

Inflammatory bowel disease TMJ disorders Osteoarthritis (A) Venous insufficiency

Well tolerated; rare palpitations May increase cataract risk Proteinuria in several patients (unclear significance) May worsen asthma symptoms May alter drug effects on glucose levels May have more side effects when taken with diuretics

e22




Uses/Efficacy


Glutamine Most abundant free amino acid in body, made in skeletal muscle Can enhance immune cell function Levels reduced in some cancer patients

Crohn’s disease HIV-related wasting Mood disorders Mucositis from chemotherapy Other chemotherapy side effects Posttrauma nutrition

Minimal side effects Theoretic increases in tumor growth have not been found to occur May antagonize some antiepileptics May antagonize antiammonia effects of lactulose Avoid if sensitive to monosodium glutamate (MSG)

5-Hydroxytryptophan (5-HTP) Created from l-tryptophan and converted into serotonin in body

ADHD Anxiety Depression Fibromyalgia Headache Premenstrual syndrome Sleep disorders

Safety controversial May be link to eosinophilia-myalgia syndrome for some products May increase serotonergic and adverse effects of SSRIs and carbidopa, dextromethorphan, meperidine, tramadol

Inositol hexaphosphate (IP-6) Major phosphorus storage compound in plants; 1%-7% of weight of most cereals, nuts, and legumes Reduces formation of calcium, oxalate crystals

Antioxidant CAD prevention Cancer treatment and prevention Immune system enhancement Renal calculi

May increase anticoagulant effects (not demonstrated in humans) May decrease mineral absorption (e.g., calcium, iron, zinc) No adverse reactions reported

Lutein Accounts for 11% of carotenoids in serum and 22% in adipose tissue Antioxidant Thought to filter harmful blue-spectrum light

Cataracts Cancer prevention (colon) Macular degeneration

Most benefits found in epidemiologic studies; benefits of supplementation unclear Beta-carotene may reduce lutein bioavailability Dose is 6-10 mg/day for eye benefit in studies; many products contain much less

Lycopene Carotenoid found in serum, liver, adrenals, prostate, colon, skin, lungs at relatively high levels Derived from tomatoes

Antioxidant Asthma Atherosclerosis Cancer prevention Macular degeneration

Unclear if benefits found for diets high in fruits and vegetables apply for supplementation Limited studies of adverse effects May contribute to increased gastric acidity

Melatonin Neurohormone produced in pineal gland from tryptophan Has antioxidant activity

ADHD Benzodiazepine tapering Cancer, HIV, other chronic illnesses Cluster headache Delayed sleep phase syndrome (A) Depression (−) Glaucoma Insomnia in elderly (A) Jet lag (A) Mood disorders Seizures Sleep enhancement in healthy people (A) Stroke

Generally safe; seizures, disorientation, clotting problems with overdose May cause sleepiness, headache, mood changes, blood pressure drop, and hyperglycemia in type 1 diabetics May alter other hormone levels Levels may increase with CYP1A2 inhibitors: amiodarone, cimetidine, ciprofloxacin, SSRIs, TCAs, clarithromycin, erythromycin, ethinyl estradiol, isoniazid May augment effects of sedatives Avoid with antiseizure medications, especially in children May augment methamphetamine side effects May enhance isoniazid as TB treatment

Methylsulfonylmethane (MSM) Metabolite of dimethylsulfoxide Source of sulfur for amino acids Found in horsetail, algae, fruits, grains

Arthritis Chronic pain Gum disease Rhinitis Scars, stretch marks Scleroderma Snoring (nose drops)

No adverse effects or drug interactions reported Limited research into efficacy

Continued

e23

52




Uses/Efficacy


N-acetylcysteine (NAC) Derivative of the amino acid l-cysteine Precursor of antioxidant, glutathione Decreases inflammatory mediators

Acetaminophen, carbon monoxide, and other poisonings (A) Alzheimer’s (−) Angina Atelectasis (A) Cancer treatment (−) for head, neck, lung cancer Cardioprotection Cystic fibrosis (A) Mucolytic (A) Pulmonary disease

Significant GI distress for some patients when taken orally Can decrease effectiveness of charcoal Severe headache and hypotensive effect taken with nitroglycerine

NADH (reduced nicotinamide adenine dinucleotide) Involved in the production of ATP from glucose

Cardioprotection Chronic fatigue Dementia Depression Jet lag Mental performance

No evidence of adverse effects or drug interactions

Omega-3 fatty acids Contain docosahexaenoic and eicosapentaenoic acids, essential fatty acids Tend to be metabolized into antiinflammatory compounds Alpha-linolenic acid also considered omega-3 acid (see entry)

Bipolar disorder CAD prevention (A) Cancer anorexia (−) Colon cancer Cyclosporine toxicity in transplant patients (A) Diabetes (−) Hypercholesterolemia (−) Hypertension (A) Hypertriglyceridemia (A) IBD Lupus Preeclampsia Rheumatoid arthritis (A)

Greater than 3 g/day may increase bleeding risk Tend not to contain heavy metals GI upset common (5%); may help to change brands No significant long-term glucose effects Increased LDL levels by 5%-10% Rare reports of increase liver enzymes

Phosphatidylserine Most abundant fat-soluble phospholipid in brain, used for signal transduction, membrane stability Most is obtained from foods

ADHD Age-related cognitive impairment Athletic performance Dementias Depression

No adverse effects or drug side effects noted Lowers ALT level

Probiotics Bacterial compounds ingested to fortify or replenish populations of healthy gut flora Most species used are lactobacilli, bifidobacteria, and the yeast S. boulardii (related to baker’s yeast)

Bacterial vaginosis (A) Diarrhea prevention (A): Clostridium difficile, irritable bowel syndrome; IBD “Leaky gut” prevention and treatment (absorption of large, allergenic molecules through GI tract) Lipid disorders Rotavirus treatment

Caution in severely immunocompromised patients Take 2-3 hours after antibiotic to avoid killing organisms May reduce effectiveness of sulfasalazine May prolong effects of benzodiazepines or oral contraceptives (theoretic) Products are variable regarding number of live organisms

Quercetin Bioflavonoid (rutin is a derivative) Antioxidant, anti-inflammatory, and antihistamine properties In vitro decreases of T-cell and cancer cell growth

Allergies Atherosclerosis Cancer prevention Lipid disorders Prostatitis

Orally: can cause headache, tingling of extremities IV: can cause flushing

Ribose Pentose sugar supplied by pentose phosphate pathway Precursor for adenine nucleotide synthesis

Athletic performance Enhance energy Heart failure Myocardial ischemia Stiffness after exercise

Can decrease blood glucose levels and may enhance glucose-lowering effects of drugs

e24




Uses/Efficacy


SAMe (SAM-e) (S-adenosyl-l-methionine) Often called “sammy” Found in all body tissues and fluids, used in >100 transmethylation reactions May stimulate cartilage growth

Alcoholic liver disease Dementia Depression (“A” for major depression treated IV) Fibromyalgia Low back pain Osteoarthritis (A) Premenstrual syndrome

Can precipitate manic episodes in bipolar patients Metabolized to homocysteine, but not shown to elevate serum homocysteine levels May augment serotonergic effects of SSRIs, meperidine Caution with MAOIs May counteract effects of levodopa in Parkinson’s disease

Shark cartilage

Arthritis Cancer (−) Macular degeneration Pain

Generally safe May contain high levels of calcium May block formation of collateral vessels Frequent GI side effects

Data from Basch EM, Ulbricht CE. Natural Standard Herb and Supplement Handbook: The Clinical Bottom Line. Boston, Elsevier-Mosby, 2005; Mahan LK, Escott-Stump S (eds). Krause’s Food Nutrition and Diet Therapy, 11th ed. Philadelphia, Saunders-Elsevier, 2004; and Natural Medicines Comprehensive Database (accessed November 2009). *Many of the nutraceuticals listed are used for dozens of different indications; only the most common (and when possible, most researched) indications are listed. Lack of randomized controlled trial (RCT) research is not equivalent to lack of efficacy. An “A” in parentheses after a supplement name denotes an A rating according to the Strength of Recommendation Taxonomy (SORT). The rating is based on systematic review data summarized primarily in the references by Basch and/or Natural Medicines Comprehensive Database (NMCD). A classification of “A” is assigned if the supplement was rated as one of the following: (1) evidence grade A or B in Basch (indicating strong or good evidence of effect) or (2) rating of “Effective” or “Likely effective” in NMCD, suggesting the same. Not all supplement monographs reach the same conclusions regarding the evidence base for particular supplements. Indications followed by a “(−)” have been rated category D by Basch (indicating “Fair negative scientific evidence”) or as “Likely ineffective” by NMCD. Adverse effects or interactions preceded by “May” are speculative. No case reports or trials have verified their existence. ACE, Angiotensin-converting enzyme; ADHD, attention-deficit hyperactivity disorder; ALT, alanine transaminase; ATP, adenosine triphosphate; CAD, coronary artery disease; CHF, congestive heart failure; CYP, cytochrome P-450; FDA, Food and Drug Administration; GABA, γ-aminobutyric acid; GI, gastrointestinal; HIV, human immunodeficiency virus; IBD, inflammatory bowel disease; IV, intravenously; LDL, low-density lipoprotein; MAOIs, monoamine oxidase inhibitors; MI, myocardial infarction; REM, rapid eye movement; SSRIs, selective serotonin reuptake inhibitors; TB, tuberculosis; TCAs, tricyclic antidepressants; TMJ, temporomandibular joint; TPN, total parenteral nutrition.

frequently used supplements in 2007, combination supplements were ranked sixth (Kennedy et al., 2008). In Chinese herbal formulations, at least eight different compounds may be mixed together, and the same may be true for Ayurvedic and other remedies. Many products contain a mix of botanicals, vitamins and minerals, and nutraceuticals. In addressing questions or safety issues related to mixed supplements, it is important to consider each ingredient separately, based on the guidelines listed in Box 52-1. It should be remembered that there are often instances where products used in combination may have a synergistic—or occasionally an antagonistic—effect on one another. Table 52-7 lists a number of supplements that have particularly strong research supporting their use.

EVIDENCE-BASED SUMMARY • D ietary supplements, including those that are nonvitamin and nonmineral, are widely used (Strength of Recommendation Taxonomy [SORT] Grade A). • Many people do not inform their physicians about their supplement use (SORT A). • It is beneficial for family physicians to be well versed in advising patients regarding dietary supplements (SORT C). • The body of good-quality research related to dietary supplements is increasing, with studies showing variable levels of efficacy depending on the supplements evaluated (SORT A).

e25

52


Table 52-7 Supplements with Particularly Strong Research Supporting Their Use*

Supplement

Indication

Citation(s)

Cat’s claw

Joint pain

Erowele and Kalejaiye, 2009; Piscoya et al., 2001

Coenzyme Q10

Hypertension (~17 mm Hg systolic, 10 mm Hg diastolic)

Rosenfeldt et al., 2007

Cranberry

Urinary tract infection prophylaxis

Jepson and Craig, 2008

Ginger

Nausea and vomiting in pregnancy

Smith et al., 2004; White, 2007

Glucosamine sulfate†

Delay of arthritis progression (especially in knee)

Black et al., 2009; Towheed et al., 2005

Hawthorn

Stage I or II heart failure

Pittler et al., 2008

Horse chestnut

Chronic venous insufficiency

Pittler and Ernst, 2006

Melatonin

Jet lag; sleep in individuals with intellectual disability

Bram et al., 2009; Herxheimer and Petrie, 2005

Milk thistle

Cirrhosis

Saller et al., 2001

Omega-3 fatty acids‡

Hypertriglyceridemia

Laidlaw and Holub, 2003

Peppermint oil

Irritable bowel syndrome

Merat et al., 2009

Probiotics

Irritable bowel syndrome (especially Bifidum infantis); antibioticassociated diarrhea; traveler’s diarrhea)

Brenner et al., 2009; Doron et al., 2008; McFarland, 2007

St. John’s wort

Mild to moderate depression

Linde et al., 2009

Valerian

Insomnia (some studies show only modest overall benefit)

Bent et al., 2006; Hadley and Petry, 2004

*All herbs listed have Strength of Recommendation (SOR) classification of A. †In many cases, although much favorable evidence exists for various supplements, including those listed, meta-analyses often reveal discrepancies among trial findings. With glucosamine, for example, an overall benefit was seen using some osteoarthritis symptom scales with and using some products (the sulfate form seems to be more effective than glucosamine hydrochloride). For many of the supplements mentioned in this chapter, it is difficult to say with absolute certainty that efficacy has consistently been proven. Of course, the same often holds true for pharmaceuticals. It is important that family physicians also note the potential risk to the patient when using a given supplement. For example, glucosamine was found to be equivalent to placebo in terms of adverse effects, and St. John’s wort tends to have fewer side effects than antidepressants. ‡Although omega-3 fatty acids are now recommended by the American Heart Association for the treatment of lipid abnormalities, “It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events, or cancers in people with or at high risk of cardiovascular disease in the general population” (Hooper et al., 2006). Again, the question becomes how to interpret the available data in a clinically meaningful way. Harms from omega-3 fatty acids appear to be minimal.

Web Resources http://nccam.nih.gov/health/herbsataglance.htm National Center for Complementary and Alternative Medicine site on herbs. www.cfsan.fda.gov/~dms/ds-savvy.html Good overall patient handout regarding safe use of supplements. www.naturaldatabase.com Subscription site offering up-to-date monographs on most popular supplements; lists ingredients for different commercial products and allows search by indication as well. Evidence for efficacy rated when available. www.consumerlab.com Charges small subscription fee, which is used to support research evaluating whether or not supplements contain the components their labels claim. Findings can often be a concern from a product quality standpoint. www.naturalstandard.com Subscription site with excellent bibliographic data for various supplements.

e26

www.drugdigest.org Free site, searchable by supplement or drug names and indications. The user can create a list of medications and supplements and check for any interactions between/among products in that list. Useful site to recommend to patients. www.phytotherapies.org Free site with registration, geared toward herbalists and professionals who prescribe botanicals; numerous monographs on different herbal supplements, as well as current news stories. www.mdanderson.org/departments/CIMER Well-designed free site by the University of Texas M.D. Anderson Cancer Center. Searchable for evidence related to supplements as well as research relating to other complementary and alternative/ integrative medicine modalities. Supplement information is primarily for botanicals. http://ods.od.nih.gov/index.aspx National Institutes of Health Office of Dietary Supplements; has a series of well-done monographs, a number of which focus on vitamins and other nonherb supplements.

Herbs and Other Dietary Supplements www.herbs.org Herb Research Foundation; site is free but funded by registration fees; has useful news updates. http://www.americanherbalistsguild.com/ American Herbalist Guild; click on “Find an Herbalist” to look for guild members to whom referrals could be made. www.naturopathic.org. American Association of Naturopathic Physicians; click on “Find” at the top of homepage to find “naturopaths” in a particular city or state.

www.InteractionReport.org/ Website for submitting case reports of supplement-related interactions. All websites accessed November 2009. Refer also to texts and articles cited in online references for this chapter. Note that supplement information, particularly for herbs, vitamins, and minerals, is offered now in “mainstream” medical resources and databases, such as UpToDate, MDConsult, Epocrates, MedLine, and the Family Practice Inquiries Network (FPIN).

e27

Index

A Abacavir, 258t Abandonment of elderly, 41t and terminal illness, 58 Abdomen of newborn, 408 distended, 413 physical examination, 844 Abdominal aortic aneurysm, 83 Abducens nerve (CN VI), 960 Ablation, for arrhythmia, 544–545 Abnormal puberty, 785–787 Abnormal vaginal bleeding, 456–459 adolescents, 457 perimenopausal women, 458–459 postmenopausal women, 459 reproductive-age women, 457–458 Abortion, spontaneous, 376–377 Abruptio placentae, 380 Abscess anorectal, 568 bacterial skin infections, 707 Bartholin’s gland, 571 brain, 244, 983–984 cutaneous, incision and drainage, 564–565 orbital, 325t peritonsillar, 301–302 Absolute neutrophil count (ANC), 188, 890t Absorbable sutures, 553 Absorption of fatty acids, 825t of lipid and cholesterol, 483f of nutrients, 824 Abuse alcohol. See Alcohol abuse drug. See Drug abuse of elderly, 39–42 intimate partner. See Intimate partner violence substance, 84–86, 1028t–1029t. See also Substance use disorder diagnostic criteria, 1124b Acamprosate, 1101 Accelerated atherosclerosis, 752 Accelerated platelet removal, caused by immune destruction, 893–894 Accelerations, FHR, 391 Acceptable macronutrient distribution range (AMDR), 841 Accessibility of family physician, 12 Accommodative esotropia, 943f Accuracy of screening tests, expressing, 76 Acellular pertussis vaccine, 438–439

Acetaminophen codeine with, for pain control, 61t exposure, in pregnancy, 369t Acetylcholinesterase (ACE) inhibitors effect on therapy in anaphylaxis, 357t exposure in pregnancy, 369t N-Acetylcysteine (NAC), 1155t–1159t Acetyl-L-carnitine, 1155t–1159t Achilles tendinopathy, 628 Acne conglobata, 697f Acne fulminans, 696f Acne vulgaris, 695–697 Acoustic energy, hearing loss from, 317 Acoustic neuroma, 316–317 Acquired cataracts, 950 Acquired cholesteatomas, 315 Acquired immunodeficiency syndrome (AIDS) epidemiology, 248–249 infections related to, 284–287 Acral lentiginous melanoma, 729f Acromioclavicular joint injuries, 604, 605f Actinic keratosis, 724–725 Action potentials, 533–534 Activase, 507t Activated partial prothrombin time (PTT), 185 Active listening, 108–109 Active phase of first stage of labor, 384 protracted, 388 Activity changes, and obesity, 807 Acupuncture, 141–144 Acute adrenal insufficiency, 779 Acute bronchitis, 279 Acute chest syndrome, 290–291 Acute coronary syndromes, unstable angina/ non-ST segment MI, 503–505 Acute cutaneous LE, 720 Acute exacerbation of asthma, 270, 353 of chronic bronchitis, 209 of COPD, 275–276 Acute gonococcal arthritis, 675–676 Acute inflammatory demyelinating polyradiculoneuropathy, 992 Acute mountain sickness, 588 Acute otitis media, 311–313 Acute pancreatitis, 861–862 Acute pharmacologic therapy, of STEMI, 508b Acute pharyngitis, 330–332 Acute-phase reactants, 189–190 Acute respiratory failure, 277 Acute sinusitis, medical treatment, 325–327 Acute stress disorder, 1028t–1029t Acute urinary incontinence, 48 Acyclovir, for HSV infection, 220t Adaptation to crisis, 1027

Page numbers followed by f indicate figures; b, boxes; t, tables.

Adaptive capacity, 27–28 Adaptive coping styles, 1033b Adaptive problem solving, 1032 Adderall. See Amphetamine salts Addiction alcohol, stages of change in, 1098 nicotine cravings, 1105–1106 gene methylation, 1121 health risks, 1106–1116 smoking cessation, 1116–1121 Adenocarcinoma, esophageal, 847–855 Adenoid hypertrophy, 321 Adenomas pituitary, hyperfunctioning, 761–762 pleomorphic, 341 S-Adenosyl-L-methionine (SAM-e), 1155t–1159t Adequate intake, 841 Adherence to treatment by difficult patients, 1044t–1047t for TB, 284b Adhesives, skin, 559–560 Adjunctive therapy, for pressure ulcers, 44–45 Adjustment disorder, 1028t–1029t Adolescents abnormal vaginal bleeding, 457 alcohol abuse among, 1103 asthma severity in, 272f BMI, 428 in clinical interview, 173 CRAFFT screening tool for, 1126t with diabetes, supportive care, 743–744 hematuria, 906–907 nutrition, 430–431, 828 preventive services for, 90–91 proteinuria, 908 sexuality issues, 1009–1011 with substance use disorders, 1133 Adolescents: behavioral problems conduct disorder, 450 eating disorders, 452 ODD, 450 sleep problems, 443–445 Adrenal glands androgen production, 777 disorders of cortical hyperfunction aldosteronism, 782–783 Cushing’s syndrome, 780–781 disorders of cortical hypofunction primary adrenal insufficiency, 778–779 secondary and tertiary adrenal insufficiency, 779–780 pheochromocytoma, 783–784

Index Adrenal insufficiency primary, 778–779 secondary, 759 and tertiary, 779–780 Adrenalitis, autoimmune, 778 Adrenal medulla, disorders of hyperfunction, 783–784 Adrenergic inhibitors for hypertension, 487t–489t for hypertensive emergencies, 491t Adrenocorticotropic hormone (ACTH), 757, 760, 777 Adults with asthma, step therapy, 352f CAGE-AID screening tool for, 1126t in clinical interview, 173 elderly. See Elderly patients first seizure, initial diagnostic evaluation of, 974 GI disorders esophagus, 847–848 stomach and duodenum, 848–855 gross hematuria, 904–905 management of obesity, 811–812 microscopic hematuria, 905–906 nutrition, 830–831 older. See Older adults ophthalmology correction of refractive errors, 947 ocular medications, 948 strabismus in, 949 proteinuria, 908, 909f red eye in, 932–936 renal calculi, 918 with suspected bacterial meningitis, 977t use of CAM, 135f–137f Advance directives, 69–71 Adverse drug events antiepileptics, 976t in elderly, 45–47 Aerobic vaginitis, 463 Affect, intense, 1048 Age, and incidence of overweight, 806 Age-related changes ocular, 950 in urinary system, 48 Aging nutritional needs and, 831 and pharmacokinetics, 45 and prevalence of PVD, 520 Agitation, with alcohol withdrawal, 1096t–1097t Agnogenic myeloid metaplasia with myelofibrosis (AMM/MF), 888 Airway, foreign bodies in, 302–303 Alanine aminotransferase (ALT), 180–181 Albumin laboratory test, 180, 827 Alcohol in diabetes mellitus, 737 intoxication, 1094–1099 unhealthy alcohol use, assessing for, 172 Alcohol abuse among adolescents, 1103 biologic markers, 1093 preventive services for, 84–85 psychiatric evaluation, 1094 Alcoholic neuropathy, 993 Alcoholism treatment, 1095, 1099–1101

1136

Alcohol use disorders biologic markers, 1093 cirrhosis of liver, 1091–1092 detailed assessment, 1094 interview questions, 1093–1094 management, 1094–1099 among older adults, 1103 physical assessment, 1094 among physicians, 1103 prevalence, 1092 prevention, 1104 screening and assessment, 1092–1094 treatment of alcoholism, 1099–1101 in women, 1101–1102 Alcohol withdrawal syndrome, 1095–1096 Aldosterone blockers, for CHF, 511–512 Aldosterone suppression testing, 782–783 Aldosteronism, 782–783 Alfuzosin, 51t Alginate wound dressings, 45t Alkaline phosphatase (ALP), 180, 181t Alkylating agents, for rheumatoid arthritis, 664t–665t Allergic conjunctivitis, 934 Allergic contact dermatitis, 702–703 Allergic rhinitis, 322–323 association with nasal polyps, 346 treatment, 344–346 Allergic vaginitis, 463 Allergy. See also Asthma anaphylaxis, 354–357 in eye, 346–347 hypotheses, 343 paradoxical vocal cord motion, 353 shots, in pregnancy, 369t Allopurinol, 670 Aloe, 1142t–1147t Alpha-adrenergic antagonists, for incontinence, 51t Alpha blockers effect on lipid values, 195t for hypertension, 487t–489t Alpha-lipoic acid, 1155t–1159t Alternative medicine, 132 Altitude illness, 588 Alzheimer’s disease, 971, 1084–1087 pharmacotherapy, 1085–1086 smoking as risk factor, 1112 Amantadine, for influenza, 213t Amaurosis fugax, 956–957 Amblyopia, 941–943 Amenorrhea, 458, 790–793 athletic, 599–600 American Board of Family Medicine, 5 Amides, 551b Aminotransferases, 180–181 Amitriptyline, in elderly, 46t Amnesia, in sports concussion, 582–583 Amniocentesis, 367 Amoxicillin, for acute otitis media, 312t Amoxicillin/clavulanate, 233t Amphetamines, detection time, 1127t Amphetamine salts, 449t Ampicillin, for bacterial meningitis, 244t Amylase laboratory test, 181 Amylin, 741 Anal fissure, 568–569 Analgesics, for pain control, 60

Anaphylaxis manifestations, 354 treatment, 355–357 Anaplasma phagocytophila, 228, 229t Androgens deficiency in adult males, 1011–1012 effect on lipid values, 195t excess in women, 795b production, 777 Anemia, 187 of chronic disease, 194t clinical features, 880–881 definition, 879 effect on ESR, 190t of inflammation, 882 iron deficiency, 193 laboratory tests, 881–882 physiologic classification, 882–886 in pregnancy, 371–372 prevalence, 879–880 sports, 593 Anesthesia obstetric, 395–396 types of, for office procedures, 553–555 Aneurysm, abdominal aortic, 83 Angina stable, 499–503 unstable, 503–505 Angiography baseline, femoral artery, 532f for PVD, 527–529 Angioplasty, coronary, 503 Angiotensin-converting enzyme (ACE) inhibitors for CHF, 510, 511t for hypertension, 487t–489t Angiotensin II receptor blockers, for hypertension, 487t–489t Angiotensin receptor blockers, for CHF, 510–511 Angle-closure glaucoma, 936 Animal bites, 235, 238t–239t Anion gap, 188 Ankle-brachial index, 519, 525, 526f, 527t, 532f Ankle sprains, 624–627 Ankylosing spondylitis, 672–673 Anorectal disease abscess, 568 anal fissure, 568–569 anoscopy, 566 hemorrhoids, 566–568 pilonidal cyst and abscess, 569 Anorexia nervosa, 452–453 Anoscopy, 566 Anovulatory cycles, 457b Antepartum fetal surveillance biophysical profile, 383 contraction stress test, 383 nonstress test, 382–383 vibroacoustic stimulation, 383–384 Anterior cruciate ligament injuries, 623–624 Anterior ischemic optic neuropathy, 956 Anterior packing, for epistaxis, 304 Anterior polar cataracts, 945 Antiarrhythmic drugs, 545t–547t Antibiotic-associated diarrhea, 246–247

Index Antibiotics for bacterial meningitis, 244t, 982t resistance to, 326 in treating bronchitis, 208 Anticholinergics dosing data, 66t for Parkinson’s disease medications, 996t for smooth muscle spasm, 65 Anticipatory guidance, 91 before discharge, 418–419 Anticonvulsants for alcohol dependency, 1101 dosing data, 66t for migraine, 964t Anti-cyclic citrullinated peptide (anti-CCP) antibodies, 199, 661 Anticytokine therapy, for rheumatoid arthritis, 665–666 Antidepressants discontinuation of treatment, 1072–1073 doses, 1052t failure of, 1073 selection, 1069–1072 and suicidal ideation, 1075–1076 tricyclic. See Tricyclic antidepressants Antidiabetic agents amylin, 741 developing therapies, 741 dipeptidyl peptidase inhibitors, 741 glycemic targets, 739 incretin agonist, 741 noninsulin, 740t oral agents, 739–741 Antidiabetic protocol, in hospital care, 749 Antiepileptics adverse effects, 976t effect on lipid values, 195t Antihistamines for allergic rhinitis, 322, 345 dosing data, 66t in elderly, 46t exposure in pregnancy, 369t Antihypertensives, oral, 487t–489t Anti-inflammatory diet, 141t Antimalarial drugs, for rheumatoid arthritis, 664t–665t Antimicrobial therapy in bacterial meningitis, 979t–980t for bite wounds, 238t–239t for CAP, 211t presumptive pathogen identification and, 978t for SSTIs, 233t Antimuscarinics, for incontinence, 51t Antinuclear antibodies (ANAs), 181–182, 680 Antioxidants, 1155t–1159t Antiphospholipid antibody syndrome, 680 Antiplatelet agents for stable angina, 502–503 in treatment of unstable angina, 505 Antipsychotics for delirium, 971, 1082 doses, 1052t Antiretroviral agents combinations to avoid, 258t for HIV/AIDS, 255–259 Antisocial personality disorder, 1041t–1047t, 1055

Antispasmodics, in elderly, 46t α1-Antitrypsin deficiency, 274 Anus, of newborn, 408–409 Anxiety with alcohol withdrawal, 1096t–1097t assessment of anxious patient in medical settings, 1067–1069 co-analgesics for, 66t differential diagnosis, 1068 disease course, 1061 drug therapy, 65 epidemiology, 1060–1061 generalized anxiety disorder, 1073–1075 health care costs related to, 1061 interaction with depression, 1062 medical illness interaction with, 1062–1063 neurobiology and genetics, 1061–1062 panic disorder, 1075 psychotherapy for, 1077 screening tools for anxiety disorders, 1066–1067 suicide screening and assessment, 1068–1069 treatment continuation in anxiety disorders, 1075 Aortic stenosis, 513–514 Aortic valve regurgitation, 514–515 Apgar score, 406 Apnea in neonate, 412 sleep, 298 obstructive, 333, 809 Apomorphine, 1007 Apophyseal injuries, in pediatric athletes, 598 Apoplexy, of pituitary, 758 Appendicitis, 846–847 Appendicolith, 847f Appetite modulation, 806–807 Apple core lesion, in colon cancer, 875f Apprehension test, 609f Aptivus. See Tipranavir Arava. See Leflunomide Arginine, drug interactions, 1155t–1159t Arginine vasopressin, 763 Arms, in body language, 155 Arrhythmias action potential, 533–534 in athletes, 580–581 cardiac conduction system, 531–533 ECG evaluation of, 535–536 mechanism of, 535 pattern recognition atrial rhythms, 536–538 AV node conduction disorders, 540 junctional rhythms, 538–539 paced rhythms, 541–542 ventricular rhythms, 541 surface action potential, 534 treatment, 544–549 Arterial blood gas (ABG) normal values in pregnancy, 373t testing, 266 Arthritis gouty, 670 infectious, 675–677 psoriatic, 674–675, 698 septic, 240, 675–676 of systemic disease, 654–655 Arthrocentesis, 575–576, 653–654

5As framework for behavioral counseling, 92–93 using in system, 94 Aspartate aminotransferase (AST), 180–181 Aspiration of breast cyst, 574 of knee joint, 575–576 uterine, 573 Aspirin exposure in pregnancy, 369t and risk for peptic ulcer disease, 850 Asterixis, 1080 Asthma bronchial, 263t clinical presentation and diagnosis, 269–270 diagnosis, 347–348 differential diagnosis, 274b epidemiology and risk factors, 269 exercise-induced bronchospasm, 353 peak flow monitoring, 348–349 in pregnancy, 372–373 prevention, 273 treatment, 270–271, 349–353 work-related, 293 Asymptomatic bacteriuria, 921 Asymptomatic hematuria, 905 Asymptomatic PVD, 519 Atazanavir, 258t Atelectasis, 263t Atherosclerosis, 479 accelerated, 752 natural history, 521 Atherosclerosis Risk in Communities Study, 105, 106t–107t Athletes cardiac disorders in, 580–582 female, special concerns for, 598–600 muscle and tendon injuries, 594–596 nonanemic, low ferritin in, 593 pediatric, 597–598 shin pain, 596–597 stress fracture, 597 warning symptoms in, 579 Atomoxetine, for ADHD, 449 Atopic dermatitis, 693–694 Atresia, choanal, 321 Atrial fibrillation, 538, 544 in athletes, 581 risk factor for stroke, 966 Atrial flutter, 538 Atrial myocytes, 533 Atrial rhythms, 536–538 Atrioventricular (AV) nodal reentrant tachycardia, in athletes, 581 Atrioventricular (AV) node complex, 533 Atrioventricular (AV) node conduction, disorders of, 540 Atrioventricular (AV) reciprocating tachycardia, 542–543 Atripla, 258t At-risk groups for influenza complications, 213b tuberculin positivity criteria by, 283b Atrophic rhinitis, 324 Atrophic vaginitis, 466 Attention deficit/hyperactivity disorder (ADHD), 446–450 management of, 447–450

1137

Index Atypical moles, excision of, 562–563 Audiology screening, of newborn, 410 Augmentation strategies, 1073 Aura, migraine with and without, 962–963 Auricular hematoma, 309 Auscultation for asthma, 269–270 in pulmonary medicine, 263 Autism assessment, 446 characterization of, 445–446 screening for, 435–436 Autoimmune diseases adrenalitis, 778 connective tissue disorders, lung manifestations of, 297 neutropenia, 890b Sjögren’s syndrome, 341 Autolytic debridement, for pressure ulcers, 44 Automated external defibrillators (AEDs), in athletic medicine, 582 Autonomic changes, in peripheral neuropathies, 987 Autosensitization reaction, to vesicular tinea pedis, 691f Avoidant personality disorder, 1041t–1047t, 1057 Axonal neuropathies, 987 Ayurveda, 142t Azathioprine, for rheumatoid arthritis, 665

B Babesiosis, 230 Babinski sign, 961 Baclofen, 1101 Bacteria, in urine, 902 Bacterial infections AIDS-defining illnesses, 251 articular, 675–676 conjunctivitis in adults, 933–934 in infants, 931 of knee, 618 meningitis, 243–244, 975–981 prostatitis, 919 in sports medicine, 592 vaginosis, 460–461 Bacterial skin infections, 705–707 abscesses, 707 cellulitis, 706–707 erysipelas (St. Anthony’s fire), 706 erythrasma, 707 folliculitis, 707 impetigo, 706 Bacteriuria, asymptomatic, 921 Balance, 961 Balanitis, 919 Ballard score, new, 410b Balloon valvuloplasty, mitral, 516b Barbiturates detection time, 1127t in elderly, 46t Bariatric procedures, for obesity, 815–817 Barley, 1142t–1147t Barlow’s maneuver, 409f Barotitis, 315 Barotrauma, 315

1138

Barrett’s esophagus, 847–855, 848f Barrier contraceptives, 470–472 Barriers to effective communication, 169–170 Bartholin’s gland, abscess or cyst, 571 Basal body temperature, method of contraception, 473 Basal bolus insulin, 743 Basal cell carcinoma, 563, 726–727 Baseline FHR, 390 Bathing of neonate, 418–419 Bed sharing, by neonate, 418 Behavior associated with trauma, 1024b atypical, by physician, 1049 health, in personality disorders, 1041t–1043t and neurodevelopment, 431 Behavioral approaches to incontinence intervention in elderly patients, 50 to obesity management, 814 Behavioral control, 28 Behavioral counseling, 5As framework for, 92–93 Behavioral modification, to improve diet and lifestyle, 838–840 Behavioral problems in children and adolescents ADHD, 446–450 autism, 445–446 conduct disorder, 450 eating disorders, 452 general principles for evaluation, 442 ODD, 450 sleep problems, 443–445 Behavioral symptoms accompanying dementia, 1089 Behavioral therapy for diabetes mellitus, 736 for substance use disorders, 1131–1132 Behavior change diet counseling and, 839 model of, 161–162 in smoking cessation, 1117 theories and models of, 93–94 Bell’s palsy, 318 Benign findings in newborn, 407b Benign paroxysmal positional vertigo, 307–308 Benign positional vertigo, 985 Benign prostatic hyperplasia (BPH), 51–52, 924 Benign skin growths dermatofibroma, 724 epidermal inclusion cysts, 724 pyogenic granuloma, 723–724 seborrheic keratosis, 723 Benzodiazepines detection time, 1127t in elderly, 46t for GAD, 1074 intoxication and withdrawal, 1130 for panic disorder, 1075 pharmacology, 1129 side effects, 1071t street names for, 1125t Beta blockers and aging, 45 for CHF, 511t in CHF, 512

Beta blockers (Continued) complicating therapy in anaphylaxis, 357t effect on lipid values, 195t for GAD, 1074–1075 for hypertension, 487t–489t for stable angina, 502 Bethanechol, 51t Bicarbonate, laboratory test, 188–189 Bilberry, 1142t–1147t Bile acid-binding resins, 483–484 Biliopancreatic diversion, 815 Bilirubin laboratory test, 182–183 Bioflavonoids, 1155t–1159t Biologic factors, in biopsychosocial model, 25 Biologic markers, of alcohol abuse, 1093 Biologic variability, 176 Biophysical profile, in antepartum fetal surveillance, 383 Biopsy cervical, 572 endometrial, 572–573 fine-needle aspiration. See Fine-needle aspiration biopsy (FNAB) of granuloma inguinale lesion, 222f for lung cancer, 291 transbronchial, 295 Biopsychosocial model, 25–27 Biotin interactions, 1147t–1154t nutritional summary, 820t–824t Bipolar depression features suggesting, 1065t vs. unipolar depression, 1064–1065 Bipolar disorder, 1064 screening for, 1065–1066 Birth trauma, 416–417 Bisexual patients, 1008 Bishop’s pelvic scoring, for labor induction, 387t Bisphosphonates, 599 Bite infections, 235 care of, 551–552 management, 238t–239t Black cohosh, 1142t–1147t Black eye, 938 Bladder cancer, 924–925 smoking-related, 1110 overactive, 917 Bleeding lower GI, 868–870 massive acute rectal, 871t upper GI, 852–855 vaginal, abnormal, 456–459 Blepharitis, 933 Block with reentry, 535 Blood gases, measurement for pulmonary medicine, 266 Blood pressure adult, 82t effects of herbs, 1141b elevated, in stroke, 969 JNC-7 classification, 486t monitoring in children, 422 in neonate, 411–412 tips for attaining goal, 490b Blood urea nitrogen (BUN), 183 Blue-green algae, 1142t–1147t

Index Blunt eye injuries, 938–939 Body composition, 826 Body dysmorphic disorder, 1040b, 1041t–1047t, 1058 Body fat percentage, 804 Body language, 150–157 Body lice, 718 Body mass index (BMI) for children and teenagers, 423, 428, 430 obesity and, 804t primary prevention and, 103 weight categories according to, 826t Body position, in body language, 151 Bone age, relationship to short stature, 424b Bone density, in female athlete, 599 Bone disease ALP increase due to, 181t orthopedic hardware infections, 239–240 osteomyelitis, 237–239 Bone marrow, cellular elements in, 878f Bone pain, co-analgesics for, 61–65, 66t Bone regions, 602f Borderline personality disorder, 1041t–1047t, 1056–1057 Boron, supplements, 1147t–1154t Borrelia burgdorferi, 230 Botanicals, 1141 Bowen’s disease, 725–726 Bowstring sign, 638f Brachial plexus injuries, in newborn, 417 Brachial plexus neuropathy, 989–990 Bradycardia, FHR, 390–391 Brain abscess, 244, 983–984 Branchial cleft cysts, 339 Breast cancer, 79–80 and CEA level, 184t genomic applications, 1014t hereditary, 1019–1020 Breast milk, human, 429 Breast(s) cyst, aspiration, 574 female, sexual maturity stages, 425t mass, 573 Breathing disorders, 298–299 Brief intervention, in alcohol disease, 1098–1099 Bronchiectasis, 278 differential diagnosis, 274b Bronchiolitis, in children, 278–282 Bronchitis acute, 279 chronic, 209 treating with antibiotics, 208 Bronchoalveolar lavage (BAL), 266 Bronchoscopy, 266 Bronchospasm, exercise-induced, 353, 592–593 B-type natriuretic peptide (BNP), 196 Bulimia nervosa, 452–453 Bulking agents, periurethral injection, 52 Bullous myringitis, 311 Bundle branch network, 533 Buprenorphine, 1131 Bupropion, 1071t, 1119b, 1120 Burden of disease for abdominal aortic aneurysm, 83 for alcohol use, 84–85 for breast cancer, 79

Burden of disease (Continued) for cervical cancer, 79 for CHD and CVA, 83 for chlamydial infection, 86 for colorectal cancer, 77 for depression, 85 for diabetes mellitus type 2, 88 expression of, 76 for gonorrheal infection, 87 for healthy diet counseling, 90 for HIV, 87–88 for hyperlipidemia, 81–82 for hypertension, 81 for lung cancer, 80 for obesity, 89 for osteoporosis, 89 for ovarian cancer, 80 for physical activity counseling, 90 for prostate cancer, 81 for tobacco use, 84 Burns, chemical, ocular, 936 Bursae, around knee, 619f Bursitis of knee, 618 olecranon, 611–612 Buspirone, 1074–1075 Bypass surgery, for stable angina, 503

C CAGE questions, 1092, 1093b Calciferol (vitamin D2), 204 nutritional summary, 820t–824t Calcification(s) pancreatic, 863f vascular, 525 Calcium abnormalities, 184t laboratory test, 183 nutritional summary, 820t–824t supplements, 830t, 1147t–1154t Calcium antagonists, for hypertension, 487t–489t Calcium channel blockers for migraine, 964t for stable angina, 502 Calcium disturbances hypercalcemia, 796–799 hypocalcemia, 799 Calcium pyrophosphate deposition disease, 671 Calculi, renal, 918 Calendar method of contraception, 472 Caloric intake, and obesity, 807 Caloric requirements, for hospitalized patient, 837 Caloric restriction, 830 Cancer. See also specific cancers correlation with obesity, 809 HIV-associated, 252 prevention through nutrition, 830 preventive services, 77–81 related to smoking, 1106–1110 top 15 cancer sites, age-adjusted U.S. death rates for, 78t Candidal vaginitis, 461–462 Caplan, Gerald, 1023 Capsule endoscopy, 875–876

Carbidopa-levodopa combinations, 996t Carbohydrate-deficient transferrin (CDT), 1093 Carbohydrates, nutritional summary, 820t–824t Carbon dioxide (CO2), laboratory test, 188–189 Carbuncles, 232–234, 707 Carcinoembryonic antigen (CEA), 183–184 Carcinomas, in SIADH, 765b Carcinomatous neuropathies, 994 Cardiac conduction system, 531–533 Cardiopulmonary resuscitation (CPR), 70–71 Cardiovascular disease atherosclerosis, 479 cardiac electrophysiology and arrhythmias, 531–549 cigarette smoking and, 498–499 congestive heart failure, 508–513 coronary artery disease, 499–508 C-reactive protein and, 497–498 diabetes mellitus, 495–497 diet in prevention of, 833 dyslipidemia, 479–486 homocysteine and, 498 hypertension, 486–492 metabolic syndrome, 492–495 peripheral arterial disease, 518–531 possibly causing delirium, 1080b risk factors for, 82f smoking-related, 1111–1112 U.S. mortality due to, 478 valvular heart disease, 513–518 Cardiovascular manifestations of SLE, 680 Cardiovascular screening, in PPE: limitations, 579–580 Cardiovascular system, linked to shortness of breath, 267 Caregivers, of Alzheimer’s patients, 1087 Care management support, 121 Caring, 7 Carotid artery disease, TIAs in, 956–957 Carotid artery stenosis, risk factor for stroke, 966 Carotid body tumors, 340 Carpal tunnel syndrome, 612–613, 990 Car seats, infant, 418 Case-control studies, in HRT, 113 Casts, in urine, 901–902 Cataracts in adults, 950–951 pediatric, 945–946 smoking as risk factor, 1113 Catastrophic cervical spine injury, 585–586 Catechol-O-methyltransferase (COMT) inhibitors, 996t Cather-associated UTI, 227 Cat’s claw, 1142t–1147t, 1161t Cat-scratch disease, 340 Cautery, endoscopic, for epistaxis, 304–305 Cavernous hemangioma, 696f Cayenne, 1142t–1147t CD4+ cells, HIV and, 250, 252t, 253, 257t Ceftazidime, for bacterial meningitis, 244t Celiac disease, 825t, 872–873 Cell adhesion molecules (CAMs), 479

1139

Index Cellulitis, 231–234, 706–707 orbital, 935 periorbital, 325t preseptal, 935 Central (GnRH-dependent) precocious puberty, 787 Central hearing loss, 316 Central hypothyroidism, 772 Central nervous system (CNS) infections bacterial meningitis, 243–244, 975–981 brain abscess, 244, 983–984 chronic meningitis, 983 possibly causing delirium, 1080b recurrent meningitis, 981 viral encephalitis, 244 viral meningitis, 983 Central nervous system (CNS) lesions, in SIADH, 765b Central retinal artery occlusion, 936 Cephalexin, 233t Cephalohematoma, in newborn, 417 Cephalosporins, exposure in pregnancy, 369t Cerebral edema, in stroke, 969 Cerebrospinal fluid (CSF) findings, in meningitis, 978t leakage, nasal trauma and, 330 Cerebrovascular accident (stroke) acute intervention, 967–968 in diabetes, 753 first-line antiplatelet agents, 965 management of acute stroke, 968–970 pharmacologic therapy, 968 risk factors, 966–967 smoking, 1111–1112 Cerebrovascular disease, diet in prevention of, 833 Certification, in specialty, 5 Cerumen, 310–311 Cervical cancer, 79 smoking-related, 1110 Cervical cap, 471–472, 569–570 Cervical dilation, secondary arrest of, 388 Cervical lymphadenitis, 340 Cervical spine anatomy, 631 cervical radiculopathy, 634–636 dizziness originating in, 986 injuries, in sports, 584–586 physical examination, 631–634 strains and sprains, 634 torticollis, 634 Cervicitis, 222–224 Cesarean delivery, vaginal birth after, 393–395 Chalazion, 933 Challenges in evidence-based prevention, 75–76 Chancroid, 222, 919 Checklist for health home, 22 school-age child, 437t Chédiak-Higashi syndrome, 890 Chemical burns, ocular, 936 Chemical exposure in pregnancy, 368–369 teratogens, 403b Chemoprophylaxis, for influenza, 213t Chemotherapy, in terminal illness, 54–55 Chest, of newborn, 408

1140

Chest x-ray for COPD, 275 in pulmonary medicine, 264–266 Chickenpox, 697f Children with asthma management, 352–353 step therapy, 351f athletes, 597–598 bronchiolitis in, 278–282 in clinical interview, 172–173 with diabetes, supportive care, 743–744 diarrhea and dehydration, 844–846 differential diagnosis of FUO, 241b effects of secondhand smoke, 1115 exposed to intimate partner violence, 1025 health, 360–361 hearing loss, 317 hematuria, 906–907 ophthalmology. See Pediatric ophthalmology overweight and obesity, 810–811 preventive services for, 90–91 proteinuria, 908, 909f renal calculi, 918 rheumatic disease in, 687–688 signs of pneumonia in, 280 sinusitis, 328–329 skin problems beginning in childhood, 693–697 use of CAM, 135f–137f UTI in, 227, 922–923 Children: behavioral problems ADHD, 446–450 autism, 445–446 conduct disorder, 450 eating disorders, 452 ODD, 450 sleep problems, 443–445 Children: growth and development behavior and neurodevelopment, 431 blood pressure monitoring, 422 care of children in family medicine, 421–422 clinical assessment guidelines, 431–437 developmental milestones in young children, 434t–435t discipline, 427–428 immunizations, 437–441 measuring physical parameters of growth, 423–425 nutrition, 428–431, 828 screening healthy children, 425–427 Chlamydial infection causing ophthalmia neonatorum, 931 preventive services, 86–87 reactive arthritis secondary to, 674 Chlamydia screening, 219t Chlamydia trachomatis, 222–223 Chloride laboratory test, 184–185 nutritional summary, 820t–824t Chlorpropamide, in elderly, 46t Choanal atresia, 321 Cholecalciferol (vitamin D3), 204 supplements, 1147t–1154t Cholecystitis, 855–856 Cholelithiasis, 855–856

Cholesteatoma, 315 Cholesterol, lipid profile, 194 Choline, uses of, 1155t–1159t Cholinergic agonists, for incontinence, 51t Chopra, Depak, 106–107 Chorionic villus sampling, 367 Choroidal melanoma, 951–952 Chromium nutritional summary, 820t–824t supplements, 1147t–1154t Chromosomal disorders, 1019t Chronic adrenal insufficiency, 778–779 Chronic autoimmune thyroiditis, 771–772 Chronic bacterial prostatitis, 228 Chronic care of asthma, 270–271 of COPD, 276 Chronic care model, 94–95 Chronic exertional compartment syndrome, 596–597 Chronic hypertension, in pregnancy, 373–374 Chronic illness, 9 and psychosocial intervention, 30 rank order of chronic conditions, 15t Chronic inflammatory demyelinating polyradiculoneuropathy, 992 Chronic kidney disease, 912–913 Chronic meningitis, 983 Chronic obstructive pulmonary disease (COPD), 208 clinical presentation, 274 diagnosis and staging, 274–275 epidemiology and risk factors, 273–274 prevention, 276–277 smoking-caused, 1110 treatment, 275–276 Chronic pancreatitis, 862–863 Chronic pelvic pain, 464–466 Chronic sinusitis, medical treatment, 327–328 Chronic suppurative otitis media, 313 Churg-Strauss syndrome, 290 Chylomicrons, 194 Cialis. See Tadalafil Cigars, cancers related to, 1113 Ciliary body, 956f Circinate balanitis, 919f Circulatory changes, in fetus-to-newborn transition, 404 Circumcision, 419, 574–575 Cirrhosis of liver, 859–861, 860f, 1091–1092 Clarification, 1050 Classification systems for asthma, 349–352 for CHF, 509 for dementia, 971 for diabetes mellitus, 732 Gustilo–Anderson open-fracture, 602b for HIV/AIDS, 251–252 for neutropenia, 890b for peripheral neuropathies, 987 physiologic, for anemias, 882–886 for SLE, 678b for thrombocytopenic disorders, 893b Claudication, differential diagnosis, 523t–524t Clavicular complex injuries, 603–604 Clindamycin, 233t

Index Clinical assessment guidelines for children, 431–437 autism screening, 435–436 developmental screening, 433–435 development in school-age child, 436–437 evaluation of developmental delay, 435 Clinical course of HIV, 252–253 of multiple sclerosis, 998 Clinical evidence, interpreting, 115–116 Clinical features of anemia, 880–881 of delirium, 1078 of dementia, 1082–1083 of SLE, 678–680 Clinical genetics. See Genomics Clinical manifestations of elder abuse, 41 of hypopituitarism, 758–759 Clinical practice integration of psychosocial issues in, 29–30 process of motivational interviewing and, 109 Clinical presentation of acute respiratory failure, 277 of AIDS-related infections, 284–285 of aldosteronism, 782–783 of asthma, 269–270 of bronchiolitis in children, 278 of COPD, 274 of fungal infections of lung, 287 of gout, 668 of pneumonia, 279–280 of pulmonary embolism, 288 of sarcoidosis, 295 of secondary adrenal insufficiency, 780 of TB, 215, 282 Clinical problem solving finding the evidence, 125–127 focusing the question, 125 incorporating patient preferences, 127–129 making clinical decisions, 124–125 Clopidogrel, 505 Clostridium difficile diarrhea, 246, 247b Club drugs, 1128–1129 Cluster headaches, 964–965 Coagulation studies, 185 Co-analgesics for bone pain, 61–65 dosing data, 66t for neuropathic pain, 65 Cobalamin (vitamin B12) deficiency, 186 nutritional summary, 820t–824t supplements, 1147t–1154t Cobalt, nutritional summary, 820t–824t Cobb method of measuring curve severity, 647f Cocaine detection time, 1127t intoxication and withdrawal symptoms, 1130t pharmacology, 1128 street names, 1125t Coccidiomycosis, and HIV/AIDS, 251 Codeine dosing data, 62t–64t street names, 1125t

Codeine plus acetaminophen, for pain control, 61t Coenzyme Q10, 1161t, 1155t–1159t Cognitive-behavioral therapy (CBT), 1040 for fibromyalgia syndrome, 687 for substance use disorders, 1131–1132 Cognitive control, 28 Cohort studies, in HRT, 113 Coitus interruptus, 473 Colchicine, for gouty arthritis, 670 Cold injury, in sports, 587–588 Colitis, ulcerative, 866f Collagen, oral, 666–667 Collagen vascular diseases, causing FUO, 241b Collusion of anonymity, 9 Colon cancer and CEA level, 184t smoking-related, 1110 Colonoscopy, 875 Color, of urine, 900t Colorado tick fever, 231 Colorectal cancer, 77–78, 873–876 genomic applications, 1014t hereditary, 1020 Color vision, 943–944 Colposcopy, 571–572 Combination formulations with bupropion, 1120 of herbal products, 1141–1159 for hypertension, 487t–489t of insulins, 742t Combined hormonal contraceptives, 473–474 Common bile duct, obstruction, 855–856 Common cold, symptoms, 212t Common warts, 714–715 Communication basic, in interview process, 168 of data effectively to patient, 129 with dying patient, 55–57 hidden or masked, 158 listening well, 158–159 nonverbal, 149 paralanguage, 149–157 body language, 150–157 detecting lying, 157 proxemics: spatial factors, 157 touch, 150 verbal hand-on-doorknob syndrome, 148–149 vocabulary, 149 Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), 232, 592 Community-acquired pneumonia (CAP), 209t, 211t treatment, 280–281 Community resources, 163 regarding dietary change, 840 Comparative effectiveness research (CER), 121–122 Compassion, 7 Compassion fatigue, 54 Complementary and alternative medicine (CAM) for depression and anxiety, 1076 frontier science of, 144 Institute of Medicine 2005 Report, 136–137 integrating into practice, 139–144

Complementary and alternative medicine (Continued) in interview process, 170 NCCAM Strategic Plan 2010, 137–139 for obesity management, 815 in the 1990s, 133–134 in the 21st century, 134–135 terms describing, 132 for treatment of IBS, 868 White House Commission 2002 Report, 135 Complete blood count (CBC), 186–188 for HIV-infected patients, 257t Complete lens opacities, 946 Complicated grief, 65 Complicated UTIs, 921–922 Complications of diabetes, 733, 749–753 of early labor ectopic pregnancy, 375–376 molar pregnancy, 377 spontaneous abortion, 376–377 of influenza, in at-risk groups, 213b with local anesthesia, 554–555 of obesity, 808–810 of otitis media, 314–315 of parenteral nutrition, 838 pulmonary, of sickle cell disease, 290–291 of sinusitis, 325 of skin closure, 561–562 Complications of late pregnancy abruptio placentae, 380 eclampsia, 379–380 gestational hypertension, 380 HELLP syndrome, 379 intrauterine growth restriction, 378–379 placental abnormalities, 381–382 placenta previa, 380–381 preeclampsia, 379 preterm labor, 377–378 vasa previa, 381 Comprehensive medical care, 11–12 Compression fractures, thoracolumbar vertebral, 644–645 Computed tomography (CT) of chest, 265 evaluation of urinary tract, 903 of heart, 501 of nose and paranasal sinuses, 319 for PVD, 527–529 of sinuses, 328 Computed tomography (CT) colonography, 875 Concept of normal, in laboratory testing, 176–177 Concussion in sports return to play, 583–584 sideline management, 583 symptoms and incidence, 582–583 Conduct disorder, 450 Conductive hearing loss, 316b Condylomata acuminata, 715, 716f Confrontation, 1049 Congenital disorders cholesteatoma, 315 glaucoma, 932 neck masses, 339 Congenital heart disease, of newborn, 415

1141

Index Congestive heart failure (CHF), 267 ACC/AHA classification, 509 differential diagnosis, 274b pathophysiology, 508–509 pharmacologic therapy, 510–513 risk factor modification, 509–510 Conjugate meningococcal vaccine, 440 Conjugate pneumococcal vaccine, 439–440 Conjunctivitis, 346–347 allergic, 934 bacterial in adults, 933–934 in infants, 931 viral, 934 Connective tissue disorders, autoimmune, lung manifestations of, 297 Consolidation (pneumonia), 263t Conspiracy of silence, 57 Constipation, in terminally ill patient, 66–67 Consultation letter, for somatic patient, 1054 Contact dermatitis, 702–703 Contact lenses in adults, 947 overwear, 937 Contingency management, for substance use disorders, 1132 Continuing education, 5 Continuity of care, 8–9 Contraception and abnormal vaginal bleeding, 458b emergency, 477, 1102 sterilization, 476–477 use of, 468–469 Contraception methods barrier contraceptives and spermicides, 470–472 coitus interruptus/withdrawal, 473 combined hormonal contraceptives, 473–474 failure rates, 469 fertility awareness methods, 472–473 intrauterine contraceptives, 475–476 medical eligibility criteria, 469–470 progestin-only contraceptives, 474–475 Contraceptive patch, 474 Contraceptive sponge, 472 Contractions, 392–393 premature atrial (PACs), 537 Contraction stress test, in antepartum fetal surveillance, 383 Contraindications to childhood immunizations, 437–438 to cryotherapy, 563–564 to fibrinolytic therapy, 506b to herbal remedies, 1142t–1147t to mitral balloon valvuloplasty, 516b Contrasexual precocity, 788t Conversion disorder, 1028t–1029t, 1040b, 1041t–1047t, 1056 Coordination, 961 Coordinator role of family physician, 13 Copaxone. See Glatiramer Coping, 28 with crisis, 1032 styles maladaptive, 1051 of patient with somatic symptoms, 1048

1142

Copper nutritional summary, 820t–824t supplements, 1147t–1154t Copper-T380A intrauterine device, 475–477 Core beliefs, and irrational thoughts, 1040–1048 Corneal abrasion, 931f, 937 Corneal herpetic infections, 935 Corneal lacerations, 938 Corneal light reflex test, 941 Corneal ulcers, 935–936 Coronary angioplasty, 503 Coronary artery disease accompanying diabetes, 752–753 acute coronary syndromes, 503–508 and preferred contraceptive options, 470t stable angina, 499–503 Coronary heart disease, smoking as risk factor, 1111 Corticosteroids in bacterial meningitis, 978–980 effect on lipid values, 195t inhaled, for asthma, 271, 273t nasal, doses for, 323t therapeutic injection, 654 topical, prescribing, 692 Cortisol in Cushing’s syndrome, 780 serum levels in Cushing’s disease, 763 Cost-effective care, 10–11 Cough, acute and chronic, 268 Council on Graduate Medical Education (COGME), 6 Counseling 5As framework, 92–93 for children and adolescents, 91 couples, 1033–1034 on dietary changes, 838–839 effectiveness, for tobacco use, 84 on healthy diet, 90 on physical activity, 90 preconception, 361, 402–403 throughout pregnancy, 365t on use of contraception, 468–469 Counterforce brace, 620f Cover test, 941 Crab lice, 718 Cranberry, 1142t–1147t, 1161t Cranial nerve examination, 960–961 Cranial nerve involvement, neuropathies with, 990b Cranial neuropathies, 994 Cravings, nicotine, 1105–1106 C-reactive protein (CRP), 189, 497–498, 827 high-sensitivity, 521 Creatine, drug interactions, 1155t–1159t Creatinine laboratory test, 183 serum, 45 Creatinine/height ratio, 827 Creutzfeldt-Jakob disease, 1089 Crisis current understanding of, 1023 resolution, strategy for, 1032, 1034b trauma, and disaster theory, 1022–1025 Crisis evaluation acute crisis resolution, 1027 crisis state, 1026–1027

Crisis evaluation (Continued) normal equilibrium state and stressors, 1025–1026 previous psychiatric or personality disorder, 1027 selective past history, 1027–1029 sequelae of crisis, 1027 Crisis intervention basic approach, 1029–1030 ecological map, 1031 problem-focused treatment, 1031–1032 theory, 1025f timeline, 1030–1031 Critical limb ischemia, 519–520, 522 Crixivan. See Indinavir sulfate Crohn’s disease, 864, 866f–867f Cross-cultural issues gestures, 155 in interviewing, 171–172 Croup, 301t, 335 Crouzon’s syndrome, 944f Crowning, 396f Crown-rump length, 398f Crude herb formulation, 1143t Crusted scabies, 717 Crying behavior, of neonate, 419 Cryotherapy, 563–564 Cryptococcus neoformans meningitis, 259t Cryptosporidiosis, 252 Crystal arthropathies gout, 668–670 pseudogout, 670–672 Crystals, in urine, 902 Cubital tunnel syndrome, 990–991 Cultural competency, 171–172 Culture for chronic meningitis, 984b urine, 902 CURB-65, 210 Curettage, endocervical, 572 Curing, and primary medical home, 17–20 Cushing’s disease, 762–763 Cushing’s syndrome, 780–781 and obesity, 808 Cutaneous abscess, incision and drainage, 564–565 Cutaneous sarcoidosis, 722f Cutoff value, of laboratory test, 178 Cyanosis, in neonate, 412 Cyclosporine effect on lipid values, 195t for rheumatoid arthritis, 665 Cystic fibrosis, 278, 1020–1021 Cystitis acute uncomplicated, 226t interstitial, 917 uncomplicated, 921 Cystoscopy, 902–903 Cysts Bartholin’s gland, 571 breast, aspiration, 574 epidermal inclusion, 724 lymphoepithelial, 341 midline neck masses, 339 ovarian, 459–460, 464 thyroid, 773–774 Cytokines, production abnormalities, 344t Cytolytic vaginitis, 463

Index Cytomegalovirus (CMV), 214–215 and HIV/AIDS, 251 in pregnancy, 370 retinitis, 259t

D Dacryocystitis acute, 931 chronic, 932 Dandelion, 1142t–1147t Daptomycin, 233t Darifenacin, 51t Darunavir, 258t Darvocet. See Propoxyphene Darvon. See Propoxyphene DASH diet, 831 Data, psychosocial, 29 Daytrana skin patch. See Methylphenidate Debridement, 555 for pressure ulcers, 44 Decelerations, FHR, 391–392, 394f Decisional control, 28 Decision making clinical problem solving and, 124–125 nutritional, for hospitalized patient, 835–838 point-of-care, organizing information for, 122 shared, 127–128 Decoction, herbal, 1143t Decongestants, exposure in pregnancy, 369t Deep tendon reflexes (DTRs), 961 Deep vein thrombosis (DVT), 267 Defense mechanisms maladaptive, 1051 of patient with somatic symptoms, 1048 Defensive body position, 155f–156f Defibrillators for arrhythmias, 545–549 and cardiac resynchronization, 548–549 Degenerative osteoarthritis, of knee, 616–618 Dehydration, pediatric, 844–846 Dehydroepiandrosterone (DHEA), 777, 1155t–1159t Delavirdine mesylate, 258t Delayed puberty, 787–789 Delayed sleep-phase syndrome, 445 Delayed-type hypersensitivity (DTH), 216–217 Delirium clinical features, 1078 diagnostic process, 1079–1081 etiology, 1079 evaluation for, 970–971 natural history of, 1082 presenting characteristics, 1083t prevention, 1081 treatment, 1081–1082 Delirium tremens, 1096–1097 Delivering bad news, 56–57, 174 Dementia behavioral and psychiatric symptoms accompanying, 1089 care settings for patient, 1089–1090 classification and pathophysiology, 971 clinical features, 1082–1083 as concern in interview process, 174 diagnostic process, 1083–1084

Dementia (Continued) evaluation, 971–972 with Lewy bodies, 995, 1088b management, 972 pharmacotherapy, 972–973 types, 1084–1088 Demerol. See Meperidine Demographics of obesity, 805–806 Denial, of patient’s own impending death, 57–58 Dependence, substance, 1124b Dependent personality disorder, 1041t–1047t, 1057–1058 Depot medroxyprogesterone acetate (DMPA), 475 Depression antidepressant failure, 1073 antidepressants and suicidal ideation, 1075–1076 assessment of depressed patient in medical settings, 1067–1069 CAM for, 1076 differential diagnosis, 1068 disease course, 1061 drug therapy, 65 ECT and VNS for, 1076 epidemiology, 1060–1061 genomic applications, 1014t Geriatric Depression Scale, 35 health care costs related to, 1061 interaction with anxiety, 1062 medical illness interaction with, 1062–1063 medication selection, 1069–1072 mood disorders diagnosis, 1063–1066 neurobiology and genetics, 1061–1062 in Parkinson’s disease, 997 preventive services, 85–86 psychotherapy for, 1077 screening tools for, 1065 smoking as risk factor, 1112 suicide screening and assessment, 1068–1069 treatment discontinuation, 1072–1073 unipolar vs. bipolar, 1064–1065 DeQuervain’s tenosynovitis, 613–614 Dermacentor andersoni tick, 231f Dermatitis atopic, 693–694 contact, 702–703 generalized exfoliative, 704–705 nummular, 704 stasis, 704 Dermatitis herpetiformis, 873 Dermatofibroma, 724, 725f Dermatology benign growths, 723–724 childhood skin problems, 693–697 drug eruptions, 718–720 general management, 692–693 infectious skin diseases bacterial, 705–707 fungal, 708–713 viral, 713–716 infestations, 716–718 inflammatory dermatologic diseases, 698–705 premalignant and malignant skin lesions, 724–730

Dermatology (Continued) principles of diagnosis, 690–692 skin signs of systemic disease, 720–723 sports, 591–592 Dermatome patterns, of forearm, 635f Dermatomyositis, 722 Dermatophytosis (tinea), 708 Dermoid cysts, 339 Desmopressin, 764 Desoxyn. See Methamphetamine Desquamative inflammatory vaginitis, 463 Detachment, of anterior inferior labrum, 610f Detoxification, alcohol, 1095–1097 Detrol. See Tolterodine Developmental delay, evaluation of, 435, 436t Developmental dysplasia of hip, in newborn, 409 Developmental milestones, in young children, 434t–435t Developmental screening, in young children, 433–435 Developmental theories, 431, 432t Deviated septum, 322 Dexamethasone suppression test (DST), 780–781 Dexedrine. See Dextroamphetamine Dexmethylphenidate, 449t Dextroamphetamine, 449t Dextromethorphan, 1125t Diabetes insipidus, 764–765 Diabetes mellitus cardiovascular effects, 495 classification and diagnosis, 732 definition, 731–732 diabetic complications, 749–753 diabetic ketoacidosis, 744–747 epidemiology, 732–733 gestational, 374–375 hospital care of diabetic patients, 748–749 improvement of diabetic outcomes, 754–755 maternal, infants of, 415–416 metabolic syndrome, 753–754 pathogenesis, 731–732 pathophysiology, 732 and preferred contraceptive options, 470t and pregnancy, 747–748 presentation, 735–736 risk factor for PVD, 520 stroke, 967 smoking as risk factor, 1112 type1. See Type 1 diabetes mellitus type2. See Type 2 diabetes mellitus Diabetes mellitus management, 495–497 behavioral therapy, 736 diet, 834–835 exercise, 737–738 glucose monitoring, 736–737 insulins, 741–744 nutrition and diet, 737 pharmacologic therapies, 739–741 surgery as therapy, 744 Diabetic ketoacidosis, 744–747 Diabetic macroangiopathy, 752 Diabetic neuropathy, 750, 992–993 Diabetic retinopathy, 750, 953–954 Diabetic ulcers, 234–235

1143

Index Diagnosis of acute respiratory failure, 277 of AIDS-related infections, 285 of anaphylaxis, 354b of anxiety disorders, 1066–1067 of asthma, 269–270 of COPD, 274–275 of delirium, 1079–1081 of dementia, 1083–1084 of diabetes mellitus, 732 of diseases of pleura and extrapulmonary space, 297–298 of ectopic pregnancy, 375 of HIV, 253–254 of interstitial lung diseases, 296 of lung cancer, 291 of mood disorders, 1063–1066 of multiple sclerosis, 997–998 of pulmonary embolism, 288 of sarcoidosis, 295 of sickle cell anemia, 886–887 of spontaneous abortion, 376 of TB, 216, 282–283 of thyroid function, 769f Diagnostic and Statistical Manual of Mental Disorders, 4th ed., revised (DSM-IV-TR) ADHD, 447b delirium, 1079b personality disorders, 1041t–1043t substance abuse and dependence, 1124b Diagnostic skills, of family physician, 12–13 Diagnostic tests for aortic stenosis, 513 to exclude or confirm pulmonary embolism, 289t genetic, prenatal, 367–368 for herniated disk, 642 for pneumonia, 209–210 for thoracolumbar conditions, 637 Diagnostic ultrasound, 396–397 Dial test, 623f Diaphragm, 471–472, 569 Diaries, voiding (bladder), 50 Diarrhea infectious, 244–246 pediatric, 844–846 Diastolic dysfunction, pharmacologic therapy, 510 Dicloxacillin, 233t Dicyclomine, in elderly, 46t Didanosine, 258t Diet anti-inflammatory, 141t for diabetes mellitus, 737 elimination diets, 668b gluten-free, 873 healthy, counseling on, 90 heart healthy measures, 104f improvement through behavioral modifications, 838–840 for obese patients, 812–814 in prevention and management of major disease, 831–835 protecting against gene changes in smokers, 1121 varied, for healthy children, 430 Dietary allowances, for women, 363t Dietary guidance system, 818–819

1144

Dietary history, 824–825 Dietary recommendations for diabetes mellitus, 737 for therapeutic lifestyle change, 482t Dietary supplements combination products, 1141–1159 herbal remedies, 1141, 1142t–1147t nutraceuticals, 1141 safety of, 1136–1140 trends in supplement use, 1135–1136 types of, 1140–1159 and vascular disease, 833–834 vitamins and minerals, 830t, 1141, 1147t–1154t Dieting, normal, vs. eating disorders, 453t Differential diagnosis for abdominal pain based on location, 845b of anaphylaxis, 355b for anxiety disorders, 1068 of asthma, 348b of claudication, 523t–524t concerning signs and symptoms in newborn, 413–415 of COPD, 274b of depression, 1068 of dysuria, 903b for fever of unknown origin, 240 of hypercalcemia, 797b of Parkinson’s disease, 995 of pelvic mass, 460t of red eye, 929t of vaginal discharge, 461b Difficult patients with diabetes, 744 in interview process, 169, 174 schema for managing, 1041t–1043t with somatization consultation letter, 1054 management algorithm, 1053–1054 parallel diagnostic inquiry, 1052–1053 psychotherapy for, 1054 Difficult patients: management principles accepting patient’s limitations and strengths, 1050–1051 attending to problematic alliance, 1049 basic psychotherapy techniques, 1049–1050 choosing focus for interview, 1049 discussing defense mechanisms and coping, 1051 emotional needs of patient, 1050 empathizing with patient’s worldview, 1050 environmental support, 1050 improving capacity to test reality, 1050 managing unreasonable expectations, 1051 prescribing medication, 1051–1052 questioning illogical feelings, 1051 Diffuse panbronchiolitis, 274b Diffusion capacity, 264 Digestion, 819 Digital block, 554 Digital flexor tenosynovitis, 614 Digital nerve anatomy, 555f Digital rectal examination (DRE), 197, 874 Digits, surgery of, 565–566 Digoxin, in elderly, 46t Dihydropyridines, 487t–489t 1,25-Dihydroxyvitamin D, 204

Dilaudid. See Hydromorphone Dipeptidyl peptidase inhibitors, 741 Diphtheria, tetanus toxoids, and acellular pertussis vaccines (DTaP), 438–439 Dipstick urinalysis, 900–901 Dipyridamole, in elderly, 46t Directly observed therapy (DOT), for TB, 283 Disaster, development of crisis, trauma, disaster theory, 1022–1025 Disaster evaluation adaptation to crisis, 1027 crisis state, 1026–1027 normal equilibrium and stressors, 1025–1026 previous psychiatric or personality disorder, 1027 selective past history, 1027–1029 sequelae of disaster, 1027 social systems, 1029 Discipline, of children, 427–428 Discoid LE, 721 Discontinuation of antidepressant treatment, 1072–1073 Disease. See also Burden of disease; Illness classification, laboratory test’s cutoff value, 178f expressing burden of, 76 relationship to smoking, 1107b treatment, balancing with promotion of health, 18 Disease-modifying antirheumatic drugs (DMARDs), 662–663 Disease-modifying therapies, for multiple sclerosis, 998–999 Disease-specific mortality, change in, 102t Disequilibrium, 985t Disk degeneration, 634–635 Dislocations, sternoclavicular joint, 604 Disopyramide, in elderly, 46t Dissatisfaction, patient, 148 Dissociative disorders, 1028t–1029t Distal radius fractures, 615–616 Distal symmetric polyneuropathies, 989b Disulfiram, 1100 Ditropan. See Oxybutynin Diuretics for hypertension, 487t–489t loop, 184t thiazide, effect on lipid values, 195t Diverticular disease, 870–872 Diverticulosis, 871f Dizziness conditions associated with, 985–986 evaluation, 984–985 history of, 306b Documentation of cases of intimate partner violence, 1034–1035 of elder abuse, 41 Domestic abuse, treatment of intimate batterers, 1033 Dong quai, 1142t–1147t Do not resuscitate order, 70 Donovan bodies, 222f Dopamine, 996–667 Dopamine agonists, 996t Doppler ultrasound, for PVD, 527

Index Dosing data for antidepressants and antianxiety agents, 1068t for antiepileptics, 976t for antimicrobial therapy, 981t for co-analgesics, 66t for nicotine patch, 1120t for opioids, 62t–64t for Parkinson’s disease medications, 996t Double-contrast barium enema (DCBE), 874 Down syndrome, second trimester screen results, 368t Doxepin, in elderly, 46t Doxycycline, 233t Drainage of cutaneous abscess, 564–565 of paronychia, 566f Dressings for pressure ulcers, 44, 45t wound, 558 Drug abuse intoxication and withdrawal, 1129–1130 laboratory testing, 1127 medical management, 1130–1131 pharmacology, 1128–1129 scope of problem, 1123–1125 screening, 1125–1127 special populations, 1133 Drug eruptions, 718–720 erythema multiforme, 719–720 morbilliform reaction, 719 Stevens-Johnson syndrome, 720 toxic epidermal necrolysis, 720 urticaria, 719 Drug-induced conditions abnormal potassium, 198t calcium abnormalities, 184t delirium, 1081b FUO, 241b hyperuricemia, 201t hypomagnesemia, 196t immune-mediated platelet destruction, 894 lupus, 679 parkinsonism, 995 SIADH, 765b Drug interactions with herbal remedies, 1142t–1147t with nutraceuticals, 1155t–1159t Drugs. See also Medications; specific drug classes club, 1128–1129 effect on lipid values, 195t thyroid function and testing, 775 exposures in pregnancy, 368–369 to limit or avoid in elderly population, 46t street names, 1125t urine drug screens, 203–204 Dry eye, 949–950 Dry herb formulation, 1143t Dry mouth, with Sjögren’s syndrome, 682 Dual-chamber pacemaker, 547f Dual diagnosis, alcohol dependency and psychiatric comorbidities, 1099–1100 Dumping syndrome, 816 Durable power of attorney, 70 Duragesic patch. See Fentanyl

Dying patient: care of advance directives, 69–71 American attitudes toward dying, 53 communication, 55–57 denial, 57–58 hospice care, 68–69 importance of hope, 59 management of symptoms, 59–67 nutrition, 67–68 patient control, 58–59 physician attitudes, 54–55 protraction of dying process, 59 treatment and the right time to die, 54–55 watch with me, 58 where to die, 68 Dysesthesia, co-analgesics for, 66t Dysfunctional labor, 387–388 Dysfunctional voiding, 914 Dyshidrotic eczema, 703–704 Dyslipidemia, 479–486, 736 complication of obesity, 808 Dyspareunia female, 1004–1005 male, 1008 Dyspepsia, 848 Dysphagia, oropharyngeal, 332 Dysplasia, of hips in newborn, 409 Dysplastic nevi, 562, 695f Dyspnea acute, BNP testing, 196 drug therapy, 65–66 Dysproteinemic neuropathies, 993 Dysthymia, 1063–1064 Dysthymic disorder, diagnostic criteria, 1064b Dystocia, shoulder, 388–389 Dysuria, 903–904

E Ear(s) disorders of external ear, 309–311 middle ear, 311–315 hearing loss, 315–318 otalgia, 305–306 tinnitus, 308–309 tumors, 306 vertigo, 306–308 Eating disorders, 452 Eating skills summary, 829f Echinacea, 1142t–1147t Echocardiography, stress, 501 Eclampsia, 379–380 Ecological map of support network, 1031 Ectoparasites, 225 Ectopic atrial rhythm, 537–538 Ectopic pregnancy, 375–376 Eczema, 693–694 dyshidrotic, 703–704 Edema cerebral, in stroke, 969 high-altitude, 588 Education level, and obesity, 805–806 Efavirenz (EFV), 258t Effient. See Prasugrel

Effusion otitis media with, 313–314 pleural, 263t synovial, 653f Ehrlichiosis, 228–230 Ejaculation, premature, 915, 1007–1008 Elbow, olecranon bursitis, 611–612 Elbow tendinopathy lateral, 610–611 medial, 611 Elderberry, 1142t–1147t Elderly patients. See also Older adults in clinical interview, 173–174 differential diagnosis of FUO, 241b elder abuse, 39–42 falls, 36–38 geriatric assessment, 33–36 pressure ulcers, 42–45 preventive services for, 92 rational drug prescribing for, 45–47 urinary incontinence, 47–52 Electrocardiogram (ECG), 267 for stable angina, 499 surface, 534 Electroconvulsive therapy (ECT), for depression, 1076 Electromyography, 988 Electronic cigarettes, 1113 Electronic fetal monitoring contractions, 392–393 interpretation of FHR recordings, 389–392 Electronic health record (EHR), 120–121 managing patient relationships, 121 Electrophysiology study, for arrhythmia, 544–545 Eleuthero, 1142t–1147t Elevated blood pressure, in stroke, 969 Elimination diet, for rheumatoid arthritis, 668b Elimination habits, of neonate, 418 Emergencies contraception, 477, 1102 hypertensive, 491t ocular, 936 otorhinolaryngological, 300–305, 320 Emergency department, initial management of stroke, 968 EMLA dosing, 553t Emotional abuse, of elderly, 41t Emotional needs of patient, 1050 Emotional support, 26 Emotions, chronic negative, 26 Empowerment, in primary medical home, 20 Empty can test, 606 Empty sella syndrome, 758 Emtricitabine, 258t Emtriva. See Emtricitabine Enablex. See Darifenacin Encephalitis Toxoplasma gondii, 259t viral, 244 Endocarditis, prevention of, 518 Endocervical curettage, 572 Endocrinology adrenal glands, 777–784 calcium and phosphate disturbances, 796–800 endocrine factors for obesity, 807–808

1145

Index Endocrinology (Continued) ovarian and testicular disorders, 784–796 pituitary disorders, 756–767 preventive services for endocrine conditions, 88–90 thyroid disorders, 767–777 End-of-life discussions, 55 concerning Alzheimer’s patients, 1087 religious and spiritual, 59 Endometrial biopsy, 572–573 Endoscopic cautery, for epistaxis, 304–305 Endoscopic retrograde cholangiopancreatography (ERCP), 858f Endoscopy capsule, 875–876 urinary, 902–903 Energy density of foods, 813–814 Energy medicine, 144 Enfuvirtide, 258t Engel, George, 25 Enhanced external counterpulsation (EECP), 503 Enteral nutrition, 838 Enteroclysis, 869–870 Enteropathic arthropathy, 675 Enuresis, 914 Environmental equilibrium, 1025 Environmental influences, in sports medicine, 586–588 Enzymatic debridement, for pressure ulcers, 44 Enzyme-linked immunosorbent assay (ELISA), 193 Eosinophilia, 891–892 Epicondylitis lateral, 610 medial, 611 Epidemiology of AIDS-related infections, 284 of anxiety and depressive disorders, 1060–1061 of asthma, 269 of COPD, 273–274 of diabetes mellitus, 732–733 of falls in elderly patients, 36–38 of fungal infections of lung, 287 of gastrointestinal disease, 843–844 of HIV, 248–249 of interstitial lung diseases, 296 of lung cancer, 291 of pulmonary embolism, 288–289 of pulmonary hypertension, 289–290 of PVD, 518–519 of rheumatoid arthritis, 659 of TB, 215 Epididymitis, 919 Epiglottitis, 300–301 Epinephrine, in anaphylaxis, 355 Episiotomy, 396 Epistaxis, 320 in sports facial trauma, 589 treatment, 303–305 Epivir. See Lamivudine Epstein-Barr virus (EBV), 214–215 laboratory test, 195–196 pharyngitis caused by, 331–332 Equipment for cryotherapy, 564 for neonatal resuscitation, 404b

1146

Equipment (Continued) for office procedure room, 552–553 for therapy of anaphylaxis, 356b Erectile dysfunction (ED), 914–915 evaluation, 1005–1006 treatment, 1006–1007 Ergocalciferol, supplements, 1147t–1154t Erikson, Erik, 1023 Erikson’s psychosocial stages, 432t Erysipelas (St. Anthony’s fire), 706 Erythema infectiosum, 697 Erythema migrans rash, 676 Erythema multiforme, 719–720 Erythema nodosum, 705 Erythrasma, 707 Erythrocyte sedimentation rate (ESR), 189–190 Erythrocytosis. See Polycythemia Erythroderma, secondary to pustular psoriasis, 704f Erythrodermic psoriasis, 698 Erythromycin, 233t Erythroplasia of Queyrat, 725–726 Erythropoietin (EPO), 878–879 inadequate production, 882 Esophageal adenocarcinoma, 847–855 Esophageal cancer, smoking-related, 1109 Esophagitis, 852f Esophagus Barrett’s, 847–855, 848f foreign bodies in, 302 motor disorders of, 332 Esotropia, accommodative, 943f Essential oil, herbal formulation, 1143t Essential thrombosis, 888 Establishing rapport communication hidden, 158 nonverbal, 149 paralanguage, 149–157 verbal, 148–149 eye contact and, 146 listening well, 158–159 patient satisfaction and, 147–148 respect, 147 Esters, 551b Estimated average requirement (EAR), 841 Estimated energy requirement (EER), 841 Estriols, 368t Estrogens for incontinence, 51t oral, effect on lipid values, 195t Etanercept, for rheumatoid arthritis, 665 Ethical issues, in genetic testing, 1018 Ethnicity chronic disease and, 34 and obesity, 805 Ethnomedical cultural model, 28–29 Ethylenediamine-tetraacetic acid (EDTA), 1155t–1159t Etravirine, 258t European Prospective Investigation into Cancer and Nutrition, 105, 106t–107t Euvolemic hyponatremia, 200t, 201 Evening primrose, 1142t–1147t Evidence-based medicine distinguishing characteristics, 116t genetics and, 1014 published research and, 112–113

Evidence-based practice, 30–31 Evidence-based prevention challenges in, 75–76 definitions, 74 key concepts, 73–76 preventive services task force and, 74–75 Evidence pyramid, 126f Exanthemlike reaction, 719 Excisions atypical moles and pigmented lesions, 562–563 basal cell cancer, 563 Exenatide, 741 Exercise for diabetes mellitus, 737 healthy lifestyle and, 103 for low back pain, 640–641 for obesity, 814 in pregnancy, 364b for PVD, 529 Exercise-induced bronchospasm, 353, 592–593 Exercise prescription, for diabetes mellitus, 738 Exercise treadmill stress testing, 499–500 Exertional heat illness, 587t in sports, 586 Exertional hemolysis, 593 Exertional hyponatremia, 586–587 Exfoliative dermatitis, generalized, 704–705 Exocrine pancreas, disorders of, 734 Exotropia, 944f Expectations of patient, 158 unreasonable, of difficult patient, 1051 Expiratory grunting, in neonate, 412 Exploitation, of elderly, 41t Exposure keratitis, 950 Extensor mechanism problems, 618 External ear disorders auricular hematoma, 309–310 cerumen, 310–311 external auditory canal foreign bodies, 310 frostbite, 311 lacerations, 311 otitis externa, 309 External hemorrhoids, 567–568 Extraocular rotations test, 941–942 Extrapulmonary space diseases, 297–298 Extrarenal macrovascular disease, in diabetes, 753 Extravascular hemolysis, 885–886 Extrinsic risk factors, for pressure ulcers, 42–43 Exudative phase of healing, 556 Eyeball, anatomy of, 929f Eyebright, 1142t–1147t Eye contact, 146 Eyelid, diseases of, 948 Eye(s) allergy in, 346–347 in body language, 153–154 injuries, 937–938 movements, in neurolinguistic programming, 157f of newborn, 408 sports trauma to, 588–590 thyroid eye disease, 950 Ezetimibe, 483

Index

F Face in body language, 152 of newborn, 408 sports trauma to, 588–590 Facial nerve (CN VII) examination, 960 paralysis, 318–319 idiopathic acute peripheral, 994 Facilitation of patient education, 161 Factitious disorder, 1040b, 1041t–1047t, 1055 Failure rates, of contraception methods, 469, 471t Falls, in elderly, 36–39 False-positive treatment, of dying patient, 54 Famciclovir, for HSV infection, 220t Familial adenomatous polyposis, 874b Familial short stature, and constitutional growth delay, 423–424 Family, support for, 69 Family history, guide to genetic disease, 1014–1015 Family medicine care of children, 421–422 definition, 5 and shared decision making, 128 Family physician approach to patient with HIV, 254–255 attributes of, 8t characteristics and functions of, 7–13 decision support, 122 definition, 5 development of specialty, 4–5 electronic medical record, 15 family practice, 4 patient-centered medical home, 15 personalized care, 6–7 in practice, 14–15 prevention and, 74 professional development, 123 role in systems change, 94 universal screening for alcoholism, 1104 Family practice crisis intervention in office setting basic approach, 1029–1030 ecological map, 1031 symptom-oriented treatment, 1031–1032 timeline, 1030–1031 planning for patient education in, 163–165 Fantasies, in physician–difficult patient encounter, 1048–1049 Fasting plasma glucose level, 191 Fat dietary intake, in diabetes, 834–835 nutritional summary, 820t–824t Fatty acids absorption, 825t effect on inflammation, 651f Fatty liver disease, obesity and, 810 Fears, core beliefs and, 1040–1048 Febrile neutropenia, 891b Febrile seizures, 973–974 Fecal immunochemical test (FIT), 874 Fecal occult blood test (FOBT), 190–191 Feedback, in patient education, 161

Feeding nasogastric, 838 by neonate parental education on, 418 refusal, 412 Feeding disorders, in infancy, 452 Feelings associated with trauma, 1024b illogical, of difficult patient, 1051 Feet, gout in, 669f Feldenkrais, 143t Felty’s syndrome, 890–891 Female athletes, special concerns for, 598–600 Female condom, 471 Female infertility, 793–794 Female sexual dysfunction female sexual arousal disorder, 1003 hypoactive sexual desire disorder, 1002–1003 orgasmic disorder, 1003–1004 sexual pain disorders, 1004–1005 Femoral nerve stretch test, 638f Femoral neuropathy, 991 Femoral pulses, absence in neonate, 413 Fentanyl, 61 dosing data, 62t–64t Ferritin, low, in nonanemic athlete, 593 Ferrous sulfate, in elderly, 46t Fertility awareness methods, 472–473 Fetal fibronectin, 377 Fetal heart rate (FHR) interpretation of recordings, 389–392 sinusoidal pattern, 395f Fetal hydronephrosis, 910 Fetal surveillance, antepartum, 382–384 α-Fetoprotein, 368t Fetus-to-newborn transition, 403–406 Fever rheumatic, 677–678 in stroke, 970 Feverfew, 1142t–1147t Fever of unknown origin (FUO), 240–242 Fiber dietary, 833 for type 1 diabetes, 834 Fibrates, 484 Fibrinogen, and PVD, 521 Fibrinolytic therapy, contraindication to, 506b Fibroblast growth factor (FGF), 556f Fibroids, uterine, 459 Fibromyalgia syndrome, 685 FICA mnemonic, 141t Filiform warts, 714–715 Filling thrombus, at occlusion site, 506f Filtered cigarettes, 1113 Fine-needle aspiration biopsy (FNAB) for breast mass, 574 for evaluating thyroid masses, 769 for thyroid nodules, 342 First-degree AV block, 540 First stage of labor, 384 Fish oil for dyslipidemia, 484–485 recommended use of, 139 Fistula, perilymph, 308 Five “As” intervention technique, 1126b Five-factor model of personality, 26t Flank pain, 904

Flexible sigmoidoscopy, 874–875 Flexion, measuring, 637f Flexor tendon nodule, 614f Floaters, vitreous, 951 Flomax. See Tamsulosin Fluid extract, herbal formulation, 1143t Flunitrazepam pharmacology, 1129 street names, 1125t Fluoride, nutritional summary, 820t–824t Fluoroscopy, airway, 334 Focalin. See Dexmethylphenidate Folic acid deficiency, 186, 883 nutritional summary, 820t–824t supplements, 1147t–1154t Folliculitis, 707 Food pyramids Healing Foods Pyramid, 140f MyPyramid food guidance system, 818 U.S. government, 139 Foods causing anaphylaxis, 355b Foot infection, diabetic evaluation and treatment algorithm, 236f osteomyelitis, 239 Forced vital capacity (FVC), 264 in COPD, 275–276 Forceps delivery, 398 Forearm, dermatome patterns, 635f Foreign bodies in airway, 302–303 in esophagus, 302 external auditory canal, 310 in nose, 321 ocular, 937–938 Fosamprenavir calcium, 258t Fourth stage of labor, 386 Fractures clavicular, 603 distal radius, 615–616 growth plate, 601–603 metatarsal, 629 Salter–Harris, 602–603 scaphoid, 616 stress, 597 thoracolumbar vertebral compression, 644–645 Francisella tularensis, 230–231 Free-dried herbal extract, 1143t Free fatty acids, 492–493 Frontotemporal lobar degenerations, 1088 Frostbite of external ear, 311 in sports, 587–588 Fructo-oligosaccharides, 1155t–1159t Functional assessment of elderly patients, 35 of rheumatic diseases, 653–654 Functional incontinence, 49 Fundal growth, 366f Fungal infections AIDS-defining illnesses, 251–252 of lung, 287 in sports medicine, 591 Fungal skin infections dermatophytosis, 708 onychomycosis, 711 tinea capitis, 710–711

1147

Index Fungal skin infections (Continued) tinea corporis, 708 tinea cruris, 710 tinea pedis, 708–710 tinea versicolor, 711–713 Fungi, in urine, 902 Furuncles, 232–234, 707 Fuzeon. See Enfuvirtide

G Gait, 961 Gallbladder disease cholelithiasis and cholecystitis, 855–856 obesity and, 810 Gallium scan, for AIDS-related infections, 285 Gallstones, 856f–857f Garlic, 1142t–1147t Gastric band for obesity, 816f Gastric ulcer, 849f Gastroenteritis, viral, 245–246 Gastroesophageal reflux disease (GERD), 851–852 Gastrointestinal (GI) disease abdominal examination, 844 adult disorders esophagus, 847–848 stomach and duodenum, 848–855 gallbladder, 855–856 liver, 856–861 lower GI tract, 863–876 pancreas, 861–863 pediatric disorders appendicitis, 846–847 diarrhea and dehydration, 844–846 infantile regurgitation, 844 psychosocial factors of, 843–844 Gastrointestinal (GI) system absorption of lipid and cholesterol, 483f causes of chronic pelvic pain, 465b problems in athletes, 594 symptoms associated with trauma, 1024b Gastroparesis, 855 Gay patients, 1008 Gender differences effect on ESR, 190t in lung cancer death rates, 1109f for obesity, 805 and risk for PVD, 520 for top 15 cancer sites, 78t Gender identity and expression, 1008–1009 General appearance of newborn, 407 Generalized anxiety disorder (GAD), 1028t–1029t, 1060 diagnostic criteria, 1066b disease course, 1061 interaction with medical illness, 1062 pharmacologic therapies for, 1073–1075 Genetic factors in anxiety and depression, 1061–1062 for arthritides, 651 for diabetes, 733 in IBD, 864 for obesity, 806 Genetic screening counseling, 362b Genetic testing, 1015–1018 for addiction to nicotine, 1121 direct-to-consumer testing, 1017–1018

1148

Genetic testing (Continued) pharmacogenetics, 1017 prenatal diagnostic, 367–368, 1016–1017 Genitalia male, sexual maturity stages, 425t of newborn, 408–409 Genital ulcers chancroid, 222 herpes simplex, 219–220 LGV and granuloma inguinale, 222 syphilis, 220–221 Genital warts, 225t, 715 Genitourinary infections, 225–227 prostatitis, 227–228 UTIs, 226–227 Genomics and diet, 840–841 ethical, legal, and social issues, 1018 evidence-based medicine, 1014 family history and, 1014–1015 genetics vs., 1013 in primary care practice, 1018–1021 Geriatric assessment functional assessment, 35 key points of, 33 medical assessment, 34–35 psychological assessment, 35 social assessment, 35–36 Geriatric Depression Scale, 35 Geriatric health questionnaire, 37f Gestational age, postnatal assessment, 410 Gestational diabetes mellitus, 374–375 diagnosis, 732 postpartum, 748 screening, 747 Gestational hypertension, 380 Gestational trophoblastic disease, 377 Gestures, in body language, 155 Giant cell arteritis, 683, 954–955 Gilbert’s syndrome, 182–183 Ginger, 1161t, 1142t–1147t Gingko biloba, 1086, 1142t–1147t Ginseng, 1142t–1147t Glanzmann thrombasthenia, 895 Glatiramer, 999 Glaucoma angle-closure, 936 congenital, 932 medications, 948 open-angle, 955 optic nerve damage with, 955–956 Gliptins, 741 Glitazones, 741, 747 Global cardiac risk, 101–103 Globus hystericus, 332 Glomerular disease, in children, 909b Glomerular filtration rate (GFR), 183 Glomerulopathy, diabetic, 751 Glossopharyngeal nerve (CN IX), 960 Glucocorticoids excess of, 763 intra-articular, 658 intranasal, 345 for rheumatoid arthritis, 666 Glucosamine and chondroitin, 658, 1155t–1159t Glucosamine sulfate, 1161t

Glucose laboratory test, 191–192 monitoring, for diabetes mellitus, 736–737 in urine, 901 Glucose-6-phosphate dehydrogenase deficiency, 885 Glucose tolerance test (GTT), 191 α-Glucosidase inhibitors, 740 Glutamine, 1155t–1159t γ-Glutamyltransferase (GGT), 180, 1093 Gluten-free diet, 873 Glyburide, 747 Glycemic control, 88 antidiabetic drugs, 739 Glycosylated hemoglobin (Hb A1C), 192 Goal setting, for obesity management, 812 Goals of medical home empowerment, 20 establishing optimal healing environment, 18–19 healing and curing, 17–18 importance of self-care, 19 relationship centered, 19–20 treatment of disease and promotion of health, 18 Goiter, 773 nontoxic multinodular, 341–342 Gold compounds, for rheumatoid arthritis, 664t–665t Gomco clamp, 575 Gonococcal arthritis, acute, 675–676 Gonorrheal infection, 920 preventive services, 87 screening, 219t Goodpasture’s syndrome, 290 Gotu kola, 1142t–1147t Gout, 203 clinical stages, 668 recurrent, 670 Gradual disclosure, 56 Granuloma, pyogenic, 723–724 Granuloma annulare, 705, 705f Granuloma inguinale, 222 Granulomatous diseases, 184t sarcoidosis, 294–295 Grape seed, 1142t–1147t Graves disease, 342, 769–770 smoking as risk factor, 1112 Green tea, 1142t–1147t Grief, unresolved, 65 Group A beta-hemolytic streptococci (GABHS), 201 pharyngitis caused by, 330–331 Group B streptococcal sepsis, in newborn, 413, 414f Growth abnormalities, in children, 422b Growth charts, 423 Growth delay, constitutional, 423–424 Growth factors myeloid, 891 in wound healing, 557f Growth hormone deficiency, 760, 808 provocative tests for, 759–760 Growth plate fractures, 601–603 Guaiac-based FOBT, 190–191 Guaifenesin, exposure in pregnancy, 369t Guarana, 1142t–1147t

Index Guillain-Barré syndrome, 992 Gum, nicotine, 1119b, 1120 Gummas, 220 Gustilo–Anderson open-fracture classification, 602b Guttate psoriasis, 698, 699f Gynecologic causes of chronic pelvic pain, 465b Gynecologic office procedures Bartholin’s gland abscess, 571 breast cyst aspiration, 574 breast mass, 573 cervical biopsy, 572 cervical polyp removal, 573 colposcopy, 571–572 contraceptive devices, 569–571 endocervical curettage, 572 endometrial biopsy, 572–573 FNA cytology or biopsy, 574 paracervical block, 569–574 uterine aspiration, 573 Gynecology. See also Obstetrics; Pregnancy abnormal vaginal bleeding, 456–459 menopause, 466 pelvic mass, 459–460 pelvic pain acute, 464–466 chronic, 464–466 vaginal discharge, 460–463 vulvar lesions, 463–464 well-woman examination, 455–456 Gynecomastia, 786, 790 pathologic, causes of, 791t–792t

H Haemophilus ducreyi, 222 Haemophilus influenzae type b (Hib) conjugate vaccine, 438 Half-buried mattress sutures, 561 Hallucinogens, pharmacology, 1128 Hallucinosis, alcoholic, 1095 Hand, foot, and mouth disease, 697 Hand-on-the-doorknob syndrome, 148–149 Hands, in body language, 154–155 Handshake, politician’s, 150f Hardiness, 25–26 Hashimoto’s thyroiditis, 771–772 Hatha yoga, 143t Hawkins test, 608f Hawthorn, 1161t, 1142t–1147t Head, of newborn, 408 Headaches cluster, 964–965 medication-overuse, 965 migraine, 962–964 in older adults, 965 paroxysmal hemicrania, 965 and pediatric ophthalmology, 944–945 tension-type, 964 Head and neck cancer, smoking-related, 1109 Head and neck trauma, 305 Head lice, 717–718 Head position, in body language, 152 Head tilt, 944f Healing, and primary medical home, 17–20 Health belief model, 94t

Health care preventive. See Preventive health care for transgender individuals, 1009 utilization, by difficult patients, 1044t–1047t Health care surrogate, 70 Health care system costs and cost-effective care, 10–11 related to anxiety and depression, 1061 public-owned, 20 Health effects, of intimate partner violence, 1024–1025 Health information exchange, 123 Health literacy, 164 Health Professionals Follow-up Study, 105, 106t–107t Health promotion, throughout pregnancy, 365t Health risks with smoking cancer, 1106–1110 cardiovascular disease, 1111–1112 COPD, 1110 diabetes mellitus, 1112 macular degeneration, 1113 peripheral vascular disease, 1112 Health teams, 19t composition of, 21 teamlet model, 21 types of team models, 20–21 Healthy Aging: A Longitudinal Study in Europe, 105, 106t–107t Hearing aids, 318 Hearing loss, 315–318 acoustic neuroma, 316–317 otosclerosis, 316 possibly causing delirium, 1080b presbycusis, 316 screening for, in elderly patients, 35 sudden sensorineural, 302 treatment, 317–318 in young children, 426b Hearing screening, in healthy children, 426–427 Heart chambers of, 534f of newborn, 408 Heart disease complication of obesity, 809 prevention, 100–103 preventive services, 81–84 Heart healthy measures, 104f Heart rate, in neonate, 411 Heat illness, exertional, 586, 587t Height and weight, measurement, 826 Helicobacter pylori laboratory test, 192 risk factor for peptic ulcer disease, 849 HELLP syndrome, 379, 895 Hemagglutinins, 210 Hemangiomas infantile, 695 lateral neck, 339 of salivary glands, 341 Hematocrit (Hct), 187t Hematologic tests, 827 Hematoma auricular, 309 subungual, evacuation of, 566

Hematopoiesis, 877–878 Hematopoietic tumors, 898 Hematuria in adults, 904–906 in athletes, 594 in children and adolescents, 906–907 Heme-positive urine, 901 Hemochromatosis, 1014t Hemoglobin (Hb), 187t Hemolysis acquired forms of, 887 exertional, 593 extravascular, 885–886 intravascular, 885 Hemolytic anemia, 194t Hemolytic-hemorrhagic anemia, 885–886 Hemolytic uremic syndrome, 885, 894–895 Hemorrhage postpartum, 400–401 subarachnoid, smoking as risk factor, 1112 subconjunctival, 934 Hemorrhoids external, 567–568 internal, 566–567 Henoch-Schönlein purpura, 688 Heparin therapy for deep vein thrombosis in stroke, 969–970 and PTT, 185 for unstable angina, 504–505 Hepatitis, 856–861 serology, 192–193 Hepatitis A, 856–858 vaccine, 439 Hepatitis B, 858–859 screening, 219t vaccine, 439 Hepatitis B surface antigen (HBsAg), 192 Hepatitis C, 193, 859 Hepatitis D, 859 Hepatitis E, 859 Hepatotoxicity, with antilipidemics, 485b Herbal remedies, 1141 drug interactions with, 1142t–1147t types of formulations, 1143t Hereditary neuropathies, 993 Hereditary nonpolyposis colorectal cancer, 874b Herniation, disk, 634–635, 641–642 Heroin pharmacology, 1129 street names, 1125t Herpes genitalis, 920 Herpes gingivostomatitis, 713f Herpes gladiatorum, 591 Herpes simplex virus, 219–220 and HIV/AIDS, 251 involving eye, 948 primary ocular infection, 935 skin infections, 713–714 type 2 (HSV-2), 920 Herpesvirus, in pregnancy, 370 Herpes zoster oticus, 318 Herpes zoster (shingles), 213–214, 714 involving eye, 948 Herpetic infections, corneal, 935 Heterophile antibody, 195, 214 Hiccupping, in terminally ill patient, 67

1149

Index Hidden communication, 158 High-altitude cerebral edema, 588 High ankle sprains, 626–627 High-density lipoprotein (HDL), 194, 480–481 in metabolic syndrome, 493–495 reductions, in diabetes, 496 High-grade AV block, 540 Highly active antiretroviral therapy (HAART), 256 Hips, of newborn, 409–410 His-Purkinje tissue, 533 Historical perspective on CAM, 133t on crisis, trauma, and disaster theory, 1022–1023 of HIV/AIDS crisis and development of therapy, 249b on hospice care, 68 on medical home, 17 Histrionic personality disorder, 1041t–1047t, 1056 H1N1 virus, in pregnancy, 371 Hoarseness, 336 Holistic medicine, 132 Homeopathy, 142t, 143–144 Home safety, for neonate, 418–419 Homocysteine, 498 Hope, in dealing with terminal illness, 59 HOPE mnemonic, 141t Hormone replacement therapy (HRT), 466 clinical evidence from published research, 112–113 interpreting study results, 115 randomized controlled trials, 113–114 Women’s Health Initiative study, 114t Horny goat weed, 1142t–1147t Horse chestnut, 1161t, 1142t–1147t Hospice care, 68–69 for dementia patient, 1090 Hospital care for dementia patient, 1090 of diabetic patients, 748–749 Hospitalized patient: nutrition decisions caloric requirements, 837 enteral nutrition, 838 macronutrient requirements, 837 parenteral nutrition, 838 subjective global assessment, 836–837 when to start nutritional supplementation, 837–838 Human bites, 235–237 β-Human chorionic gonadotropin (HCG), 368t Human immunodeficiency virus (HIV) approach to patient, 254–255 classification and staging of HIV/AIDS, 251–252 dementia associated with, 1089 diagnosis, 253–254 epidemiology, 248–249 FUO associated with, 241b inflammatory neuropathies in, 992 laboratory test, 193 life cycle of HIV and relevance to treatment, 250–251 lymph node enlargement with, 340 modes of transmission and relative risk, 249–250

1150

Human immunodeficiency virus (Continued) natural history and clinical course, 252–253 pathophysiology, 250 in pregnancy, 370–371 preventive services, 87–88 retroviral agents, 255–259 screening, 219t TB in, 216t Human monocytic ehrlichiosis, 228, 229t Human papillomavirus (HPV), 224–225, 920 vaccine, 440 Human sexuality female sexual dysfunction, 1002–1005 initial evaluation of sexual problems, 1000–1002 issues in adolescence, 1009–1011 in later adulthood, 1011–1012 male sexual dysfunction, 1005–1008 models of sexual response, 1000 sexual orientation spectrum, 1008–1009 sexual self-concept, 1000 Humor, in establishing rapport, 159 Hydatidiform mole, 377 Hydrocele, 910 Hydrocephalus, normal-pressure, 1088–1089 Hydrocodone dosing data, 62t–64t pharmacology, 1129 street names, 1125t Hydrocodone plus homatropine, 61t Hydrocolloid wound dressings, 45t Hydrogel wound dressings, 45t Hydromorphone, dosing data, 62t–64t Hydronephrosis, fetal, 910 γ-Hydroxybutyrate (GHB), 1129, 1155t–1159t 5-Hydroxytryptophan (5-HT), 1155t–1159t 25-Hydroxyvitamin D, 204 Hydroxyzine, 1074–1075 Hygiene, sleep, 443b Hygiene hypothesis, 343 Hyoscyamine, in elderly, 46t Hyperbilirubinemia, in newborn, 416 Hypercalcemia, 183, 184t, 796–799, 798t–799t Hypercalciuria, 907 Hyperchloremia, 184–185 Hypercholesterolemia, risk factor for stroke, 966 Hypercortisolemia, 762–763 Hypercortisolism, 780–783 Hyperfunctioning pituitary adenomas, 761–762 Hyperglycemia, 192 with exercise, in diabetes mellitus, 738 in stroke, 970 Hypergonadotropic hypogonadism, 787 Hyperinsulinemia, 736 Hyperkalemia, 197, 198t Hyperlipidemia, 81–83 diet in prevention of, 833 genomic applications, 1014t risk factor for PVD, 520 Hypermagnesemia, 195, 196t Hypernatremia, 200t, 201 Hyperparathyroidism, primary, 796, 798t Hyperphosphatemia, 196, 799, 800b Hyperprolactinemia, 761–762 Hypersensitivity pneumonitis, 293–294

Hypertension, 81 accompanying diabetes, 496, 736, 752 in children, 422 chronic, in pregnancy, 373–374 complication of obesity, 808 diet in prevention of, 831–833 gestational, 380 pulmonary, 289–290 recommendations, 486–492 risk factor for PVD, 520 stroke, 966 Hypertensive retinopathy, 953 Hyperthyroidism, 203 Graves disease, 769–770 thyroxine-producing nodules, 770 Hypertonia, of neonate, 412 Hypertrophic scars, 558 Hypertrophy adenoid, 321 turbinate, 322 Hyperuricemia, 201t, 203, 668–670 Hyperuricosuria, 203 Hypervolemic hyponatremia, 200–201 Hyphema, traumatic, 938–939 Hypoactive sexual desire disorder, 1002–1003 Hypoalbuminemia, effect on ESR, 190t Hypocalcemia, 183, 184t, 799 Hypochloremia, 184–185 Hypochondriasis, 1040b, 1041t–1047t, 1058 Hypochromic RBCs, 883f Hypoglossal nerve (CN XII), 960–961 Hypoglycemia, 191 with exercise, in diabetes mellitus, 738 in term newborn, 415 Hypogonadism male, 789 secondary, 760–761 Hypogonadotropic hypogonadism, 759, 787, 789b Hypokalemia, 197, 782 Hypomagnesemia, 183, 195, 196t Hyponatremia, 200t exertional, 586–587 Hypophosphatemia, 196–197, 800 Hypopituitarism, 757–761 clinical manifestations, 758–759 diagnosis, 759–760 Hypoproliferative anemia, 882–883 Hypospadias, 910 Hypothalamic-pituitary axis, 756–757 Hypothermia, in sports, 588 Hypothyroidism, 203 central, 772 chronic autoimmune thyroiditis, 771–772 and obesity, 808 Hypotonia, of neonate, 412 Hypouricemia, 203 Hypovolemic hyponatremia, 200 Hypoxia, in stroke, 969–970 Hytrin. See Terazosin

I Idiopathic acute peripheral facial paralysis, 994 Idiopathic hypopituitarism, 757–758 Idiopathic myelofibrosis, 888 Idiopathic osteoarthritis, 656t

Index Idiopathic pulmonary fibrosis, 296f Idiopathic rhinitis, 323 Idiopathic thrombocytopenic purpura, 893–894 Illness. See also Disease altitude, 588 chronic, 9 and psychosocial intervention, 30 heat, 586 medical, interaction with anxiety and depression, 1062–1063 in neonate, preventing and recognizing, 419 rank order of chronic conditions, 15t Imaging studies for dementia, 1084 for osteoarthritis, 656 of rheumatic diseases, 653 for thyroid disorders, 768–769 of urinary tract, 903 Immune destruction, accelerated platelet removal caused by, 893–894 Immunizations for children and adolescents, 91, 437–441 in pregnancy, 369t, 371 for skin injury, 552 Immunochemical FOBT, 190–191 Immunoglobulin A (IgA) antiendomysial antibodies, 873 Immunoglobulin G, 192 Immunotherapy for allergic rhinitis, 346 for asthma, 271 Impetiginized atopic dermatitis, 694f Impetigo, 233t, 706 Impingement syndrome, shoulder, 604–608 Implants, contraceptive, 475 Impulse conduction, changes in, 535 Imuran. See Azathioprine Inborn errors of metabolism, 651 Incidence of concussion in sports, 582–583 of diabetes mellitus, 495 statistical expression, 76 Incision of cutaneous abscess, 564–565 of paronychia, 566f Inclusion cysts, epidermal, 724 Incomplete isosexual precocity, 788t Incontinence, urinary, 915–916 in elderly, 47–52 Incretin agonist, 741 Indinavir sulfate, 258t Individualization, of patient education, 161 Individualized education plan (IEP), 436 Indomethacin, in elderly, 46t Induction of labor, 386–387 Infantile hemangioma, 695 Infantile regurgitation, 844–847 Infants. See also Neonates causes of pneumonia, 280 in clinical interview, 172 of diabetic mother, 415–416 differential diagnosis for FUO, 241b hunger and fullness cues, 829f international mortality rate, 360b nutrition, 428–430 red eye in, 930–932 Infection control, for pressure ulcers, 44

Infectious arthritis Lyme disease, 676 Pott’s disease, 677 septic arthritis, 675–676 Infectious diseases acute bronchitis, 279 AIDS-related pulmonary infections, 284–287 bite infections, 235 bone and joint infections, 237–239 bronchiolitis in children, 278–279 bronchitis, 208–209 cellulitis, 231–234 CNS infections, 243 complicated intra-abdominal infections, 242 diabetic ulcers, 234–235 fever of unknown origin, 240–242 furuncles and carbuncles, 232–234 genitourinary infections, 225–227 infectious diarrhea, 244–246 influenza, 210–212 mononucleosis, 195–196, 214, 590–591 in neonate, 413 pneumonia, 209–212, 279–282 in pregnancy, 369–371 preventive services, 86–88 spontaneous bacterial peritonitis, 242–243 STIs, 218–222 systemic viral infections, 212–214 teratogenic, 403b tick-borne infections, 228 tuberculosis, 215–218, 282–284 urinary tract, 918–923 Infectious etiologies, of type 1 diabetes, 734 Infectious skin diseases bacterial infections, 705–707 abscesses, 707 cellulitis, 706–707 erysipelas (St. Anthony’s fire), 706 erythrasma, 707 folliculitis, 707 impetigo, 706 fungal infections dermatophytosis, 708 onychomycosis, 711 tinea capitis, 710–711 tinea corporis, 708 tinea cruris, 710 tinea pedis, 708–710 tinea versicolor, 711–713 viral infections herpes simplex, 713–714 herpes zoster (shingles), 714 molluscum contagiosum, 715–716 verruca (warts), 714–715 Infertility female, 793–794 male, 790 Infestations pediculosis capitis, 717–718 pediculosis corporis, 718 Pthirus pubis (pubic lice), 718 scabies, 716–717 Inflammatory bowel disease (IBD), 863–866 Inflammatory dermatologic diseases contact dermatitis, 702–703 dyshidrotic eczema, 703–704

Inflammatory dermatologic diseases (Continued) erythema nodosum, 705 generalized exfoliative dermatitis, 704–705 granuloma annulare, 705 lichen planus, 701–702 lichen simplex chronicus, 702 nummular dermatitis, 704 pityriasis rosea, 700–701 psoriasis, 698–700 rosacea, 701 seborrhea, 698 stasis dermatitis, 704 Inflammatory disorders myopathies, 683–684 neck masses, 340–341 neuropathies, 992 rheumatic fever, 677–678 of salivary glands, 341 Inflammatory phase of healing, 556 Influenza, 210–212 in pregnancy, 371 Influenza A virus, 212f Information distorted, 146 medical POEMs, 126 usefulness of, 125 sources, 116, 117t Informational control, 28 Information technology and components of patient care, 120–122 office business and management functions, 122 systems integration and connection, 122–123 Infusion, herbal, 1143t Ingrown nail, 565 Inhaled corticosteroids, for asthma, 271, 273t Inhalers, nicotine, 1119b, 1120 Inheritance patterns, 1015t, 1019t Inhibin A, 368t Injections opioids or antiemetics, 67 periurethral, 52 therapeutic corticosteroid, 654 Injury grades, for acromioclavicular joint, 604 Inositol hexaphosphate (IP-6), 1155t–1159t Instability, shoulder, 608–610 Institute of Medicine 2005 Report, on CAM, 136–137, 138t Instrumental support, 26 Insulin pump therapy, 744 Insulin rebound, 744 Insulin resistance genetic disorders of, 734 in metabolic syndrome, 493–494 Insulins basal bolus insulin, 743 children and adolescents requiring, 743–744 initiating insulin for type 2 diabetes, 742–743 insulin pump therapy, 744 insulin rebound, 744 supplemental, 741 in treatment of diabetic ketoacidosis, 746 Integrase strand transfer inhibitors (INSTIs), 256–257

1151

Index Integrative medicine, 132 core elements of, 139 Intelence. See Etravirine Interdigital neuropathy, 992 Interdisciplinary health team, 20–21, 22t Interferon-γ release assays, 218 Intermediate-acting human insulin, 742t Intermittent asthma, 350 Intermittent claudication, 519 Internal hemorrhoids, 566–567 International Classification of Diseases (ICD-9) codes, for contraception reimbursement, 469t Internet, rheumatology information, 688 Interpersonal skills, of family physician, 12 Interpretation, 1050 Interrupted sutures, 560 Interruption during interview process, 170 by physician, 159 Interstitial cystitis, 917 Interstitial lung diseases, 296–297 Interventions acute, for stroke, 967–968 in alcohol disease, 1098–1099 behavioral, for incontinence in elderly patients, 50 behavioral counseling, 5A components of, 93t for conduct disorder, 451 for difficult patients, 1044t–1047t FRAMES technique, 1126b lifestyle, focus on heart disease prevention, 100–103 in model of health behavior change, 162 for personality disorders, 1054–1059 strategies, for falls in elderly patients, 39 using psychosocial data, 29–30 Interventions for obesity in adults, 811–812 CAM, 815 in children, 810–811 medications, 814–815 setting goals, 812 surgery, 815–817 Intervertebral disk, 643f Interviewing barriers to effective communication, 169–170 basic communication, 168 content and process, 166 cultural competency, 171–172 with difficult patient, 1049 difficult patient situations, 169 initial evaluation of sexual problems, 1000–1002 listening environment, 167–168 maximizing time, 168 motivational, 108–109, 162 patient participation, 169 questions regarding alcohol use, 1093–1094 religion and spiritual issues, 170–171 of specific groups, 172–174 Intimate partner violence, 1023–1025, 1032–1035 couples, 1033–1034 documentation and reporting, 1034–1035 general recommendations, 1033

1152

Intimate partner violence (Continued) safety planning, 1034 screening, 1033 treatment of intimate batterers, 1033 Intimate space, 157 Intoxication alcohol, 1094–1099 opiates, 1129 sedative-hypnotics, 1130 Intra-abdominal infections, complicated, 242 Intracranial complications of otitis media, 314–315 of sinusitis, 325t Intradermal contraceptive device, 571 Intrapartum procedures diagnostic ultrasound, 396–397 episiotomy, 396 forceps delivery, 398 obstetric anesthesia, 395–396 operative vaginal deliveries, 397 vacuum extraction, 398–399 Intrasellar pituitary tumors, 758 Intratemporal complications, of otitis media, 314 Intrathoracic pressure, increased, in SIADH, 765b Intrauterine contraceptives, 475–476, 570–571 Intrauterine growth restriction, 378–379 Intravascular hemolysis, 885 Intravenous urography, 903 Intrinsic risk factors, for pressure ulcers, 43 Inverse psoriasis, 698, 699f, 711f Inversion ankle injury, 624 Inverted subcutaneous stitches, 560f Invirase. See Saquinavir mesylate Involuntary (passive) smoking, 1114–1115 Iodine, nutritional summary, 820t–824t Iritis, 935 Iron nutritional summary, 820t–824t supplements, 1147t–1154t Iron deficiency anemia, 193, 372, 884 prevalence, 880t screening in children, 427 in sports, 593 Iron studies, 193 Irritable bowel syndrome (IBS), 866–868 Irritant contact dermatitis, 702–703 Irritants, pulmonary, 294 Irritant vaginitis, 463 Ischemia, critical limb, 519–520 Isentress. See Raltegravir Isolated virilization, 788t Ixodes tick, 228, 229t

J Jaundice, in newborn, 416 Jejunoileal bypass, 815 Jitteriness, of neonate, 413 Joint disease deformities of rheumatoid arthritis, 660 pseudogout, 671 septic arthritis, 240 symptom evaluation, 648–650 Juice, herbal, 1143t Junctional rhythms, 538–539 Juvenile rheumatoid arthritis, 687

K Kaletra. See Lopinavir and ritonavir Kallmann syndrome, 758, 789 Kaposi’s sarcoma, 285 Kava, 1142t–1147t Kawasaki’s syndrome, 688 Kegel exercises, 50 Keloids, 556 Keratitis, herpes zoster, 949f Keratitis sicca, 949–950 Keratoconjunctivitis sicca, 682 Keratosis actinic, 724–725 seborrheic, 723 Keratosis pilaris, 694 Ketamine pharmacology, 1128–1129 street names, 1125t Ketoacidosis, diabetic, 744–747 Ketones, in urine, 901 Kidney disease chronic, 912–913 smoking-related cancer, 1110 Kiesselbach’s plexus, 303, 304f Klinefelter’s syndrome, 789 Knee degenerative osteoarthritis, 616–618 infections, 618 ligamentous injuries, 621–624 meniscus injuries, 619–621 patellofemoral syndrome, 618–619 Knee–chest pulls, 641f

L Labial adhesions, 910 Labor and delivery abnormalities of, 387–389 complications of early labor ectopic pregnancy, 375–376 molar pregnancy, 377 spontaneous abortion, 376–377 intrapartum procedures diagnostic ultrasound, 396–397 episiotomy, 396 forceps delivery, 398 obstetric anesthesia, 395–396 operative vaginal deliveries, 397 vacuum extraction, 398–399 normal induction of labor, 386–387 progress of labor, 384–386 preterm, 377–378 vaginal birth after cesarean, 393–395 Laboratory findings in Cushing’s syndrome, 780–781 in diabetic ketoacidosis, 745–746 in pheochromocytoma, 783–784 in primary adrenal insufficiency, 779 Laboratory tests albumin, 180 alkaline phosphatase (ALP), 180 aminotransferases, 180–181 amylase and lipase, 181 for anemia, 881–882 anti-cyclic citrullinated peptide antibodies, 199

Index Laboratory tests (Continued) antinuclear antibodies (ANAs), 181–182 assessment of protein status, 826–827 bicarbonate, 188–189 bilirubin, 182–183 blood urea nitrogen (BUN), 183 calcium, 183 carbon dioxide, 188–189 carcinoembryonic antigen (CEA), 183–184 chloride, 184–185 coagulation studies, 185 complete blood count (CBC), 186–188 concept of normal, 176–177 to confirm diagnosis of anaphylaxis, 355t considerations for ordering tests, 179–180 C-reactive protein (CRP), 189 creatinine, 183 for dementia, 1084 erythrocyte sedimentation rate (ESR), 189–190 evaluating test’s performance characteristics, 177 fecal occult blood test (FOBT), 190–191 at first prenatal visit, 364b folic acid deficiency, 186 glucose, 191–192 glycosylated hemoglobin (Hb A1C), 192 Helicobacter pylori, 192 hematologic, 827 hepatitis serology, 192–193 HIV, 193, 257t iron studies, 193 lipid profile, 194 magnesium, 195 in monitoring rheumatic disease, 652–655 mononucleosis (EBV infection), 195–196 multiple test ordering, 179 natriuretic peptides (BNP and N-terminal pro-BNP), 196 for osteoarthritis, 656 for peripheral neuropathies, 988–989 phosphorus, 196–197 potassium, 197 pregnancy tests, 197 prostate-specific antigen (PSA), 197–198 for rheumatoid arthritis, 661 rheumatoid factor, 199 separating diseased from disease-free persons, 177–204 sodium, 199–201 streptococcal testing, 201–202 in substance use disorder screening, 1127 syphilis testing, 202 thyroid testing, 202–203, 768t total protein, 198–199 uric acid, 203 urinalysis, 900–902 urinary creatinine, 827 urine culture, 902 urine drug screens, 203–204 for viral hepatitis, 859t vitamin and mineral assays, 827 vitamin B12 deficiency, 186 vitamin D, 204 Labyrinthitis, 308, 985–986

Lacerations corneal and scleral, 938 of external ear, 311 perineal and vaginal, 396b Lachman test, 623f Lactation, 399–400 nutrition and, 827–828 Lactational amenorrhea method, 473 Lamivudine, 258t Language body language, 150–157 developmental milestones in young children, 434t–435t positive, 57t Laryngitis, 334 reflux, 338 Laryngomalacia, 335 Larynx cancer, 338 smoking-related, 1109 hoarseness, 336 initial evaluation, 333–334 laryngitis, 334 radiography, 334 reflux laryngitis, 338 special studies, 334 stridor, 334–336 trauma to, 336 vocal cord nodules, 337–338 vocal cord paralysis, 336–337 Latent autoimmune diabetes of adults (LADA), 733–734 Latent lupus, 679 Latent phase of first stage of labor, 384 prolonged, 388 Latent syphilis, 221t Latent TB infection (LTBI), and purified protein derivative, 216–218 Late pregnancy complications abruptio placentae, 380 eclampsia, 379–380 gestational hypertension, 380 HELLP syndrome, 379 intrauterine growth restriction, 378–379 placental abnormalities, 381–382 placenta previa, 380–381 preeclampsia, 379 preterm labor, 377–378 vasa previa, 381 Lateral ankle sprains, 624–626 Lateral collateral ligament injuries, 621 Lateral elbow tendinopathy, 610–611 Lateral neck masses, 339 Laying on of hands, 150 Leading causes of death in U.S. (2006), 77t, 101t Lead toxicity screening, in children, 427 LEARN acronym, 29 Learning disabilities, and the eye, 945 Lea’s Shield, 569–570 Leflunomide, for rheumatoid arthritis, 665 Left ventricular systolic dysfunction, pharmacologic therapy, 510 Legal issues, in genetic testing, 1018 Legal options, for child with conduct disorder, 451 Legs, in body language, 155 Leg swelling, 524t

Lens opacities complete, 946 partial, 945–946 Leopold’s maneuvers, 366f Leprosy, 992 Lesbian patients, 1008 Lethargy, of neonate, 412 Leukemia, smoking-related, 1110 Leukocyte esterase, 901 Leukocytosis, 188, 189t, 889 Leukopenia, 189t Levitra. See Vardenafil Levodopa, 995 Levonorgestrel intrauterine system, 476 Levothyroxine, 760 Lewy bodies, dementia with, 971, 995 Lewy body disease, 1087–1088 Lexiva. See Fosamprenavir calcium Lichen planus, 701–702 Lichen sclerosus, 464 Lichen simplex chronicus, 702 Licorice, 1142t–1147t Life expectancy, increase in, 33 Life span perspective, 28 Lifestyle and diet, behavioral modification to improve, 838–840 healthy, what it is, 110 interventions, focus on heart disease prevention, 100–103 and obesity, 806–807 primary prevention, 103–108 physician’s belief in, 109–110 Lifestyle change in GERD management, 853b and motivational interviewing, 108–109 obstacles to, 110 therapeutic, 481t–482t Lift-off test, 606–607, 608f Ligamentous injuries, of knee, 621–624 Limb ischemia acute, 524t chronic, 525t critical, 519–520, 522 Lindemann, Eric, 1022–1023 Linezolid, 233t Lipase, laboratory test, 181 Lipid profile, 194 Lipomas, 565 of neck, 339 Lipoprotein(a), as predictor of PVD, 521 Lisdexamfetamine, 449t Listening to dying patient, 55 good listening, 158–159 in interviewing, 167–168 motivational interviewing, 108–109 Literacy, health, 164 Live cycle, of HIV, 250–251 Liver chemistry tests, 180–181 Liver disease ALP increase due to, 181t and CEA level, 184t cirrhosis, 859–861 hepatitis, 856–859 smoking-related cancer, 1110 Living will, 70 Local anesthesia, 554

1153

Index Lone star tick, 229t, 230f Long-acting synthetic insulins, 742t Long QT syndrome, 543–544 Long-term follow-up, of thyroid disorders, 774 Loop diuretics, 184t Loop monitors, implantable, 535 Lopinavir and ritonavir, 258t Lortab. See Hydrocodone Loss of vision, sudden, 952t Low back pain, 638–641 assessment, 640 treatment, 640–641 Low-density lipoprotein (LDL), 194, 480 in metabolic syndrome, 493–495 reductions, in diabetes, 496 target levels, 481–482 Lower extremity examination, for rheumatoid arthritis, 660 Lower GI tract disease celiac disease, 872–873 colorectal cancer, 873–876 diverticular disease, 870–872 IBD, 863–866 IBS, 866–868 lower GI bleeding, 868–870 Lower urinary tract symptoms, 907 Low ferritin, in nonanemic athlete, 593 Lozenges, nicotine, 1119b, 1120 LSD detection time, 1127t intoxication and withdrawal symptoms, 1130t street names, 1125t Lumbar disk syndromes, 641–644 Lumbar spine, radiographs, 639f Lumbosacral neuropathy, 991 Lung cancer, 80 and CEA level, 184t prevention, 292 smoking-related, 1107–1109 treatment, 291–292 Lung disease acute infectious diseases, 278–282 bronchoscopy, 266 chest radiography, 264–266 chronic infectious diseases, 282–287 common pulmonary symptoms, 266–268 diagnostic tools in pulmonary medicine, 262–263 fungal infections, 287 granulomatous diseases, 294–295 interstitial, 296–297 lung manifestations of autoimmune connective tissue disorders, 297 malignant disease, 291–292 measurement of blood gases, 266 obstructive, 268–278 acute respiratory failure, 277 asthma, 269–273 COPD, 273–277 occupational, 292–294 of pleura and extrapulmonary space, 297–298 pulmonary complications of sickle cell disease, 290–291 pulmonary function testing, 263–264 risk factors, 261–262 vascular disease, 287–290

1154

Lung(s) age-related decline in function, 1118f breathing disorders, 298–299 of newborn, 408 Lupus erythematosus (LE), skin signs of, 720–722 Lupus nephritis, 679, 681 Lutein, 1155t–1159t Lycopene, 1155t–1159t Lying, detection of, 157 Lyme disease, 230 and inflammatory neuropathy, 992 treatment, 676–677 Lymphadenitis, cervical, 340 Lymphadenopathy, 896–898 Lymphangiomas, 339 Lymphocyte disorders, 896–898 Lymphocytic hypophysitis, 758 Lymphocytopenia, 896 Lymphocytosis, 896 Lymphoepithelial cysts, 341 Lymphogranuloma venereum (LGV), 222 Lymphoid tissue tumors, 898 Lymphomas causing FUO, 241b neck, 340 Lyrica. See Pregabalin

M Macroangiopathy, diabetic, 752 Macrocytosis, 884 effect on ESR, 190t Macronutrient requirements, for hospitalized patient, 837 Macroprolactinemia, 762 Macular degeneration, 952–953 smoking as risk factor, 1113 Maculopapular reaction, 719 Maculopathy, age-related, 952f Magnesium laboratory test, 195 nutritional summary, 820t–824t supplements, 1147t–1154t Magnesium sulfate therapy, for preterm labor, 378, 379b Magnetic resonance angiography (MRA), for PVD, 527–529 Magnetic resonance imaging (MRI), evaluation of urinary tract, 903 Maintenance of certification, 5 Major alcohol withdrawal, 1096–1097 Major depressive disorder, 1028t–1029t management and treatment, 1069–1077 Major depressive episode, diagnostic criteria, 1063b Malabsorptive procedures, 815 Male condom, 470–471 Male hypogonadism, 789 Male infertility, 790 Male menopause, 1011–1012 Male sexual dysfunction dyspareunia, 1008 erectile dysfunction, 1005–1007 orgasmic disorder, 1008 premature (rapid) ejaculation, 1007–1008 Malingering, 1040b, 1041t–1047t, 1055

Management algorithm, for somatization, 1053–1054 Manganese nutritional summary, 820t–824t supplements, 1147t–1154t Maraviroc, 258t Marijuana intoxication and withdrawal symptoms, 1130t pharmacology, 1128 street names, 1125t Masked communication, 158 Masses breast, 573 neck, 339 pelvic, differential diagnosis, 460t scrotal, 910t thyroid, 341–342, 773–774 Masturbation, 1009 Maternal biochemical screening, 367–368 Maturation disorders iron deficiency, 884 neutropenia, 890b RBC production in, 883 thalassemia, 884–885 Maturity neuromuscular and physical, 410b, 411f sexual, in boys and girls, 425t Maturity-onset diabetes of young, 734 McRoberts maneuver, 389 Mean corpuscular hemoglobin (MCH), 187t Meaning of stressor, 1026 Measles, 214, 697 vaccine, 438 Mechanical debridement, for pressure ulcers, 44 Meconium, 385 delayed passage of, 413 Meconium aspiration syndrome, 406 Medial ankle sprains, 626 Medial collateral ligament injuries, 621 Medial elbow tendinopathy, 611 Medial tibial stress syndrome, 596 Median neuropathy, 990 Medical assessment, of elderly patients, 34–35 Medical home assisting patients with dietary change, 840 checklist for, 22 goals of, 17–20 health teams, 20–22 history, 17 patient-centered, 15, 18t and psychosocial issues, 31 ways to access, 21f Medical information POEMs, 126 usefulness of, 125 Medical literature, building clinical evidence from published research, 112–113 Medical nutrition therapy, 834 Medicare, and Alzheimer’s disease, 1087b Medication-overuse headaches, 965 Medications. See also Drugs affecting male sexual function, 1005b associated with dizziness, 985b migraine, 963t and obesity, 807 for obesity management, 814–815

Index Medications (Continued) ocular, 948 prescribing for difficult patients, 1051–1052 preventive, for children, 91 selection for depression, 1069–1072 for symptoms of psychiatric disorders, 1035–1036 for therapy of anaphylaxis, 356b used by elderly patients rational drug prescribing, 45–47 review of, 35 Megakaryocytes, 892 Megaloblastic anemia, 194t Meglitinides, 739–740 Melanocytic nevi, 694–695 Melanoma, 562, 728–730 choroidal, 951–952 Melatonin, 1161t drug interactions, 1155t–1159t Ménière’s disease, 307, 985–986 Meningitis, 325t bacterial, 243–244, 975–981 Cryptococcus neoformans, 259t recurrent, 981 viral, 983 Meningococcal conjugate vaccine, 440 Meniscus injuries, 619–621 Menopause, 466 male, 1011–1012 symptoms of, 792t Menorrhagia, 457b Menstrual cycle, in female athlete, 599 Mental health preventive services, 84–86 smoking and, 1116 and substance abuse, 1133 Mental status examination, 959 Meperidine, 61 dosing data, 62t–64t in elderly, 46t Meprobamate, in elderly, 46t Meralgia paresthetica, 991 Meta-analysis, in HRT, 113 Metabolic acidosis, 188 Metabolic alkalosis, 188 Metabolic conditions, preventive services, 88–90 Metabolic disorders, possibly causing delirium, 1080b Metabolic factors, for obesity, 807–808 Metabolic neuropathies, 992–993 Metabolic syndrome cardiovascular risk factors, 492–494 diabetes and, 753–754 dietary recommendations and, 835 and obesity, 809 treatment, 494–495 Metabolism and excretion, conditions affecting, 825t Metadate. See Methylphenidate Metallic foreign bodies, in eye, 938 Metatarsal fractures, 629 Metformin, 739, 747 Methadone, 61 detection time, 1127t dosing data, 62t–64t in medical management, 1131 pharmacology, 1129

Methamphetamine, 449t pharmacology, 1128 street names, 1125t Methicillin-resistant Staphylococcus aureus (MRSA), 233t Methicillin-susceptible Staphylococcus aureus (MSSA), 233t Methotrexate, for rheumatoid arthritis, 663–665 N-Methyl-D-aspartate (NMDA) antagonist, 996t Methyldopa, in elderly, 46t Methylenedioxymethamphetamine (MDMA) intoxication and withdrawal symptoms, 1130t street names, 1125t Methylergonovine, 400 Methylphenidate for ADHD, 448, 449t street names, 1125t 15-Methylprostaglandin F2α, 400 Methylsulfonylmethane (MSM), 1155t–1159t Microalbuminuria, 751 Micro-expressions, in body language, 153 Micronutrients, in diabetes, 835 Middle ear disorders barotrauma and barotitis, 315 bullous myringitis, 311 otitis media, 311–315 traumatic tympanic membrane perforations, 315 Midline neck masses, 339 Mifflin-St. Jeor equation, 837 Migraine, 962–964 Mild neutropenia, 891 Mild persistent asthma, 351–352 Milk, and infant formulas, 429t Milk thistle, 1161t, 1142t–1147t Mind–body medicine, 139–140 Mineral assays, 827 M2 inhibitors, 213t Mini-mental status examination, 972t Mini Nutritional Assessment (MNA), 832f Minocycline, 233t Minorities and HIV/AIDS, 249 substance use disorders and, 1133 Mirena IUD, 570 Mirroring, in body language, 151–152 Mirtazapine, 1071t Miscarriage, uterine aspiration for, 573 Misconceptions, about biopsychosocial model, 26–27 Misoprostol, 386b, 658 Mitoxantrone, 999 Mitral regurgitation, 516–517 Mitral stenosis, 515–516 Mitral valve prolapse, 517–518 Mixed hearing loss, 316 Mixed incontinence, 49 Models of human sexual response, 1000 Moderate persistent asthma, 352 Modes of transmission, of HIV, 249–250 Mogen clamp, 575 Molar pregnancy, 377 Moles, atypical, excision of, 562–563 Molluscum contagiosum, 715–716 Molybdenum, nutritional summary, 820t–824t

Monoamine oxidase inhibitors effect on therapy in anaphylaxis, 357t type B, 996t Monoarticular symptoms, 649f Monocyte and macrophage disorders, 892 Mononeuropathies, 750, 989–992 Mononucleosis infectious, 214 laboratory test, 195–196 in sports medicine, 590–591 Mood disorders, diagnosis, 1063–1066 Mood stabilizers, doses, 1052t Morbidity, of intimate partner violence, 1024–1025 Morbilliform eruption, 719 Moro reflex, 407 Morphine dosing data, 62t–64t oral, for pain control, 60 Mortality rate, infant, 397f Motivational enhancement therapy, for substance use disorders, 1132 Motivational interviewing, 108–109, 162, 839 Motor changes, in peripheral neuropathies, 987 Motor examination, 961 Mucocele, 325t Mucocutaneous manifestations of SLE, 679 Multidisciplinary health team, 20–21, 22t Multi-Factored Evaluation (MFE), 436 Multifactorial diseases, 1019t Multiple gestation, 382 Multiple sclerosis clinical course, 998 diagnosis, 997–998 treatment, 998–999 Multiple test ordering, 179 Multisystem atrophy, 995 Mumps, 341 vaccine, 438 Mupirocin ointment, 233t Muscle injuries in sports histopathology, 595 mechanism of injury, 594–595 muscle strains, 595 Muscle relaxants, in elderly, 46t Muscles, of newborn, 409–410 Muscle tone, 961 Musculoskeletal causes of chronic pelvic pain, 465b Musculoskeletal manifestations of SLE, 679 Musculoskeletal office procedures aspiration of knee joint, 575–576 shoulder injection, 576 Musculoskeletal symptoms, evaluation of, 648–650 Myasthenia gravis, ocular findings, 949 Mycobacterium avium complex, 259t Mycobacterium tuberculosis, 251 Myeloid growth factors, 891 Myeloproliferative disorders, 888 Myocardial infarction (MI) non-ST segment, 503–505 ST-segment elevation, 505–508 Myocardial perfusion imaging, 500–501 Myocytes, atrial and ventricular, 533 Myopathies, inflammatory, 683–684 MyPyramid food guidance system, 818

1155

Index

N Nafcillin, 233t Nail plate avulsion, for onychomycosis, 565 Nail psoriasis, 698 Nail surgery, 565–566 Naloxone, 1129 Naltrexone, 1100–1101, 1131 Napoleon test, 606–607, 608f Narcissistic personality disorder, 1041t–1047t, 1057 Narcolepsy, 445 Narcotics, for pain control, 61t Nasal obstruction, 320–321 Nasal packing, 304 Nasal polyps, 321–322, 329, 346 perennial allergic rhinitis associated with, 346 Nasal spray, nicotine, 1119b, 1120 Nasal trauma, 329–330 Nasal vestibulitis, 321 Nasogastric feeding, 838 Nasolacrimal duct obstruction, 932 Natalizumab, 999 National Center for Complementary and Alternative Medicine (NCCAM), 132f Strategic Plan 2010, 137–139 National Childhood Vaccine Injury Act, 441 Natriuretic peptides, laboratory test, 196 Natural history of atherosclerosis, 521 of delirium, 1082 of HIV, 252–253 Naturopathy, 142t Nausea and vomiting with alcohol withdrawal, 1096t–1097t in terminally ill patient, 67 Neck congenital masses, 339 inflammatory masses, 340–341 neoplastic masses, 339–340 of newborn, 408 salivary gland disorders, 341 thyroid masses, 341–342 Needles, for sutures, 553 Neer test, 608f Negative emotions, chronic, 26 Negative predictive value, of laboratory test, 177 Neglect, of elderly, 41t Neisseria gonorrhoeae, 223 Nelfinavir mesylate, 258t Neonatal care audiology screening, 410 common problems encountered in term newborn, 415–417 initial evaluation, 406–410 postnatal assessment of gestational age, 410 preconception counseling, 402–403 preventing and recognizing illness, 419 signs and symptoms of concern differential diagnosis, 413–415 general observation, 410–411 respiratory symptoms, 412 signs that should raise concern, 412–413 vital signs, 411–412

1156

Neonatal resuscitation, 404–406 Neonates. See also Infants circumcision, 419, 574–575 developmental milestones, 434t–435t feeding and elimination habits, 418 safety at home, 418–419 transition from fetus to newborn, 403–406 Neoral. See Cyclosporine Neovascularization, 557f Nephritis, lupus, 679, 681 Nephropathy, diabetic, 751 Nerve damage, co-analgesics for, 66t Nerve glide exercises, carpal tunnel, 613f Nerve root innervations, 962t Neuralgia postherpetic, 214 trigeminal, 965 Neuraminidase, 210 Neuraminidase inhibitors, for influenza, 213t Neurapraxia, cervical cord, 585 Neuritis, optic, 957 Neurobiology, of anxiety and depression, 1061–1062 Neurochemical hypothesis of delirium, 1079 Neurodevelopment, behavior and, 431 Neuroendocrine factors, for obesity, 808 Neurofibrillary tangles, 1085 Neurolinguistic programming, 157 Neurologic conditions CNS infection and inflammation, 975–984 delirium, 970–971 dementia, 971–973 dizziness, 984–985 headaches, 962–965 multiple sclerosis, 997–999 Parkinson’s disease, 994–997 peripheral neuropathies, 986–994 seizures, 973–975 stroke (cerebrovascular accident), 965–970 Neurologic examination cranial nerve examination, 960–961 mental status examination, 959 motor examination, 961 of neonate, 407–408 reflexes, 961 sensory examination, 961 Neuromuscular maturity, 410b, 411f Neuronitis, vestibular, 307 Neuropathic pain, co-analgesics for, 65 Neuropathy diabetic, 750 pudendal, 594 Neuropsychiatric lupus, 679 Neurosyphilis, 202, 221t Neutropenia, 889–891 Neutrophil function disorder, 891 Neutrophilia, 889 Neutrophils, 188 disorders of, 889–891 Nevirapine, 258t Nevus dysplastic, 562 melanocytic, 694–695 Newborns. See Neonates Niacin (vitamin B3) for dyslipidemia, 485–486 nutritional summary, 820t–824t supplements, 1147t–1154t

Nicotine addiction cigars, 1113 cravings, 1105–1106 genetics, 1121 health risks, 1106–1116 involuntary (passive) smoking, 1114–1115 smoking cessation, 1116–1121 withdrawal guidelines, 1119b Nightmares, 444t Night terrors, 444t Night waking, 444 Nitrate therapy, for stable angina, 501–502 Nitric oxide, inhaled, for pulmonary hypertension, 290 Nitrite, in urine, 901 Nitrogen balance, 826–827 Nitrosamines, tobacco-specific, 1115 Nits, of head lice, 718f Nocturia, 907–908 Nocturnal enuresis, 914 Nodular basal cell carcinoma, 726–727 Nodules thyroid, 773–774 thyroxine-producing, 770 vocal cord, 337–338 Noise, chronic and acute exposure to, 317 Nonabsorbable sutures, 553 Nonaccidental inflicted neurotrauma, 939 Nonallergic rhinitis, 346 Nonarticular rheumatism, 688 Nonbacterial prostatitis, chronic, 913–914 Nondihydropyridines, 487t–489t Nongonococcal urethritis, 223, 920 Nonhealing wounds, 558 Noninvasive vascular study, for PVD, 525–527 Nonnucleoside reverse-transcriptase inhibitors (NNRTIs), 256–257, 258t Nonosmotic stimuli, in SIADH, 765b Nonproliferative diabetic retinopathy, 954f Nonsteroidal anti-inflammatory drugs. See NSAIDs Nonstress test, in antepartum fetal surveillance, 382–383 Non-ST-segment MI, 503–505 Nontoxic multinodular goiter, 341–342 Nonulcer dyspepsia, 848 Nonverbal communication, 149 Normal-pressure hydrocephalus, 1088–1089 Normal saline, in treatment of diabetic ketoacidosis, 746 Nose adenoid hypertrophy, 321 choanal atresia, 321 deviated septum, 322 epistaxis, 303–305, 320 foreign bodies, 321 hypertrophied turbinates, 322 obstruction, 320–321 patient history, 319 polyps, 321–322, 329 radiography, 319–320 rhinitis, 322–324 sinonasal tumors, 329 sinusitis, 324–329 trauma, 329–330 vestibulitis, 321 Nose rub, 156–157

Index NSAIDs dosing data, 66t effect on FOBT, 191 exposure in pregnancy, 369t for pain control, 60 for rheumatic diseases, 654 for rheumatoid arthritis, 666, 667t and risk for peptic ulcer disease, 850 Nuclear cataracts, 945 Nuclear sclerosis cataract, 950 Nuclear stress testing, 500–501 Nucleic acid amplification tests, 86 Nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs), 256–257, 258t Number needed to screen, 76 Nummular dermatitis, 704, 705f Nursing home patients, treatment for CAP, 211t Nutraceuticals, 1141 drug interactions, 1155t–1159t Nutrient requirements, conditions increasing, 819–824 Nutrition adolescents, 430–431 assessment history, 819–825 laboratory evaluation, 826–827 physical examination, 825–826 current dietary guidance, 818–819 for diabetes mellitus, 737 of elderly patients evaluation, 35 questionnaire, 36f genomics and diet, 840–841 hospitalized patient: decisions, 835–838 infancy through adolescence, 428 infants and toddlers, 428–430 in life cycle, 827–831 during prenatal period, 361–363 in terminally ill patient, 67–68 Nutritional conditions neuropathies, 993 preventive services, 88–90 Nutritional supplementation enteral, 838 parenteral, 838 Nutritional support, in pressure sore management, 43

O Obesity, 89–90 assessment, 804–805 changes in prevalence estimates, 803f demographics, 805–806 determinants, 806–808 management and interventions, 810–817 medical complications, 808–810 overview, 802–804 and risk for PVD, 520–521 Obliterative bronchiolitis, 274b Obsessive-compulsive disorder (OCD), 1041t–1047t, 1058 Obstetrics. See also Gynecology; Pregnancy antepartum fetal surveillance, 382–384 electronic fetal monitoring contractions, 392–393 interpretation of FHR recordings, 389–392

Obstetrics (Continued) intrapartum procedures, 395–399 labor and delivery abnormalities of, 387–389 normal, 384–387 medical risk assessment, 363 multiple gestation, 382 nutrition, 361–363 postpartum hemorrhage, 400–401 preconception counseling, 361 prenatal care first visit, 363–365 follow-up visits, 365–367 prenatal genetic diagnostic testing, 367–368, 1016–1017 puerperium, 399–400 vaginal birth after cesarean, 393–395 woman and child health, 360–361 Obstruction nasal, 320–321 in stridor, 334 Obstructive lung disease, 268–278 acute respiratory failure, 277 asthma, 269–273 chronic bronchial diseases, 278 COPD, 273–277 Obstructive sleep apnea, 333 obesity and, 809 Obstructive sleep apnea syndrome, 445 Occupational exposure to HIV, 250 Occupational lung disease, 292–294 Ocular trauma emergencies, 936 urgent situations, 936–939 Oculomotor nerve (CN III), 960 Office business and management, 122 to improve diabetic outcomes, 754–755 Office care, for dementia patient, 1089–1090 Office procedures anorectal disease, 566–569 basic skills, 551–555 cryotherapy, 563–564 excisions, 562–563 gynecologic, 569–574 incision and drainage of cutaneous abscess, 564–565 lipomas, 565 musculoskeletal, 575–576 neonatal circumcision, 574–575 skin closure, 558–562 surgery of nail and digits, 565–566 wound healing stages of, 556 wound dressings, 558 Office systems and design, 165 Older adults alcohol use disorders among, 1103 headaches, 965 with incontinence, referrals of, 50t prevention of falls, 40f preventive services for, 92 sexuality issues, 1011–1012 Older adults: ophthalmic conditions anterior ischemic optic neuropathy, 956 cataracts, 950–951 diseases of eyelid, 948 dry eye (keratitis sicca), 949–950

Older adults: ophthalmic conditions (Continued) giant cell arteritis (temporal arteritis), 954–955 glaucoma, 955–956 herpes zoster and herpes simplex, 948 myasthenia gravis, 949 ocular changes with aging, 950 optic neuritis, 957 ptosis, 948–949 retina and optic nerve diseases, 951–954 thyroid eye disease (thyroid orbitopathy), 950 TIAs in carotid artery disease, 956–957 uveitis, 951 Olecranon bursitis, 611–612 Olfactory nerve (CN I), 960 Olive leaf, 1142t–1147t Omega-3 fatty acids, 834, 1155t–1159t, 1161t On-the-field assessment, of catastrophic cervical spine injury, 585–586 Onychocryptosis, 565 Onychomycosis, 565, 711 Open neural tube defect, 368t Ophthalmia neonatorum, 930–931 Ophthalmic solutions, for allergic conjunctivitis, 347t Ophthalmology adult, 947–957 ocular trauma, 936–939 pediatric, 939–947 red eye, 928–936 Opiates detection time, 1127t intoxication and withdrawal, 1129 medical management, 1130–1131 pharmacology, 1129 Opioids analgesics, dosing data, 62t–64t for pain control, 60–61 prescribing checklist, 65t Opportunistic infections associated with HIV/AIDS, 284–287 primary prophylaxis, 259t Opportunities for patient education, 161 Oppositional defiant disorder (ODD), 450 Optic chiasm impingement, 757 Optic nerve (CN II) damage, with elevated intraocular pressure, 955–956 diseases, 951–954 examination, 960 Optic neuritis, 957 Optic neuropathy, anterior ischemic, 956 Optimal healing environment, 18–19, 22t Oral cavity acute pharyngitis, 330–332 sleep apnea, 333 snoring, 333 swallowing disorders, 332–333 tonsillitis, 330–332 Oral collagen, for rheumatoid arthritis, 666–667 Oral contraceptives, 473–474 Oral drugs antidiabetics, 739–741 antihypertensives, 487t–489t Oral treatment of PID, 224t

1157

Index Orbital cellulitis, 935 Orgasmic disorders female, 1003–1004 male, 1008 Orlistat, 814–815 Oropharyngeal dysphagia, 332 Orthopedic disorders, obesity and, 810 Orthopedic hardware infections, 239–240 Orthopedics issues ankle and foot, 624–629 elbow, 610–612 fractures, 601–603 knee, 616–624 shoulder, 603–610 wrist and hand, 612–616 Ortolani’s maneuver, 409f Oseltamivir, 213t Osteoarthritis of cervical spine, 635f clinical findings, 655–656 degenerative, of knee, 616–618 NSAIDs for, 667t Osteochondritis dissecans (OCD), 598 Osteomyelitis, 237–239 diabetic foot, 239 Osteoporosis adult nutrition and, 830 in postmenopausal women, 89 USPSTF framework for screening, 75f Otalgia, 305–306, 312b Otitis externa, 309–311 Otitis media acute, 311–313 chronic suppurative, 313 complications, 314–315 with effusion, 313–314 recurrent, 314 Otorhinolaryngology ears, 305–318 emergencies epiglottitis, 300–301 epistaxis, 303–305 foreign bodies, 302–303 peritonsillar abscess, 301–302 sudden sensorineural hearing loss, 302 facial nerve paralysis, 318–319 head and neck trauma, 305 larynx, 333–338 neck, 338–342 nose and paranasal sinuses, 319–330 oral cavity and pharynx, 330–333 Otorrhea, purulent, 313 Otosclerosis, 316 Outcomes improvement, for diabetes, 754–755 Ovarian cancer, 80, 459–460 hereditary, 1019–1020 smoking-related, 1110 Ovarian disorders abnormal puberty, 785–787 amenorrhea, 790–793 delayed puberty, 787–789 infertility, 793–794 normal sexual development, 784–785 polycystic ovary syndrome, 794–796 Overactive bladder, 917 Overflow incontinence, 49 Overuse injuries, 598

1158

Overweight, in childhood, 810–811 Ovulation method of contraception, 472 Oxacillin, 233t Oxybutynin, 51t Oxycodone, 61t dosing data, 62t–64t street names, 1125t Oxygen saturation, 266 Oxytocin, 763

P Paced rhythms, 541–542 Pacemakers, for arrhythmias, 545–549 Packing, anterior or posterior, 304 Pain abdominal, differential diagnosis, 845b in fibromyalgia syndrome, 686 flank, 904 low back, 638–641 pelvic, 464–466 sexual, in females, 1004–1005 Pain control in dying patient, 60–65 for pressure ulcers, 44 Pain disorder, 1040b, 1041t–1043t Pallor, of neonate, 413 Palmar-plantar psoriasis, 698, 700f Palmar-plantar warts, 714–715 Palpation of pedal pulses, 522–525 in pulmonary medicine, 262–263 Palsy Bell’s, 318 progressive supranuclear, 995 Panbronchiolitis, diffuse, 274b Pancreatic disease acute pancreatitis, 861–862 cancer, 863 smoking-related, 1109 chronic pancreatitis, 862–863 elevated amylase and lipase levels due to, 182t Panhypopituitarism, 759 Panic attack, diagnostic criteria, 1066b Panic disorder, 1028t–1029t pharmacologic therapies for, 1075 without agoraphobia, 1067b Pantothenic acid (vitamin B5) nutritional summary, 820t–824t supplements, 1147t–1154t Papillary carcinoma, 774 Papillomatosis, recurrent respiratory, 335 Pap smear, 455–456 Papulopustular rosacea, 701 Paracervical block, 569–574 Paradoxical vocal cord motion, 353 Paragard T380A, 570–571 Paralanguage body language, 150–157 detecting lying, 157 proxemics: spatial factors, 157 and tone of voice, 149 touch, 150 Parallel diagnostic inquiry, 1052–1053 Paralysis facial nerve, 318–319 sleep, 445 vocal cord, 335–337

Paranasal sinuses clinical problems, 320–330 patient history, 319 radiography, 319–320 Paranoid personality disorder, 1041t–1047t, 1054–1055 Paraphimosis, 911 Parasitic infections AIDS-defining illnesses, 252 causing FUO, 241b Parathyroid hormone (PTH), 183 and vitamin D levels, 204 Parental education before discharge, 418–419 Parenteral nutrition, 838 Parenteral treatment of hypertensive emergencies, 491t of PID, 224t Parkinson’s disease, 994–997 Paronychia, 565 Paroxysmal hemicrania, 965 Paroxysmal nocturnal hemoglobinuria (PNH), 885 Paroxysmal sweats, with alcohol withdrawal, 1096t–1097t Partial lens opacities, 945–946 Partnered sexual activity, 1009–1010 Passive smoking, 1114–1115 Patch contraceptive, 474 nicotine, 1119b, 1120 Patellofemoral syndrome, 618–619 Pathogenesis of diabetes mellitus, 731–732 of diabetic ketoacidosis, 745 of rheumatic and other musculoskeletal diseases, 650–652 Pathogens in acute diarrhea, 846t of bacterial meningitis, 977t, 982t Pathologic coping styles, 1033b Pathophysiology of CHF, 508–509 of diabetes mellitus, 733–734 of HIV, 250 of peripheral neuropathies, 987 of PVD, 520–521 Patient care and information technology, 120–121 successful, essential components of, 146 Patient-centered medical home, 15, 18t and psychosocial issues, 31 Patient education model of health behavior change, 161–162 opportunities for, 161 planning for, 163–165 principles of, 161 rationale, 160–161 Patient Health Questionnaire 9, 1065 Patient history crisis and selective past history, 1027–1029 for delirium etiology, 1080–1081 for dementia, 1084 in diagnosing PVD, 522 of dizziness, 306b in evaluation of CHF, 509 at first prenatal visit, 364b HIV-specific, 255t

Index Patient history (Continued) in initial evaluation of falls in elderly patients, 38t nose and paranasal sinuses, 319 nutrition assessment, 819–825 for peripheral neuropathies, 988 PPE cardiovascular questions, 579b prior to office procedures, 551 in pulmonary medicine, 262–263 sexual history, 1000–1002 Patient-oriented evidence that matters (POEM), 126 Patient participation, in interview process, 169 Patient preferences, clinical problem solving and, 127–129 Patient relationships, management of, 121 Patient satisfaction, 4, 147–148 Pattern recognition of arrhythmias atrial rhythms, 536–538 disorders of AV node conduction, 540 junctional rhythms, 538–539 paced rhythms, 541–542 ventricular rhythms, 541 Patterns of inheritance, 1015t, 1019t Pau d’arco, 1142t–1147t Peak expiratory flow rate (PEFR), 263 Peak flow monitoring, for asthma, 348–349 Pediatric ophthalmology cataracts, 945–946 headaches, 944–945 learning disabilities and the eye, 945 red eye in older children, 932–936 refractive errors and color vision, 943–944 retinoblastoma, 946–947 strabismus and amblyopia, 941–943 testing visual acuity, 940–941 vision evaluation, in first four months, 939–940 vision screening and ocular examination, 940 Pediculosis capitis (head lice), 717–718 Pediculosis corporis (body lice), 718 Pediculosis pubis, 225 Pelvic floor muscle exercises, 50 Pelvic inflammatory disease (PID), 222, 224, 464 Pelvic mass, 459–460 Pelvic pain acute, 464–466 chronic, 464–466 Pelvic rocks, 641f Penile cancers, 925 Pentazocine, 61 in elderly, 46t Peppermint oil, 1161t Peptic ulcer disease, 848–851 Percussion, in pulmonary medicine, 262–263 Perforations, traumatic tympanic membrane, 315 Perilymph fistula, 308 Perimenopause, abnormal vaginal bleeding in, 458–459 Periodic health examination, rethinking, 95 Peripheral blood increased number of platelets in, 892f normal WBC counts, 889t

Peripheral neuropathies anatomy, 987 classification, 987 clinical pathophysiology, 987 laboratory evaluation, 988–989 mononeuropathies, 986, 989–992 polyneuropathies, 992–994 Peripheral vascular disease (PVD) asymptomatic disease, 519 coexisting vascular disease, 521 critical limb ischemia, 519–520 epidemiology, 518–519 history, 522 intermittent claudication, 519 noninvasive testing, 525–529 physical examination, 522–529 risk factors, 520–521 smoking as risk factor, 1112 therapy, 529–530 Perirectal abscesses, 568f Peritonitis, spontaneous bacterial, 242–243 Peritonsillar abscess, 301–302 Peroneal neuropathy, 991 Personal control, 28 Personality, five-factor model of, 26t Personality disorders categorical and dimensional approaches to, 1038 comorbidity, 1039–1040 interventions for, 1054–1059 management principles for difficult patients, 1049–1052 previous, 1027 vs. personality style, 1038 Personalized care, 6–7 Pessaries, 50 Petechiae, 893 in neonate, 413 Peyronie’s disease, 911 pH, of urine, 900–901 Phacoemulsification, 951 Pharmacodynamics, and aging, 45 Pharmacokinetics, and aging, 45 Pharmacologic therapies for acute diarrhea, 846t for ADHD, 448–450 for Alzheimer’s disease, 1085–1086 for CHF, 510–513 for dementia, 972–973 for diabetes mellitus, 739–741 for incontinence in elderly patients, 51–52 for migraine, 963 for osteoarthritis, 657–658 for Parkinson’s disease, 995–997 for PVD, 529–530 for seizures, 974–975 for smoking cessation, 1117–1121 for somatic patient, 1054 for stable angina, 501–503 for stroke, 968 for unstable angina, 504–505 Pharyngitis, 201 acute, 330–332 Phencyclidine (PCP) detection time, 1127t intoxication and withdrawal symptoms, 1130t street names, 1125t

Phenothiazines, effect on lipid values, 195t Phenylbutazone, in elderly, 46t Pheochromocytoma, 783–784 Phimosis, 911 Phobia, related to trauma, 1028t–1029t Phosphate disturbances hyperphosphatemia, 799 hypophosphatemia, 800 Phosphatidylserine, 1155t–1159t Phosphodiesterase-5 inhibitors, 1006t oral, 916t Phosphorus laboratory test, 196–197 nutritional summary, 820t–824t Photorefractive tests, 941 Phototherapy, for neonatal jaundice, 416, 417b Physeal injuries, in pediatric athletes, 598 Physical abuse, of elderly, 41t Physical activity counseling on, 90 for obesity, 814 Physical examination abdomen, 844 for alcohol use disorders, 1094 of cervical spine, 631–634 for delirium, 1080–1081 for dementia, 1084 HIV-specific, 256t for incontinence in elderly patients, 49–50 initial evaluation of falls in elderly patients, 38t larynx, 333–334 of newborn, 406–410 of skin condition, 690–692 for nutritional status, 825–826 for patient presenting with joint pain, 650 in pulmonary medicine, 262–263 for PVD, 522–529 for red eye, 928–930 for rheumatoid arthritis, 660–661 sports physical, 578–580 of thoracolumbar spine, 636–637 of urinary tract, 899–900 for vertigo, 306 for visits throughout pregnancy, 365t Physical maturity, 410b, 411f Physicians with alcohol use disorders, 1103 attitudes toward dying patient, 54–55 belief in primary prevention, 109–110 as catalysts for patient behavior change, 93 of the future, 138t personal appearance, 146–147 primary care, 6 reactions to difficult patients, 1044t–1047t, 1048–1049 writing own patient education material, 164 Physician satisfaction, 4 Pills emergency contraceptive, 477 progestin-only (minipill), 475 Pilonidal cyst, 569 Pituitary disorders approach to, 757 Cushing’s disease, 762–763 hyperfunctioning pituitary adenomas, 761–762

1159

Index Pituitary disorders (Continued) hypopituitarism, 757–761 hypothalamic-pituitary axis, 756–757 posterior, 763–767 Pityriasis, 694 Pityriasis rosea, 700–701 Placebo effect, 18–19 Placenta accreta, 381–382 Placenta increta, 381–382 Placental separation, 385–386 Placenta percreta, 381–382 Placenta previa, 380–381 Plantar fasciitis, 628–629 Plaque, atheromatous, 479 Plaque psoriasis, 698, 699f Plasma proteins, 827 Plastibell, 575 Platelet count, 187t, 188 Platelet disorders of platelet function, 895–896 thrombocytopenia, 892–895 thrombocytosis, 895 Platelet function disorders, 895–896 Plavix. See Clopidogrel Pleomorphic adenoma, 341 Pleural diseases, 297–298 pleural effusion, 263t Pleurisy, in SLE, 680 PLISSIT model, for approaching sexual problems, 1002b Plummer-Vinson syndrome, 332 Pneumococcal conjugate vaccine (PCV7), 439–440 Pneumococcal pneumonia, 281 Pneumoconioses, occupational, 293 Pneumocystis jiroveci (carinii) pneumonia, 259t, 284–285 Pneumonia community-acquired, 209, 211t epidemiology, 279 and HIV/AIDS, 252 in newborn, 413–414 pneumonia severity index (PSI), 210 Pneumonitis, hypersensitivity, 293–294 Pneumothorax, 263t, 297–298, 593 Point of care decision making, organizing information for, 122 using evidence at, 116–119 Poliovirus vaccine, 438 Politician’s handshake, 150f Polyarticular symptoms, 650f Polycystic ovary syndrome, 794–796, 797f, 808 Polycythemia, 187, 188t, 887–888 Polymotor-sensory neuropathy, 750 Polymyalgia rheumatica, 683 Polyneuropathies, 992–994 Polyps cervical, removal of, 573 nasal, 321–322, 329, 346 Polyurethane wound dressings, 45t Polyuria, 764 Pompholyx, 703–704 Population, by age and gender, 34t Portion control, 813 Positive angle kappa, 944f Positive emotional states, 26

1160

Positive predictive value (PPV), of PSA for prostate cancer, 199t Positron emission tomography (PET), of chest, 265–266 Posterior cruciate ligament injuries, 622–623 Posterior interosseous syndrome, 991 Posterior lenticonus, 946 Posterior packing, for epistaxis, 304 Posterior pituitary disorders arginine vasopressin, 763 central diabetes insipidus, 764–765 Posterolateral ligament complex injuries, 621 Postherpetic neuralgia, 214 Postmenopause, abnormal vaginal bleeding in, 459 Postoperative care, of diabetic patients, 748 Postovulation method of contraception, 473 Postpartum gestational diabetes, 748 Postpartum hemorrhage, 400–401 Postpartum pituitary necrosis, 758 Posttraumatic stress disorder (PTSD), 1028t–1029t, 1036 Postural dizziness, 985 Postvoid residual measurement, 902 Potassium abnormal, causes of, 198t laboratory test, 197 nutritional summary, 820t–824t in treatment of diabetic ketoacidosis, 746 Pott’s disease, 677 Power, statistical, 115–116 Practice content, 14–15 Pramlintide, 741 Prasugrel, 507–508 Prayer, 141 Precipitating factors for asthma, 348 for delirium, 1080b Precision, in laboratory testing, 176 Precocious puberty, 785–787 Preconception counseling, 361, 402–403 Predictive value, of laboratory test, 178 Preeclampsia, 379 Preening gestures, 156 Preexcitation syndrome, 542–543 Pregabalin, 686 Pregnancy alcohol abuse and, 1102 antepartum fetal surveillance, 382–384 complications of early labor, 375–377 drug and chemical exposures during, 368–369 effect on ESR, 190t electronic fetal monitoring, 389–393 gestational diabetes mellitus in, 747–748 infections in, 369–371 intrapartum procedures, 395–396 labor and delivery abnormalities of, 387–389 normal, 384–387 laboratory tests, 197 late, complications of, 377–382 medical disorders in, 371–375 multiple gestation, 382 nutrition in, 827–828 platelet counts in, 894 postpartum hemorrhage, 400–401

Pregnancy (Continued) preventive services for pregnant women, 91–92 puerperium, 399–400 substance use disorders and, 1133 thyroid disease in, 775–776 type 1 diabetic, 748 type 2 diabetic, 748 UTI in, 226–227 vaginal birth after cesarean, 393–395 Premature atrial contractions, 537 Premature (rapid) ejaculation, 915, 1007–1008 Prenatal care first visit, 363–365 follow-up visits, 365–367 Preoperative clearance, of diabetic patients, 748 Preparticipation physical examination (PPE), 578–580 Presbycusis, 316 Prescribing drugs for difficult patients, 1051–1052 for elderly patients, 47 Preseptal cellulitis, 935 Pressure ulcers in elderly patients classification, 42 infection control, 44 nutritional support, 43 risk factors, 42–43 Presyncopal lightheadedness, 985t Preterm labor, 377–378 Prevalence of alcohol use disorders, 1092 of anemia, 879–880 of diabetes mellitus, 732 plotted against predictive value, 178 statistical expression, 76 Prevention of AIDS-related infections, 286–287 of alcohol abuse, 1104 of Alzheimer’s disease, 1086–1087 of bacterial meningitis, 980–981 of delirium, 1081 of endocarditis, 518 evidence-based, key concepts, 73–76 of falls, in older persons, 40f focus on heart disease, 100–103 of lung cancer, 292 of pneumonia, 281–282 statistical concepts in, 76–77 of STIs, 219 of tick-borne disease, 231 Preventive health care counseling, 92–94 key concepts in evidence-based prevention, 73–76 preventive services for children and adolescents, 90–91 by disease category, 77–90 for older adults, 92 for pregnant women, 91–92 statistical concepts, 76–77 systems change, 94–95 Prezista. See Darunavir Primary adrenal insufficiency, 778–779 Primary aldosteronism, 782 Primary amenorrhea, 790–792 diagnostic algorithm, 794f

Index Primary care definition, 5–6 genetics in, 1018–1021 of patients with substance use disorders, 1132–1133 sports medicine, 577–578 Primary hyperparathyroidism, 796, 798t Primary prevention and change in disease-specific mortality, 102t focus on lifestyle, 103–108 physician’s belief in, 109–110 Primary prevention services, 74 Primary Sjögren’s syndrome, 682b Primary syphilis, 220–221, 221t Printed materials, in patient education, 163–164 Probenecid, 670 Probiotics, 1155t–1159t, 1161t Problematic alliance, attending to, 1049 Problem-focused treatment, of crisis, 1031–1032 Procedure room, 552–553 Progestin, effect on lipid values, 195t Progestin-only contraceptives, 474–475 Prognosticating, and terminal illness, 57 Progressive supranuclear palsy, 995 Progressive systemic sclerosis, 297 Prolactin, elevated serum levels, 760 Prolactinomas, 761–762 Prolapse of cervical disk, 635f mitral valve, 517–518 Proliferative diabetic retinopathy, 953–954 Proliferative phase of healing, 556 PROP-1 gene, 758 Prophylaxis for bacterial endocarditis, 514t in bacterial meningitis, 980–981 for migraine, 963–964 of recurrent gout, 670 Propoxyphene detection time, 1127t dosing data, 62t–64t in elderly, 46t Prostaglandin E2 for cervical ripening, 386 in treatment of ED, 1006–1007 Prostate cancer, 81, 925–926 Prostate-specific antigen (PSA), 197–198, 925 noncancer factors influencing, 199t Prostatitis, 227–228 bacterial, 919 chronic nonbacterial, 913–914 Protease inhibitors (PIs), 256–257 Protein dietary intake, in diabetes, 834 nutritional summary, 820t–824t in urine, 901 Protein status assessment, 826–827 Proteinuria, 908 Prothrombin time (PT), 185 Protraction of dying process, 59 Proxemics, 157 Pruritus, management of, 692–693 Pseudocysts, 864f Pseudogout, 670–672 Pseudohyperkalemia, 198t Pseudohyponatremia, 200

Pseudostrabismus, 942 Psoriasis, 698–700 Psoriatic arthritis, 674–675, 698 Psychiatric disorders and alcohol dependency: comorbidities, 1099–1100 medications for symptoms of, 1035–1036 related to trauma, 1028t–1029t Psychiatric evaluation, for alcohol abuse, 1094 Psychiatric symptoms, accompanying dementia, 1089 Psychological assessment, of elderly patients, 35 Psychological factors, in biopsychosocial model, 25–26 Psychological impact of obesity, 810 Psychosis, brief, 1028t–1029t Psychosocial data collection, 29 interventions utilizing, 29–30 Psychosocial factors, of GI disease, 843–844 Psychosocial issues biopsychosocial model, 25–27 care responsive to, 24 clinical practice and, 29–30 ethnomedical cultural model, 28–29 evidence-based practice, 30–31 life span perspective, 28 patient-centered medical home and, 31 stress and coping model, 27–28 systems approach, 27 Psychosocial stages (Erikson), 432t Psychosocial therapy, for ADHD, 448 Psychotherapy basic techniques, 1049–1050 for depression and anxiety, 1077 for somatic patient, 1054 Pthirus pubis (crab lice), 718 Ptosis, 948–949 Pubarche, isolated precocious, 786 Puberty abnormal, 785–787 delayed, 787–789 growth and development in, 424–425 PubMed, 117 Pudendal neuropathy, 594 Puerperium, 399–400 Pulley sutures, 561 Pulmonary disease, obesity and, 809 Pulmonary embolism, 287–288 Pulmonary fibrosis, idiopathic, 296f Pulmonary function changes in pregnancy, 372t testing, 263–264 Pulmonary hypertension, 289–290 Pulmonary involvement, with rheumatoid arthritis, 661 Pulmonary medicine bronchoscopy, 266 chest radiography, 264–266 cough, 268 diagnostic tools, history and physical examination, 262–263 measurement of blood gases, 266 pulmonary complications of sickle cell disease, 290–291 pulmonary function testing, 263–264 shortness of breath, 266–267

Pulmonary tuberculosis, treatment regimens, 217t Pulmonic valve disease, 518 Pulse oximetry, transcutaneous, 266 Pupillary change, with blunt eye injury, 938 Purified protein derivative (PPD) LTBI and, 216–218 and treatment of pneumonia, 283 Purpura Henoch-Schönlein, 688 idiopathic thrombocytopenic, 893–894 thrombotic thrombocytopenic, 894–895 Push enteroscopy, 869–870 Pustular psoriasis, 698, 700f Pycnogenol, 1142t–1147t Pyelonephritis, 226 in pregnancy, 375 Pyogenic granuloma, 723–724 Pyrimidine synthesis inhibitor, for rheumatoid arthritis, 664t–665t

Q Qigong, 143t Quality of care, 9–10 improvement, 122 Quality of life, 53–54 Quantiferon-TB Gold test, 218 Quercetin, 1155t–1159t Questionnaires geriatric health questionnaire, 37f Patient Health Questionnaire 9, 1065 Questions about alcohol use, 1093–1094 for detailed sexual history, 1002b focusing, in clinical problem solving, 125 Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR), 1065

R Rabies postexposure treatment, 237 Radial neuropathy, 991 Radiculopathy, cervical, 634–636 Radiography chest for COPD, 275 in pulmonary medicine, 264–266 to evaluate syndesmosis, 626–627 of larynx, 334 of nose and paranasal sinuses, 319–320 Raltegravir, 258t Ramsay Hunt syndrome, 318 Randomized controlled trials (RCTs), in HRT, 113–114 Range of motion (ROM), 606–607, 617, 633f, 637t Ranolazine, for stable angina, 502 Ranulas, 339 Rapid-acting synthetic insulins, 742t Rapid antigen detection test (RADT), 201–202 Rapid plasma reagin (RPR) test, 202, 220–221 Rapport communication, 148–159 eye contact and, 146 patient satisfaction and, 147–148 respect, 147

1161

Index Rash erythema migrans, 676 heliotrope, of dermatomyositis, 722f in Lyme disease, 230f Rationale for patient education, 160–161 Raynaud’s phenomenon, 684 Reactive arthritis, 673–674 Reactive lymph nodes, 340 Reality testing, by difficult patient, 1050 Receiver operating characteristic (ROC) curve, 178, 179f Recommended daily allowance (RDA), 841 Rectal bleeding, massive acute, 871t Rectal cancer, smoking-related, 1110 Recurrent corneal herpetic infections, 935 Recurrent gout, 670 Recurrent meningitis, 981 Recurrent otitis media, 314 Recurrent respiratory papillomatosis, 335 Recurrent UTI, 227, 922 Red blood cells (RBCs) disorders, 878–888 anemia, 879–887 myeloproliferative, 888 polycythemia, 887–888 laboratory test, 187 99mTc pertechnetate-labeled, 868 in urine, 901 Red clover, 1142t–1147t Red eye as blunt eye injury, 938 physical examination, 928–930 signs and symptoms, 928 Red eye in adults and older children, 932–936 allergic conjunctivitis, 934 angle-closure glaucoma, 936 bacterial conjunctivitis, 933–934 blepharitis, 933 chalazion, 933 corneal herpetic infections, 935 corneal ulcers, 935–936 iritis, 935 orbital cellulitis, 935 stye, 933 subconjunctival hemorrhage, 934 viral conjunctivitis, 934 Red eye in infants acute dacryocystitis, 931 bacterial conjunctivitis, 931 chlamydial infection, 931 chronic dacryocystitis, 932 congenital glaucoma, 932 ophthalmia neonatorum, 930–931 Red reflex test, 941–942 Reduced nicotinamide adenine dinucleotide (NADH), 1155t–1159t Reepithelialization, 557f Reference materials, on HRT, 117t Referrals of older patient with incontinence, 50t to rheumatologist, 655 Reflexes examination of, 961 newborn, 407–408 Reflux laryngitis, 338 Refractive error correction in adults, 947 in children, 943–944

1162

Refractive errors, 943–944 Refusal to sleep, 444 Regenerative phase of healing, 556 Registries, populations tracked via, 121 Regurgitation aortic valve, 514–515 infantile, 844–847 mitral, 516–517 Reinforcement, in patient education, 161 Reiter’s syndrome, 673–674 Relapse prevention in behavior change, 839 in smoking cessation, 1121 Relationship healing, in medical home, 19–20 patient, management of, 121 Relative risk ratio (RRR), 129 Relaxation, as healthy lifestyle factor, 105–106 Relevance, of patient education, 161 Religious issues discussing at end-of-life, 59 in interview process, 170–171 Remodeling phase of healing, 556 Renal cancers, 926 Renal disease renal calculi, 918 SLE-induced, 679 Renal failure, and CEA level, 184t Renal interstitial syndromes, 751 Renal protection, in diabetic care, 751–752 Renin-angiotensin-aldosterone system, 509f Reporting requirements for cases of intimate partner violence, 1034–1035 for elder abuse, 42 Rescriptor. See Delavirdine mesylate Reserpine, in elderly, 46t Resistant body position, 155f Resolution of acute crisis, 1027 Resorptive phase of healing, 556 Respect, and establishing rapport, 147 Respiratory avoidance response, 156 Respiratory distress syndrome (RDS), in newborn, 413 Respiratory embarrassment, 305 Respiratory system, of neonate, 412 Responsibility of physician, continuing, 7–12 Resting energy expenditure, 837 Restraint, therapeutic, 59 Resuscitation of infant born through meconium-stained amniotic fluid, 406 neonatal, 404–406 Resynchronization, cardiac, 548–549 Retavase, 507t Reticulocyte count, 187t, 881 Retina diseases, 951–954 Retinal detachment, 939, 954 total, 947f Retinitis, CMV, 259t Retinoblastoma, 946–947 Retinoids, effect on lipid values, 195t Retinol-binding protein (RBP), 827 Retinopathy diabetic, 750, 953–954 with exercise in diabetes mellitus, 738 hypertensive, 953 Retractions, in neonate, 412

Retrospective control, 28 Return to play, following concussion in sports, 583–584 Revascularization, for PVD, 530 Reverse cholesterol transport, 480f Reverse transcriptase inhibitors (RTIs), 251 Reyataz. See Atazanavir Rhabdomyosarcoma, 340 Rh(D) blood typing, 399 Rheumatic diseases in children, 687–688 crystal arthropathies, 668–672 fibromyalgia syndrome, 685–687 infectious arthritis, 675–677 osteoarthritis, 655–659 rheumatic fever, 677–678 rheumatoid arthritis, 659–668 Sjögren’s syndrome, 681–682 spondyloarthropathies, 672–675 systemic lupus erythematosus, 678–681 vasculitic syndromes, 682–685 Rheumatism, nonarticular, 688 Rheumatoid arthritis diagnosis and history, 659–660 juvenile, 687 laboratory studies, 661 lung manifestations of, 297 monitoring arthritic activity, 667–668 physical examination, 660–661 surgery and other therapies, 666–667 treatment, 661–666 Rheumatoid factor, laboratory test, 199 Rheumatology evaluation of joint symptoms, 648–650 laboratory studies, 652–655 musculoskeletal disease pathogenesis, 650–652 Rhinitis allergic, 322–323, 344–346 atrophic, 324 idiopathic, 323 nonallergic, 346 vasomotor, 323 Rhinitis medicamentosa, 323–324 Rhythms biologic, affecting laboratory results, 177t classification of, 545b ECG analysis, 536 Ribose, 1155t–1159t Rickettsia rickettsii, 228 Rimantadine, 213t Ring block, 554 Risk assessment for behavior risk factors, 93 medical, in preconception period, 363 Risk factors for acute otitis media, 312b for AIDS-related infections, 284, 286t for asthma, 269 for atherogenic serum lipoproteins, 481 cardiovascular, for metabolic syndrome, 492–494 for cardiovascular disease, 82f for CHF, modification, 509–510 for COPD, 273–274 for delayed-onset hearing loss in young children, 426b for delirium, 1080b

Index Risk factors (Continued) for development of delirium, 970b for elder abuse, 39 of exercise, in diabetes mellitus, 738 for falls in elderly patients, 38 for fungal infections of lung, 287 high-risk indicators in unstable angina, 504b for HIV, 249–250 for interstitial lung diseases, 296 for lung cancer, 291 for lung disease, 261–262 maternal, teratogenic, 403b for pressure ulcers, 42–43 for preterm labor, 377b for pulmonary embolism, 288–289 for pulmonary hypertension, 289–290 for PVD management, 529 nontraditional, 521 traditional, 520–521 for sarcoidosis, 295 as statistical concept in prevention, 76–77 for stroke, 966–967 for TB, 282 Ritalin. See Methylphenidate Ritonavir, 258t Ritter LISTEN paradigm, 167t Rocky Mountain spotted fever, 228, 229t Rohypnol. See Flunitrazepam Rooting reflex, 407 Rosacea, 701 Roseola infantum, 697 Rotator cuff disease, 604–608 Rotavirus vaccine, 439 Roux-en-Y gastric bypass, 816f Roxicodone. See Oxycodone Rubber band ligation, 567f Rubella, 697 in pregnancy, 370 vaccine, 438 Running sutures, 561 Rupture, Achilles tendon, 628 Rural/urban differences, in obesity prevalence, 806

S Safety home, for neonate, 418–419 planning, for victims of intimate partner violence, 1034, 1035b Salivary gland disorders, 341 Salmon, Thomas, 1022 Salter–Harris type fractures, 602–603 Salt restriction, dietary, 512 Sanctura. See Trospium Sandimmune. See Cyclosporine Saquinavir mesylate, 258t Sarcoidosis, 294–295, 340–341, 722–723 Satisfaction patient, 4, 147–148 physician, 4 Saw palmetto, 1142t–1147t Scabies, 225, 716–717 Scalp psoriasis, 698, 699f Scaphoid fractures, 616 Scapholunate sprains, 614–615

Scars, hypertropic, 558 Schedule of immunizations, 438 Schilling test, 884 Schistocytes, 885f Schizoid personality disorder, 1041t–1047t, 1055 Schizotypal personality disorder, 1041t–1047t, 1055 School-age child, assessing development in, 436–437 Schwannomas, vestibular, 316 Sciatic neuropathy, 991 Scleroderma renal crisis, 684–685 Sclerosing basal cell carcinoma, 727f Sclerosis progressive systemic, 297 systemic, 684–685 Sclerotherapy, for hemorrhoids, 567 Scoliosis, 646 Screening for alcohol use disorders, 1092–1094 for anxiety disorders, 1066–1067 audiology, of newborn, 410 for autism, 435–436 for bipolar disorder, 1065–1066 cardiovascular, in PPE: limitations, 579–580 for colorectal cancer, 874b for depression, 1065 developmental, in young children, 433–435 for elder abuse, 40–41 elderly patients, for hearing loss, 35 for falls in elderly patients, 38 genetic, 362b for gestational diabetes, 374t for gestational diabetes mellitus, 747 in healthy children, 425–427 for HIV, 254b for intimate partner violence, 1033 maternal biochemical, 367–368 for primary aldosteronism, 782f for prostate cancer, 926b STIs, 219t for substance use disorders, 1125–1127 for thyroid disease, 776–777 vision, 426–427, 940 in well-woman examination, 455 WHO criteria for screening test, 74t Screening test accuracy for abdominal aortic aneurysm, 83 for alcohol abuse, 85 for breast cancer, 79 for cervical cancer, 79 for CHD, 83 for chlamydial infection, 86 for colorectal cancer, 77 for depression, 85 for diabetes mellitus type 2, 88 expressing, 76 for gonorrheal infection, 87 for healthy diet counseling, 90 for HIV, 88 for hyperlipidemia, 82 for hypertension, 81 for lung cancer, 80 for obesity, 89 for osteoporosis, 89 for ovarian cancer, 80 for prostate cancer, 81

Scrofula, 340 Search engines, 117 Seborrhea, 698 Seborrheic keratosis, 723 Secondary adrenal insufficiency, 759, 779–780 Secondary amenorrhea, 792–793 Secondary pharmacologic therapy, of STEMI, 508b Secondary prevention and change in disease-specific mortality, 102t of heart disease, 101 Secondary prevention services, 74 Secondary Sjögren’s syndrome, 682b Secondary syphilis, 220, 221t Second-degree AV block, 540 Second-generation antihistamines, 345t Secondhand smoke, 1114–1115 Second-line medications, for smoking cessation, 1121 Second primary/recurrent cancers, smoking-related, 1110 Second stage of labor, 384–385 abnormalities of, 388 Sedation, 555 Sedative-hypnotics, intoxication and withdrawal, 1130 Seizures alcohol withdrawal, 1095b febrile, 973–974 initial diagnostic evaluation, 974 pharmacologic therapy, 974–975 status epilepticus, 975 Selective serotonin (5-HT) agonists, 963t Selective serotonin reuptake inhibitors (SSRIs), 65, 1007–1008, 1070, 1071t, 1074 Selenium nutritional summary, 820t–824t supplements, 1147t–1154t Self-care, importance of, 19 Self-concept, sexual, 1000 Self-defeating personality disorder, 1041t–1047t, 1058–1059 Self-motivation, basic steps toward, 109 Self-neglect, by elderly, 41t Selzentry. See Maraviroc Sense of control, by dying patient, 58–59 Sensitivity of laboratory test, 177 Sensorineural hearing loss, 316b Sensory changes, in peripheral neuropathies, 987 Sensory examination, 961 Sepsis, group B streptococcal, in newborn, 413 Septic arthritis, 240, 675–676 Sequelae of crisis, 1027 Serologic tests for celiac disease, 873 for hepatitis, 192–193 for viral hepatitis, 859t Serotonin-norepinephrine reuptake inhibitors (SNRIs), 1070–1071, 1074 Serotonin syndrome, 814 Serum-ascites albumin gradient (SAAG), 180 Serum creatinine, 45 and chronic kidney disease, 913t Severe persistent asthma, 352 Severity of asthma, 349f–350f Sexual abuse, of elderly, 41t

1163

Index Sexual development, normal, 784–785 Sexually transmitted infections (STIs), 218–222 chancroid, 222, 919 ectoparasites, 225 genital ulcers, 219 gonorrhea, 920 herpes genitalis, 920 HPV, 224–225, 920 nongonococcal urethritis, 920 PID, 224 syphilis, 920–921 urethritis and cervicitis, 222–224 Sexual maturity stages, in boys and girls, 425t Sexual orientation spectrum among adolescents, 1010–1011 care of lesbian, gay, and bisexual patients, 1008 gender identity and expression, 1008–1009 transgender health care, 1009 Sexual pain disorders in females, 1004–1005 Sexual self-concept, 1000 Shaken baby syndrome, 419, 939 Shared decision making, 127–128 Sharp debridement, for pressure ulcers, 44 Sheehan’s syndrome, 758 Shingles, 213–214, 714 Shin pain, 596–597 Short-acting human insulin, 742t Shortness of breath, 266–267 Short stature in children, 422b, 423–424 Shoulder clavicular complex injuries, 603–604 dystocia, 388–389 impingement, and rotator cuff disease, 604–608 injection into, 576 instability, 608–610 Sialoadenitis, acute, 341 Sialolithiasis, 341 Sibutramine, 814 Sick euthyroid syndrome, 774–775 Sickle cell anemia clinical diagnosis, 886–887 pulmonary complications, 290–291 treatment, 887 Sickle cell trait, 887 and sudden death, 594 Sick sinus syndrome, 542 Side bending, 641f weighted, 643f Side effects of antidepressants, 1071t of Parkinson’s disease medications, 996t Sideline management, in sports concussion, 583 Sigmoid diverticula, 872f Sigmoidoscopy, flexible, 874–875 Signs auscultatory, of mitral stenosis, 515–516 of elder abuse, 41t skin, of systemic disease, 720–723 Signs and symptoms of anaphylaxis, 354t of concern, in neonate, 410–415 of concussion in sports, 582–583 of lymphadenopathy, 897t of melanoma, 729t musculoskeletal, evaluation of, 648–650

1164

Signs and symptoms (Continued) of Parkinson’s disease, 995 of red eye, 928 in relation to polycystic ovary syndrome, 795t Sildenafil, 1006t Silence conspiracy of, 57 timing of, 159 Silver (colloidal), 1147t–1154t Sincerity, conveying, 154 Single-gene diseases, 1019t Sinoatrial block, 537f–538f Sinus arrhythmia, 536 Sinusitis acute, 325–327 chronic, 327–328 complications, 325 failure of medical treatment, 328 pediatric, 328–329 underlying cause of, 324 Sinus node complex, 531–533 Sinusoidal patterns, FHR, 392 Sit-ups, modified, 643f Sjögren’s syndrome, 341, 681–682 Skeleton, of newborn, 409–410 Skin loss, due to pressure ulcers, 42 of neonate, 407 preparation for office procedures, 551 primary and secondary lesions, 691t Skin and soft tissue infections (SSTIs), 232, 233t–234t Skin closure complications of, 561–562 principles of, 558–562 skin tension on closure, 559 skin tension orientation, 559 suture placement, 560–561 tissue adhesive, 559–560 Z-plasty, 561 Skin hook, 552f Skin tension on closure, 559 orientation, 559 Sleep apnea, 298 obstructive, 333 obesity and, 809 Sleep deprivation, 445 Sleep optimization, 1081b Sleep position, of neonate, 418 Sleep problems, in children and adolescents, 443–445 Sling procedure, 52 Slow-release drugs, morphine, 61t Smile, in body language, 152–153 Smokeless tobacco, 1114 Smoking cigars, 1113 electronic cigarettes, 1113 filtered cigarettes, 1113 and mental health, 1116 passive, 1114–1115 and preferred contraceptive options, 470t smokeless tobacco, 1114 Smoking: health risks cancer, 1106–1110 cardiovascular disease, 498–499, 1111–1112

Smoking: health risks (Continued) COPD, 273–274, 1110 diabetes mellitus, 1112 lung disease, 261–262 macular degeneration, 1113 PVD, 520, 1112 stroke, 966 Smoking cessation behavior change, 1117 and obesity, 807 pharmacotherapy, 1117–1121 questions to ask patient, 1116 significant barriers to, 1116 stages of change, 1117 strategies for, 262b Smooth muscle spasm co-analgesics for, 66t drug therapy, 65 Snoring, 333 Social assessment, of elderly patients, 35–36 Social cognitive theory, 94t Social factors, in biopsychosocial model, 26 Social issues, in genetic testing, 1018 Social support, 26 of patient in crisis, 1029 Socioeconomic status, and obesity, 805 Sodium laboratory test, 199–201 nutritional summary, 820t–824t Sodium bicarbonate, and ketoacidosis crisis, 746 Sodium glucose-linked transporter protein (SGLT), 741 Solid extract, herbal formulation, 1143t Solifenacin, 51t Solutions, ophthalmic, 347t Somatization disorder, 1028t–1029t, 1040b, 1044t–1047t interventions for, 1056–1058 strategic principles for working with somatic patients, 1052–1054 Somatizing patient, in interview process, 174 Somatoform disorders comorbidity, 1039–1040 coping styles, 1041t–1043t vs. unexplained physical symptoms, 1038–1040 Sonography diagnostic, 396–397 for ectopic pregnancy, 375–376 in placenta previa, 381 for pregnancy dating, 364–365 Soy, 1142t–1147t Specialty development of, 4–5 percent distribution of office visits by, 15f Specific gravity, 900 Specificity of laboratory result, 177 Specimen preparation, for urinalysis, 900 Spermatoceles, 911 Spermicides, 472 Spinal accessory nerve (CN XI), 960 Spinal cord, 632f Spinal stenosis, 645–646 Spiritual issues discussing at end-of-life, 59 in interview process, 170–171 Spirituality, and CAM, 140–141

Index Spirometry, in diagnosis of asthma, 348 Spirulina, 1142t–1147t Spondyloarthropathies ankylosing spondylitis, 672–673 in children, 687 enteropathic arthropathy, 675 psoriatic arthritis, 674–675 reactive arthritis, 673–674 Spondylolysis, in athletes, 594 Spontaneous abortion, 376–377 Spontaneous bacterial peritonitis, 242–243 Sports medicine cardiac disorders in athletes, 580–582 cervical spine injuries, 584–586 concussion in sports, 582–584 dermatology, 591–592 environmental influences, 586 female athlete: special concerns for, 598–600 gastrointestinal problems, 594 genitourinary problems, 594 hematologic problems, 593–594 infectious disease, 590–591 muscle and tendon injuries, 594–596 pediatric athlete, 597–598 preparticipation physical examination, 578–580 primary care, 577–578 pulmonary problems, 592–593 shin pain, 596–597 spondylolysis, 594 stress fractures, 597 trauma to teeth, face, and eyes, 588–590 Sprains ankle, 624–627 cervical spine, 634 sports injuries, 584 scapholunate, 614–615 Squamous cell carcinoma, 727–728 Squeeze test, 626, 627f St. Anthony’s fire (erysipelas), 706 St. John’s wort, 1161t, 1142t–1147t Stable angina mechanical and revascularization strategies, 503 noninvasive testing, 499–501 pharmacologic management, 501–503 Stages of change, 94t in alcohol addiction, 1098 in model of health behavior change, 161–162 in smoking cessation, 1117 Stages of healing, 556 Stages of labor, 384–385 Stages of primary gout, 668–670 Stages of puberty in boys, 786f in girls, 785f Stages of vision screening, 940 Staging of COPD, 274–275 of HIV/AIDS, 251–252, 252b of lung cancer, 292t Staphylococcus aureus community-acquired methicillin-resistant (CA-MRSA), 232, 592 infection of knee, 618 Startle reflex, 407

Stasis dermatitis, 704 Statins, 102t differences in pharmacokinetics, 482–483 Statistical concepts in prevention, 76–77 Statistical significance of study results interpreting, 115 understanding, 114–115 Status epilepticus, 975 Stavudine, 258t Steepling (of hands), 154f Stem cells, hematopoietic, 877–878 Stenosis aortic, 513–514 carotid artery, 966 mitral, 515–516 spinal, 645–646 subglottic tracheal, 335–336 Stereoscopic tests, 941 Sterilization, 476–477 Sternoclavicular joint injuries, 604 Stevens-Johnson syndrome, 720 Stimulants, for ADHD, 448 Stingers, cervical spine injuries in sports, 584–585 Stomach and duodenal disorders dyspepsia, 848 gastroparesis, 855 GERD, 851–852 peptic ulcer disease, 848–851 upper GI bleeding, 852–855 Strabismus in adults, 949 in children, 941–943 Straight-leg raising test, 638f Strains cervical spine, 634 sports injuries, 584 muscle, in athletes, 595 Strawberry hemangioma, 696f Street names for drugs, 1125t Streptococcal testing, 201–202 Streptokinase, 507t Stress and coping model, 27–28 Stress echocardiography, 501 Stress fractures, 597 Stress incontinence, 48–49, 916 Stressors, 27 normal equilibrium state and, 1025–1026 Stress reduction, as healthy lifestyle factor, 105–106 Stress test ECG, 267 to evaluate syndesmosis, 626 exercise treadmill, 499–500 Stridor, 334–336 Stroke (cerebrovascular accident) acute intervention, 967–968 in diabetes, 753 first-line antiplatelet agents, 965 management of acute stroke, 968–970 pharmacologic therapy, 968 risk factors, 966–967 smoking, 1111–1112 vertebrobasilar, 986 Structured reviews, in HRT, 113 ST-segment elevation MI (STEMI), 505–508 Stye, 933 Subacute cutaneous SLE, 679, 721

Subarachnoid hemorrhage, smoking as risk factor, 1112 Subclinical thyroid disease, 772–773 Subconjunctival hemorrhage, 934 Subcutaneous route, for opioids or antiemetics, 67 Subcuticular sutures, 561 Subglottic tracheal stenosis, 335–336 Subjective global assessment, 836f Substance abuse, 1028t–1029t preventive services, 84–86 Substance use disorder behavioral therapies for, 1131–1132 intoxication and withdrawal, 1129–1130 laboratory testing, 1127 medical management, 1130–1131 pharmacology, 1128–1129 primary care of patients, 1132–1133 screening, 1125–1127 special populations, 1133 terminology, 1124–1125 Subungual hematoma, evacuation of, 566 Sucking reflex, 407 Sudden cardiac death, in athletes, 581–582 Sudden death, sickle cell trait and, 594 Sudden loss of vision, 952t Sudden sensorineural hearing loss, 302 Suicidal ideation, antidepressants and, 1075–1076 Suicide screening, 1068–1069 Sulcus sign evaluation, 609f Sulfasalazine, 662–663 Sulfonamides, exposure in pregnancy, 369t Sulfonylureas, 739–740 Sulfur, nutritional summary, 820t–824t Supplementation dietary. See Dietary supplements insulins, 741 nutritional enteral, 838 parenteral, 838 testosterone, 1007 Support groups, 1050 Supraventricular tachycardia, 542–543 Surface action potential, 534 Surgery for incontinence, 52 for obesity, 815–817 for pediatric cataracts, 946 refractive, 947 as therapy for type 2 diabetes, 744 Sutures placement of, 560–561 types of, 553 Swallowing disorders, 332–333 Sweeteners, 834 Swelling, leg, 524t Symptomatic conditions of GERD, suggesting complicated disease, 853b of HIV/AIDS, 251 Symptom management in multiple sclerosis, 999 Symptom management in terminal illness, 59–67 anxiety and depression, 65 constipation, 66–67 dyspnea, 65–66

1165

Index Symptom management in terminal illness (Continued) hiccup, 67 nausea and vomiting, 67 pain control, 60–65 subcutaneous route, 67 Symptom-oriented treatment, of crisis, 1031–1032 Symptomothermal method of contraception, 473 Syncope, 544 Syndesmosis ankle sprains, 626–627 Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), 765–766 Synovial fluid analysis, 652 for gout, 668 Syphilis, 920–921 latent, 221 in pregnancy, 369–370 primary and secondary, 221 screening, 219t testing, 202 Syrup, morphine, 61t Systemic disorders arthritis of, 654–655 in children, 422b rheumatic fever, 677–678 sclerosis, 684–685 skin signs of dermatomyositis, 722 lupus erythematosus, 720–722 sarcoidosis, 722–723 viral infections, 212–214 Systemic lupus erythematosus (SLE), 182 in childhood, 687–688 clinical features, 678–680 laboratory abnormalities, 680 lung manifestations of, 297 treatment, 680–681 Systems approach, 27 Systems change, preventive health care and, 94–95

T Tablets morphine, 61t vaginal, for incontinence, 51t Tachyarrhythmias, in athletes, 580–581 Tachycardia FHR, 391 junctional, 539 narrow-complex, 543 sinus, 538 supraventricular, 542–543 ventricular, 548f Tachypnea in neonate, 412 transient, in neonate, 414–415 Tachysystole, 392–393 Tadalafil, 1006t Tai chi, 143t Talwin. See Pentazocine Tamsulosin, 51t Tapering, in drug withdrawal, 1130 Tarsal tunnel syndrome, 991–992

1166

Tears meniscus, 622f rotator cuff, 607 Technology in interview process, 170 role of computers in patient education, 164–165 Teeth, sports trauma to, 588–590 Telephone quit lines, for smoking cessation, 1121 Temperament, 431, 433t Temperature, of neonate, 412 Temporal arteritis, 954–955 Temporal classification, of peripheral neuropathies, 987 Tendinopathy, 595–596 Achilles, 628 elbow, 610–611 Tendon injuries in sports histopathology, 595 mechanism of injury, 594–595 tendinopathy, 595–596 Tenecteplase, 507t Tenofovir, 258t Tenosynovitis DeQuervain’s, 613–614 digital flexor, 614 Tension-type headaches, 964 Teratogenic agents, 403b Teratology counseling, 362b Terazosin, 51t Terbutaline, for preterm labor, 378 Terminal illness. See also Dying patient: care of importance of hope, 59 and prognosticating, 57 symptom management, 59–67 and where to die, 68 Tertiary adrenal insufficiency, 779–780 Tertiary prevention services, 74 Tertiary syphilis, 221t Testicular cancer, 926–927 Testicular disorders abnormal puberty, 785–787 delayed puberty, 787–789 gynecomastia, 790 infertility, 790 male hypogonadism, 789 normal sexual development, 784–785 torsion, 911–912 undescended testis, 912 varicoceles, 912 Testosterone replacement, 761 Testosterone supplementation, 1007 Tetracyclines, exposure in pregnancy, 369t Thalassemia, 194t, 884–885 Thelarche, isolated, 786 Theory of reasoned action, 94t Therapeutic communities, for substance use disorders, 1132 Therapeutic lifestyle change, 481t, 482 Therapeutic regimens, CAM, 134t, 136f Thiazide diuretics, effect on lipid values, 195t Thiazolidinediones, 741 Third-degree AV block, 540 Thirdhand smoke, 1115 Third stage of labor, 385–386 Thoracentesis, diagnostic, 298

Thoracolumbar spine anatomy, 636 diagnostic testing, 637 low back pain, 638–641 lumbar disk syndromes, 641–644 physical examination, 636–637 scoliosis, 646 spinal stenosis, 645–646 vertebral compression fractures, 644–645 Thoughts associated with trauma, 1024b irrational, 1040–1048 Thrombocytopenia, 188, 190t, 892–895 Thrombocytosis, 188, 895 Thromboembolic stroke, 967b Thrombolytics, in treatment of acute MI, 507t Thrombosed external hemorrhoids, 567–568 Thrombosis cavernous sinus, 325t in SLE, 680 Thrombotic thrombocytopenic purpura, 894–895 Thrush, 708f Thyroglossal duct cysts, 339 Thyroid disorders anatomic diseases goiter, 773 malignancy, 774 nodules and cysts, 773–774 drugs affecting thyroid function and testing, 775 hyperthyroidism, 769–770 hypothyroidism, 771–772 laboratory testing, 768–769 long-term follow-up of, 774 masses, 341–342 in pregnancy, 775–776 screening for, 776–777 sick euthyroid syndrome, 774–775 subclinical thyroid disease, 772–773 thyroiditis, 772 thyroid orbitopathy, 950 thyrotoxicosis, 770–771 Thyroid gland anatomy and physiology, 767–768 laboratory test, 202–203 Thyroid hormone adaptation syndrome, 774–775 Thyroid hormones, circulating, 767–768 Thyroiditis, 342, 772 Thyroid-stimulating hormone (TSH), 202–203, 768t Thyroid storm, 771 Thyrotoxicosis, 770–771 Thyrotropin. See Thyroid-stimulating hormone (TSH) Thyroxine (T4), 202–203, 767 nodules produced by, 770 Tibial neuropathy, 991–992 Tick-borne infections babesiosis, 230 Colorado tick fever, 231 ehrlichiosis, 228–230 Lyme disease, 230 prevention, 231 Rocky Mountain spotted fever, 228 tularemia, 230–231 Ticlopidine, in elderly, 46t

Index Time demands, and effective communication, 169–170 Timed voiding, 50 Timeline, crisis, 1030–1031 Time–volume spirometry, 264f Tincture, herbal, 1143t Tinea capitis, 710–711, 711f Tinea corporis, 708, 709f Tinea cruris, 710 Tinea pedis, 708–710 vesicular, 691f Tinea versicolor, 711–713, 712f Tinnitus, 308–309 Tipranavir, 258t Tip sutures, 561 Tissue adhesive, 559–560 Tissue plasminogen activator (t-PA), 967 Tobacco-specific nitrosamines, 1115 Tobacco use cancer caused by, 1107f neonatal exposure, 419 preventive services, 84 smokeless tobacco, 1114 α-Tocopherol, nutritional summary, 820t–824t Toddlers eating skills summary, 829f nutrition, 428–430 sleep refusal, 444 Tolerable upper intake levels (TULs), 841 Tolterodine, 51t Tonic neck reflex, 407 Tonsillitis, 330–332 Topical anesthesia, 553–554 Topical corticosteroids, prescribing, 692 Topiramate, 1101 Torsades de pointes, 541 Torsion, testicular, 911–912 Torticollis, 634 Total body sodium (Na), 200t Total iron-binding capacity (TIBC), 193 Total parenteral nutrition (TPN), 67 Total protein, laboratory test, 198–199 Touch, and establishing rapport, 150 Toxic epidermal necrolysis, 720 Toxic neuropathies, 993 Toxoplasma gondii encephalitis, 259t Toxoplasmosis, in pregnancy, 369 Traditional Chinese medicine (TCM), 142t Transcendental meditation, 106 Transcranial magnetic stimulation, 1076 Transcutaneous pulse oximetry, 266 Transdisciplinary health team, 20–21, 22t Transesophageal echocardiography (TEE), 516 Transferrin and iron studies, 193 laboratory test, 827 Transgender health care, 1009 Transient ischemic attack (TIA) in carotid artery disease, 956–957 vertebrobasilar, 986 Transient tachypnea, of newborn, 414–415 Transitioning, of acutely ill patient with diabetic ketoacidosis, 746–747 Transitions, in family life cycle, 30 Transthyretin (TTY), 827

Trauma birth, 416–417 common symptoms associated with, 1024b head and neck, 305 laryngeal, 336 nasal, 329–330 ocular, 936–939 possibly causing delirium, 1080b psychiatric disorders related to, 1028t–1029t sports dental, 589 eye, 589–590 facial, 589 treatments for, 1035 tympanic membrane perforations, 315 Traumatic cataract, 946 Traumatic hyphema, 938–939 Traveler’s diarrhea, 246 Trazodone, 1071t Tremor, with alcohol withdrawal, 1096t–1097t Treponemal antibody tests, 202 Treponema pallidum enzyme immunoassay, 202 Trichomonads, in urine, 902 Trichomonas vaginalis, 223–224 Trichomoniasis, 462–463 Tricuspid valve disease, 518 Tricyclic antidepressants, 1069–1070, 1071t, 1074 dosing data, 66t effect on therapy in anaphylaxis, 357t for migraine, 964t Trigeminal nerve (CN V), 960 Trigeminal neuralgia, 965, 994 Triglycerides, 481–482, 484 Triiodothyronine (T3), 202–203, 767 Trimethobenzamide, in elderly, 46t Trimethoprim-sulfamethoxazole, 233t Triopathy, 749–750 Trisomy18, second trimester screen results, 368t Trochlear nerve (CN IV), 960 Trospium, 51t Tubal ligation, 476 Tube feeding, 67 formulas, 838 Tuberculin positivity, 218b Tuberculosis (TB) diagnosis, 216 differential diagnosis, 274b epidemiology, 215, 282 presentation, 215 screening in children, 427 treatment, 216–218, 283–284 Tuberculous cervical lymphadenitis, 340 Tubulointerstitial disease, 909b Tularemia, 230–231 Tumor necrosis factor (TNF) inhibitor, for rheumatoid arthritis, 664t–665t Tumors carotid body, 340 of ear, 306 lymphoid, 898 pituitary, 757 sinonasal, 329 of thyroid gland, 342 Turbinates, hypertrophied, 322

Twelve-step facilitation, for substance use disorders, 1132 Tympanic membrane rupture, 589 traumatic perforations, 315 Type 1 diabetes mellitus characteristics, 734t medical nutrition therapy, 834 pregnancy and, 748 subacute presentation, 743 symptoms, 735–736 Type 2 diabetes mellitus, 88–89 characteristics, 734t complication of obesity, 808–809 dietary recommendations, 835 fasting plasma glucose level and, 192 healthy lifestyle intervention, 104–105 initiating insulin for, 742–743 pregnancy and, 748 presentation, 735–736 Type II second-degree AV block, 540

U Ulcerative colitis, 864, 866f Ulcerative jejunitis, 873 Ulcers corneal, 935–936 diabetic, 234–235 genital, 219 peptic ulcer disease, 848–851 pressure, in elderly patients, 42–45 Ulnar neuropathy, 990–991 Ultrasound Doppler, for PVD, 527 in evaluation of urinary tract disease, 903 Uncomplicated cystitis, 921 Uninsured persons, 11 Unipolar depression, vs. bipolar depression, 1064–1065 United States, CAM use in 1990s, 133–134 21st century, 134–135 Upper extremity examination, for rheumatoid arthritis, 660 Upper GI bleeding, 852–855 Urease breath tests, 192 Urecholine. See Bethanechol Uremic neuropathy, 993 Urethritis, 222–224 nongonococcal, 223, 920 Urge incontinence, 48 Uric acid, laboratory test, 203 Urinalysis, 50 dipstick, 900–901 specimen preparation, 900 Urinary creatinine, 827 Urinary frequency, 904 Urinary incontinence in elderly patients behavioral interventions, 50 evaluation, 49–50 gender differences, 47 pharmacologic therapies, 51–52 surgical treatment, 52 types of, 48–49 Urinary tract anatomic disorders, 909–912 common concerns, 903–908

1167

Index Urinary tract (Continued) functional disorders, 912–918 imaging studies, 903 infectious disorders, 918–923 laboratory tests, 900–903 neoplastic disorders, 923–927 physical examination, 899–900 Urinary tract infections (UTIs), 226 asymptomatic bacteriuria, 921 catheter-associated, 227 in children, 227, 922–923 complicated infection, 921–922 in pregnancy, 226–227 recurrent, 227, 922 uncomplicated cystitis, 921 Urine, delayed passage in newborn, 413 Urine drug screens, 203–204 Urine free cortisol (UFC), 780 Urobilinogen, 901 Urologic causes, of chronic pelvic pain, 465b Urothelial cells, 902 UroXatral. See Alfuzosin Urticaria, 719 U.S. Preventive Services Task Force (USPSTF) and evidence-based prevention, 74–75 recommendations, 96b–99b for abdominal aortic aneurysm, 83 for adult women, 456t for alcohol abuse, 85 for breast cancer, 80 for cervical cancer, 79 for CHD, 84 for chlamydial infection, 86–87 for colorectal cancer, 78 for depression, 85–86 for diabetes mellitus type2, 89 evidence-based summary, 96b–99b for gonorrheal infection, 87 for healthy diet counseling, 90 for HIV, 88 for hyperlipidemia, 82–83 for osteoporosis, 89 for patient education and counseling, 162t for physical activity counseling, 90 for prostate cancer, 81 Uterine aspiration, 573 Uterine fibroids, 459 Uterine inversion, 401 Uveitis, 951

V Vaccines administration, 438 and HIV-infected children, 440 indications and contraindications for, 437–438 influenza for patients with COPD, 277 seasonal, 281b zoster, 214 Vacuum constriction devices, 1007 Vacuum extraction, 398–399 Vaginal bleeding, abnormal, 456–459 Vaginal contraceptive ring, 474 Vaginal deliveries, operative, 397

1168

Vaginal discharge bacterial vaginosis, 460–461 candidal vaginitis, 461–462 desquamative inflammatory vaginitis, 463 trichomoniasis, 462–463 Vaginal ring, for incontinence, 51t Vaginismus, 1004 Vaginitis atrophic, 466 candidal, 461–462 various forms of, 463 Vaginosis, bacterial, 460–461 Vagus nerve (CN X), 960 stimulation, 1076 Valacyclovir, for HSV infection, 220t Valerian, 1142t–1147t, 1161t Valgus stress, 622f Valvular heart disease aortic stenosis, 513–514 aortic valve regurgitation, 514–515 endocarditis prevention, 518 mitral regurgitation, 516–517 mitral stenosis, 515–516 mitral valve prolapse, 517–518 pulmonic valve disease, 518 tricuspid valve disease, 518 Vanadium supplements, 1147t–1154t Vancomycin, 233t for bacterial meningitis, 244t Vardenafil, 1006t Varenicline, 1119b, 1121 Variability of FHR, 390 Varicella, 213–214, 697 vaccine, 439 Vasa previa, 381 Vascular dementia, 1088 Vascular disease coexisting with PVD, 521 dementia, 971 in diabetes, 753 dietary supplements and, 833–834 Goodpasture’s syndrome, 290 preventive services, 81–84 pulmonary embolism, 287–290 pulmonary hypertension, 289–290 Wegener’s granulomatosis, 290 Vascular parkinsonism, 995 Vasculitic syndromes giant cell arteritis, 683 inflammatory myopathies, 683–684 polymyalgia rheumatica, 683 skip lesions, 682 systemic sclerosis, 684–685 Vasectomy, 476–477 Vasodilators, for hypertensive emergencies, 491t Vasomotor rhinitis, 323 Vasopressin, 763–764 Vasopressin antagonists, 766 Venereal Disease Research Laboratories (VDRL) test, 202, 220–221 Ventilation–perfusion (V/Q) scan, 266 Ventricular myocytes, 533 Ventricular rhythms, 541 Ventricular tachycardia, 548f in athletes, 581

Verbal communication hand-on-the-doorknob syndrome, 148–149 verbal instruction in patient education, 163 vocabulary, 149 Verbal–nonverbal mismatch, 157 Verruca (warts), 714–715 Vertebral compression fractures, thoracolumbar, 644–645 Vertebral spine, 633f Vertigo, 985t benign paroxysmal positional, 307–308 laboratory testing, 306 labyrinthitis, 308 Ménière’s disease, 307 Very-low-density lipoprotein (VLDL), 480 Vesicare. See Solifenacin Vesicoureteral reflux (VUR), 923 Vesicular tinea pedis, 691f Vestibular neuronitis, 307, 985–986 Vestibular schwannoma, 316 Vestibulocochlear nerve (CN VIII), 960 Viagra. See Sildenafil Vibrio spp., in cellulitis, 231–232 Vibroacoustic stimulation, in antepartum fetal surveillance, 383–384 Vicodin. See Hydrocodone Video laryngeal stroboscopy, 334 Videx. See Didanosine Violence, intimate partner, 1023–1025, 1032–1035 Viracept. See Nelfinavir mesylate Viral exanthems, 697 Viral hepatitis, 856–859 Viral infections AIDS-defining illnesses, 251 conjunctivitis, 934 encephalitis, 244 gastroenteritis, 245–246 pharyngitis, 331 pneumonia, 280 in sports medicine, 591–592 systemic, 212–214 Viral meningitis, 983 Viral skin infections herpes simplex, 713–714 herpes zoster (shingles), 714 molluscum contagiosum, 715–716 verruca (warts), 714–715 Viramune. See Nevirapine Virchow’s node, 897 Viread. See Zalcitabine Virilization, isolated, 788t Virtual colonoscopy, 875 Visceral adipose tissue, 492–493 influences on, 807 Vision loss, sudden, 952t Vision screening in healthy children, 426–427 pediatric, 940 Visual acuity testing, 940–941 Vital signs, of neonate, 407t, 411–412 Vitamin A nutritional summary, 820t–824t supplements, 1147t–1154t Vitamin B1 (thiamine) nutritional summary, 820t–824t supplements, 1147t–1154t

Index Vitamin B2 (riboflavin) nutritional summary, 820t–824t supplements, 1147t–1154t Vitamin B3 (niacin, niacinamide) for dyslipidemia, 485–486 nutritional summary, 820t–824t supplements, 1147t–1154t Vitamin B5 (pantothenic acid) nutritional summary, 820t–824t supplements, 1147t–1154t Vitamin B6 (pyridoxine) nutritional summary, 820t–824t supplements, 1147t–1154t Vitamin B9. See Folic acid Vitamin B12 (cobalamin) deficiency, 186, 883–884 nutritional summary, 820t–824t supplements, 1147t–1154t Vitamin C effect on FOBT, 191 nutritional summary, 820t–824t supplements, 1147t–1154t Vitamin D conversion to active form, 797f laboratory test, 204 nutritional summary, 820t–824t supplements, 830t, 1147t–1154t Vitamin E nutritional summary, 820t–824t supplementation, 833–834 supplements, 1147t–1154t Vitamin K administered to neonate, 405–406 nutritional summary, 820t–824t supplements, 1147t–1154t Vitamin supplementation, 830, 833–834, 1141, 1147t–1154t Vitreous floaters, 951 Vocabulary, and establishing rapport, 149 Vocal cord motion, paradoxical, 353 Vocal cord nodules, 337–338 Vocal cord paralysis, 335–337 Voiding, dysfunctional, 914 Voiding (bladder) diaries, 50 Von Willebrand’s disease, 895 Vulvar lesions, 463–464 Vulvovaginal candidiasis, 461–462 Vyvanse. See Lisdexamfetamine

W Walking, for diabetes mellitus management, 738 Warning symptoms in athletes, 579 Warts, 714–715 genital, 225t Water, nutritional summary, 820t–824t Water balance, impaired, 199–200 Weakness facial, 318–319 muscle, 961 Wegener’s granulomatosis, 290 Weight gain pregnancy outcomes linked to, 828t recommended for pregnant women, 362t Weight loss for diabetes mellitus, 737 for metabolic syndrome, 494–495 for PVD, 529 Well-woman examination, 455–456 Wet bulb globe temperature (WBGT) index, 586 Wheel-and-spoke formulation of crisis, 1031 Wheezing, in asthma, 269–270 Whiplash, 634 White blood cells (WBCs), 888–892 disorders of neutrophils, 889–891 eosinophilia, 891–892 laboratory test, 188 leukocytosis stratified by, 189t monocyte and macrophage disorders, 892 in urine, 901 White House Commission 2002 Report, on CAM, 135, 138t Wilms tumor, 927 Withdrawal alcohol, 1095–1098 nicotine, 1119b opiates, 1129 sedative-hypnotics, 1130 Women’s health, 360–361 abnormal vaginal bleeding in adolescents, 457 in perimenopausal women, 458–459 in postmenopausal women, 459 in reproductive-age women, 457–458 alcohol use disorder, 1101–1102 recommended dietary allowances, 363t sexual dysfunction, 1002–1005 well-woman examination, 455–456

Women’s Health Initiative summary rates from, 114t website, 127f Women’s Health Study, 105, 106t–107t Workflow management, 122 Work-related asthma, 293 Work-related pulmonary cancers, 294 World Health Organization (WHO) criteria for screening test, 74t medical eligibility criteria, 469–470 Worldview of difficult patient, 1050 Wound assessment, of pressure ulcers, 42 Wound healing hypertrophic scars, 558 keloids, 556 nonhealing wounds, 558 stages of, 556 wound dressings, 558 Wound irrigation, 555 Wound management, of bite wounds, 238t–239t Wrinkles, smoking and, 1112 Wrist and hand injuries, 612–616

X Xerostomia, 341

Y Yoga, 141–144, 143t Yohimbe, 1142t–1147t Yohimbine, 1007 Yucca, 1142t–1147t

Z Zalcitabine, 258t Zanamivir, 213t Zerit. See Stavudine Ziagen. See Abacavir Zinc nutritional summary, 820t–824t supplements, 1147t–1154t Z-plasty, 561 Zyloprim. See Allopurinol

1169

Textbook of Family Medicine, 8th Edition

Textbook of Family Medicine

Cancer Medicine, 8th Edition

Kelley's Textbook of Rheumatology, 8th Edition

Textbook of Family Practice

Textbook of Family Practice

Textbook of Natural Medicine

Textbook of Rabbit Medicine

Textbook of Natural Medicine

The Textbook of Pharmaceutical Medicine, Sixth Edition

The Textbook of Pharmaceutical Medicine Fourth edition

Textbook of Cardiovascular Medicine

Textbook of Musculoskeletal Medicine

Oxford Textbook of Medicine

Textbook of Personalized Medicine

Textbook of Rabbit Medicine

Cecil Textbook of Medicine

Family Medicine Obstetrics (Third Edition)

Textbook of Stroke Medicine (Cambridge Medicine)

Textbook of Pediatric Emergency Medicine

Oxford Textbook of Palliative Medicine

Textbook of Pediatric Psychosomatic Medicine

Essentials of Family Medicine (Sloane, Essentials of Family Medicine)

Textbook of Pediatric Emergency Medicine

The Textbook of Pharmaceutical Medicine

Oxford Textbook of Geriatric Medicine

Textbook of Primary Care Medicine

Textbook of Pediatric Emergency Medicine

Kaplan and Sadock's Comprehensive textbook of Psychiatry 8th edition

Concise Oxford Textbook of Medicine

Concise Textbook of Forensic Medicine & Toxicology, 3rd Edition

Textbook of Family Medicine, 8th Edition