GULF WAR and HEALTH

Treatment for
Chronic Multisymptom Illness

Committee on Gulf War and Health:
Treatment for Chronic Multisymptom Illness

Board on the Health of Select Populations

INSTITUTE OF MEDICINE

OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
Washington, D.C.
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GULF WAR and HEALTH Treatment for Chronic Multisymptom Illness Committee on Gulf War and Health: Treatment for Chronic Multisymptom Illness Board on the Health of Select Populations

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THE NATIONAL ACADEMIES PRESS  500 Fifth Street, NW  Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee respon- sible for the report were chosen for their special competences and with regard for ­appropriate balance. This study was supported by Contract VA241-P-2024 between the National Acad- emy of Sciences and the Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the organizations or agencies that provided support for the project. International Standard Book Number-13:  978-0-309-27802-7 International Standard Book Number-10:  0-309-27802-3 Additional copies of this report are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; Internet, http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2013 by the National Academy of Sciences. All rights reserved. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin. Suggested citation: IOM (Institute of Medicine). 2013. Gulf War and Health: ­ reatment for Chronic Multisymptom Illness. Washington, DC: The National T Academies Press.

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“Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe Advising the Nation. Improving Health.

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The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Acad- emy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineer- ing programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is presi- dent of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Insti- tute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sci- ences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The C ­ ouncil is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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COMMITTEE ON GULF WAR AND HEALTH: TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS BERNARD M. ROSOF (Chair), Chairman, Board of Directors, Huntington Hospital, Huntington, NY DIANA D. CARDENAS, Professor and Chair, Department of Rehabilitation Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL FRANK V. deGRUY, Woodward-Chrisholm Professor and Chair, Department of Family Medicine, University of Colorado School of Medicine, Aurora, CO DOUGLAS A. DROSSMAN, Adjunct Professor of Medicine and Psychiatry, Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina School of Medicine, and Drossman Center for the Education and Practice of Biopsychosocial Care, Chapel Hill, NC FRANCESCA C. DWAMENA, Professor and Acting Chair, Department of Medicine, Michigan State University, East Lansing, MI JAVIER I. ESCOBAR, Associate Dean for Global Health, University of Medicine & Dentistry of New Jersey, New Brunswick, NJ WAYNE A. GORDON, Jack Nash Professor and Vice Chair, Department of Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY ISABEL V. HOVERMAN, Physician, Austin Internal Medicine Associates, LLP, Austin, TX WAYNE JONAS, President and CEO, Samueli Institute, Alexandria, VA JOANNA G. KATZMAN, Associate Professor, Department of Neurosurgery, University of New Mexico School of Medicine, Albuquerque, NM ELAINE L. LARSON, Associate Dean for Research, Columbia University School of Nursing, New York, NY STEPHEN RAY MITCHELL, Dean of Medical Education, Georgetown University School of Medicine, Washington, DC KAREN A. ROBINSON, Assistant Professor, Departments of Medicine, Epidemiology, and Health Policy and Management, Johns Hopkins University, Baltimore, MD KASISOMAYAJULA VISWANATH, Associate Professor, Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA LORI ZOELLNER, Associate Professor, Department of Psychology, University of Washington, Seattle, WA v

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Staff ABIGAIL MITCHELL, Study Director CARY HAVER, Associate Program Officer JONATHAN SCHMELZER, Senior Program Assistant NORMAN GROSSBLATT, Senior Editor GARY WALKER, Financial Officer JIM BANIHASHEMI, Financial Officer FREDERICK ERDTMANN, Director, Board on the Health of Select Populations vi

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Reviewers This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as pos- sible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the delibera- tive process. We thank the following for their review of the report: Niloofar Afari, University of California, San Diego Melvin S. Blanchard, Washington University School of Medicine Paul W. Brandt-Rauf, University of Illinois at Chicago School of Public Health Sandro Galea, Columbia University Mailman School of Public Health Naomi L. Gerber, George Mason University Thomas V. Holohan, Clinical Evaluation, LLC; formerly Veterans Health Administration David R. Nerenz, Henry Ford Health System Eliseo J. Perez-Stable, University of California, San Francisco Karen S. Quigley, Northeastern University and Edith Nourse Rogers Memorial VA Medical Center Sandra J. W. Smeeding, Veterans Affairs Salt Lake City Health Care System Nancy Fugate Woods, University of Washington School of Nursing vii

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viii REVIEWERS Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of the report was overseen by Lynn R. Goldman, Dean, the George Washington University School of Public Health and Health Services, and Enriqueta C. Bond, President Emeritus, Burroughs Wellcome Fund. Appointed by the National Research Council and the Institute of Medicine, respectively, they were responsible for making certain that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully con- sidered. Responsibility for the final content of the report rests entirely with the authoring committee and the institution.

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Preface The committee was convened to review, evaluate, and summarize the available scientific and medical literature regarding the best treatments for chronic multisymptom illness (CMI) in Gulf War veterans. We accepted that responsibility in recognition of the personal and family sacrifices that all soldiers—both deployed and nondeployed—undertake in times of conflict. About 700,000 military personnel served in the 1991 Gulf War, and as of September 2011, about 2.6 million military personnel had been deployed to the Iraq and Afghanistan wars. There is no script for the stresses that are endured; they are personal and many. The committee was most appreciative of the willingness of many veterans to share their experi- ences and thoughts with us so that we would be better prepared to move forward with our task. We undertook a thorough review of the studies1 ­ already completed by the Institute of Medicine (IOM) on this general topic and then expanded the evidence base by conducting a systematic search of the available scientific and medical literature regarding the best treatments for CMI. The committee evaluated the evidence by using the scientifically rigorous process detailed in this report. As we approached the task at hand, we stood firm on the concerns for patient-centered care and our abilities to communicate our thoughts, conclusions, and recommendations to all interested audiences. 1  IOM (Institute of Medicine). 2001. Gulf War Veterans: Treating Symptoms and Syndromes. Washington, DC: National Academy Press; IOM. 2010. Gulf War and Health, Volume 8: Update of Health Effects of Serving in the Gulf War. Washington, DC: The National Acad- emies Press. ix

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x PREFACE To focus our efforts, we defined CMI as the presence of a spectrum of chronic symptoms experienced for 6 months or longer in at least two of six categories—fatigue, mood and cognition, musculoskeletal, gastrointes- tinal, respiratory, and neurologic—that may overlap with but are not fully captured by known syndromes (such as irritable bowel syndrome, chronic fatigue syndrome, and fibromyalgia) or other diagnoses. Our review of the literature revealed that specific etiologic agents or histopathologic findings often are not associated with such symptoms, and the causes of many of the symptoms ascribed to CMI remain unknown. However, the lack of diagnostic and etiologic clarity does not undermine the legitimacy of the reports of the symptoms. The multiple manifestations of the symptoms make directed treatment more challenging, and clinicians are often frustrated by the difficulties in managing care for people who have CMI. However, for veterans whose function and life satisfaction are limited by their symptoms, it remains no less important. We hope that our recommendations will make a difference in the lives of people who have CMI. It is clear that this condition has adversely affected the health and well-being of a substantial number of our veterans and their families. Anecdotal reports appear regularly in the mass media.2 We encourage the Department of Veterans Affairs (VA) to apply the prin- ciples set forth in this report, including at a minimum adequate resources to ensure early entry into the VA health care system and adherence to the principles of patient-centered and compassionate care, shared decision m ­ aking, and regular clinical follow-up as necessary. Our veterans deserve the very best health care. The committee thanks everyone who presented and participated in discussions during the public meetings, which informed our work and helped us to develop our approach to and thought process regarding the statement of task. The wide variety of viewpoints were expressed during those information sessions provided valuable insight into the complexity of medical treatment for CMI in Gulf War veterans. The time and effort to travel to the public meetings and prepare written materials and statements are greatly appreciated. The committee is particularly appreciative of the many Gulf War vet- erans who spoke and submitted written accounts of their experiences in the gulf and on their return to the United States. They provided valuable understanding of the symptoms and medical conditions of CMI and of medical treatment for it as experienced by the many men and women who served in the Gulf War. The committee also owes a debt of gratitude to the following persons who traveled to and presented valuable information at our public meetings: 2  For example, Kristof, N. D. 2012. War wounds. New York Times, August 10, SR1.

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PREFACE xi Caroline Blaum, University of Michigan Health System; Daniel Clauw, University of Michigan Health System; Jeffery Dusek, Abbott Northwestern ­ Hospital; Charles Engel, Deployment Health Clinical Center; Beatrice Golomb, University of California, San Diego, School of Medicine and San Diego VA Medical Center; Stephen Hunt, VA Puget Sound Health Care Sys- tem; Kenneth Kendler, Virginia Commonwealth University; Kurt Kroenke, Regenstrief Institute; Ronald Poropatich, US Army Medical Research and Materiel Command; and Matt Reinhard, War-Related Illness and Injury Study Center, Washington, DC. The committee thanks Patrick Furey of Consumersphere, a consultant who provided an analysis of the social media discussion surrounding CMI in veterans of the Gulf War. We also thank Michael Peterson and Terry W ­ alters, of the VA Office of Public Health, for providing helpful back- ground information. I would like to thank the committee members for their time commit- ment to this important project, their diligence in reviewing every detail of complex issues, and their sensitivity to the concerns of our veterans. Finally, I thank the IOM staff for their thoroughness, knowledge, research exper- tise, and guidance throughout this journey to try to make a contribution to the understanding of a complex subject. Bernard M. Rosof, Chair Committee on Gulf War and Health: Treatment for Chronic Multisymptom Illness

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Contents ABBREVIATIONS AND ACRONYMS xix SUMMARY 1 1 INTRODUCTION 11 Prior Efforts to Address Chronic Multisymptom Illness in Gulf War Veterans, 11 The Charge to the Committee, 13 The Gulf War Veteran Population, 15 Gulf War Veterans’ Experiences with Diagnosis of and Treatment for Chronic Multisymptom Illness, 16 Organization of This Report, 17 References, 18 2 CHARACTERIZING CHRONIC MULTISYMPTOM ILLNESS 21 Terminology, 21 The Committee’s Working Definition of Chronic Multisymptom Illness, 23 Chronic Multisymptom Illness in Civilian and Veteran Populations, 24 Veteran vs Civilian Populations, 26 Managing vs Curing Chronic Multisymptom Illness, 26 References, 27 xiii

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xiv CONTENTS 3 METHODS 29 Systematic Review of Treatments for Chronic Multisymptom Illness, 30 Treatments for Comorbid Conditions with Shared Symptoms, 32 Additional Sources of Information, 34 Current Research on Chronic Multisymptom Illness, 35 References, 35 4 TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 37 Pharmacologic Interventions, 38 Other Biologic Interventions, 40 Psychotherapies, 41 Mind–Body Approaches, 56 Exercise, 79 Discussion, 79 References, 87 5 REVIEW OF TREATMENTS FOR COMORBID AND RELATED CONDITIONS 93 Fibromyalgia, 94 Chronic Pain, 95 Chronic Fatigue Syndrome, 97 Somatic Symptom Disorders, 100 Sleep Disorders, 101 Functional Gastrointestinal Disorders: Irritable Bowel Syndrome and Functional Dyspepsia, 102 Depression, 106 Anxiety, 108 Posttraumatic Stress Disorder, 109 Traumatic Brain Injury, 111 Substance-Use and Addictive Disorders, 113 Self-Harm, 116 General Therapeutic Approach, 119 References, 123 6 PATIENT-CENTERED CARE OF VETERANS WHO HAVE CHRONIC MULTISYMPTOM ILLNESS 133 Clinician Training, Practice Behaviors, and Chronic Multisymptom Illness, 133 Improving Communication Skills and the Patient–Clinician Relationship, 136 Information and Communication Technologies, Communication Inequalities, and Chronic Multisymptom Illness, 146 References, 149

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CONTENTS xv 7 IMPLEMENTATION AND MODELS OF CARE FOR VETERANS WHO HAVE CHRONIC MULTISYMPTOM ILLNESS 155 Models of Care for Chronic Multisymptom Illness in the Department of Veterans Affairs Health Care System, 156 Gulf War Veterans’ Experience of Care, 161 An Approach to Organizing Services for Care of Veterans Who Have Chronic Multisymptom Illness, 167 Select Models of Care Used by Other Organizations, 173 Disseminating Evidence-Based Guidelines Through the Department of Veterans Affairs System, 173 Clinicians’ Behavior Change: System and Interpersonal Determinants, 175 Summary, 176 References, 177 8 RECOMMENDATIONS 183 Treatments for Chronic Multisymptom Illness, 183 Improving Care of Veterans Who Have Chronic Multisymptom Illness, 186 Dissemination of Information, 188 Improving Data Collection and Quality, 190 Research Recommendations, 190 References, 192 APPENDIXES A Committee Biographic Sketches 195 B Possible Factors Underlying Chronic Multisymptom Illness 203 C Examples of Effective and Ineffective Patient–Clinician Discussions 207 INDEX 211

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Boxes, Figures, and Tables BOXES 1-1 The Committee’s Charge, 14 2-1 Symptoms and Related Functional Impairment Reported by Veterans of Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn, 25 5-1 Definitions of Chronic Fatigue Syndrome, 98 5-2 Rome III Diagnostic Criteria for Irritable Bowel Syndrome, 103 5-3 Rome III Diagnostic Criteria for Functional Dyspepsia, 104 5-4 Assessing for Suicidal Ideation, 117 6-1 Additional Resources for Clinicians, 145 7-1 Department of Veterans Affairs (VA) Health Care Enrollment Priority Groups, 164 C-1 Example of an Ineffective Patient–Clinician Discussion, 208 C-2 Example of an Effective Patient–Clinician Discussion, 209 xvii

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xviii BOXES, FIGURES, AND TABLES FIGURES 3-1 Summary of search and review process, 33 7-1 Institute for Healthcare Improvement Plan Do Study Act model, 171 B-1 Putative mechanism by which the body perceives symptoms, 204 TABLES 3-1 AHRQ’s Strength-of-Evidence Grades and Definition, 34 4-1 Strength of Evidence on Pharmacologic Interventions, 41 4-2 Pharmacologic Interventions, 42 4-3 Strength of Evidence on Other Biologic Interventions, 48 4-4 Other Biologic Interventions, 48 4-5 Strength of Evidence on Psychotherapies, 55 4-6 Psychotherapies, 56 4-7 Strength of Evidence on Biofeedback Interventions, 73 4-8 Biofeedback Interventions, 74 4-9 Strength of Evidence on Cognitive Rehabilitation Therapies, 76 4-10 Cognitive Rehabilitation Therapy, 76 4-11 Strength of Evidence on Complementary and Alternative Therapies, 78 4-12 Complementary and Alternative Therapies, 80 4-13 Strength of Evidence on Exercise Interventions, 84 4-14 Exercise Interventions, 84 5-1 Best-Practice Guidelines and Recommendations for Treatment for Nightmare Disorders and Chronic Insomnia, 102 5-2 Stratification of Severity of Traumatic Brain Injury, 112 5-3 Summary of Treatments Recommended in Guidelines or Found to Be Effective in Systematic Reviews for Conditions Comorbid with and Related to Chronic Multisymptom Illness, 120 6-1 Behaviors That Influence Accurate Data Collection, 142 6-2 Characteristics of Users of Social Media, 148

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Abbreviations and Acronyms AACH American Academy on Communication in Healthcare ACP American College of Physicians AHRQ Agency for Healthcare Research and Quality ALS amyotrophic lateral sclerosis AMSTAR Assessment of Multiple Systematic Reviews AOC alteration of consciousness APA American Psychiatric Association BMI body mass index CACTUS Classical Acupuncture Treatment for People with Unexplained Symptoms CAM complementary and alternative medicine CBOC community-based outpatient clinic CBT cognitive behavioral therapy CDC Centers for Disease Control and Prevention CFS chronic fatigue syndrome CI confidence interval CINAHL Cumulative Index to Nursing and Allied Health Literature CMI chronic multisymptom illness CPAP continuous positive airway pressure CPG clinical practice guideline CQI continuous quality improvement CRT cognitive rehabilitation therapy xix

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xx ABBREVIATIONS AND ACRONYMS DARE Database of Abstracts of Reviews of Effects DNA deoxyribonucleic acid DOD Department of Defense DSM Diagnostic and Statistical Manual of Mental Disorders DU depleted uranium EBI evidence-based information ECHO Extension for Community Healthcare Outcomes ECT electroconvulsive therapy EMC enhanced medical care EMDR eye-movement desensitization and reprocessing FD functional dyspepsia FDA Food and Drug Administration FGID functional gastrointestinal disorder FPOW former prisoner of war FSS functional somatic syndrome FY fiscal year GET graded exercise therapy GI gastrointestinal GMT geographically adjusted income threshold GWI Gulf War illness GWV Gulf War–deployed veterans GWVI Gulf War veterans illness IBS irritable bowel syndrome ICT information and communication technology IHI Institute for Health Improvement IOM Institute of Medicine LOC loss of consciousness ME myalgic encephalomyelitis MI motivational interviewing mTBI mild traumatic brain injury MUPS medically unexplained physical symptoms MUS medically unexplained symptoms NHS National Health Service (UK) NICE National Institute for Health and Clinical Excellence (UK) NSAID nonsteroidal anti-inflammatory drug

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ABBREVIATIONS AND ACRONYMS xxi OEF Operation Enduring Freedom OIF Operation Iraqi Freedom OND Operation New Dawn OR odds ratio PC primary care PCMH patient-centered medical home PCS postconcussive symptom PD-PACT postdeployment patient-aligned care team PIT psychodynamic interpersonal therapy PTA posttraumatic amnesia PTSD posttraumatic stress disorder RAC VA Research Advisory Committee on Gulf War Veterans’ Illnesses RCT randomized controlled trial REAC-BS radioelectric asymmetric brain stimulation REM rapid eye movement RoB risk of bias SCAN Specialty Care Access Network SHAD Shipboard Hazard and Defense SIGLE System for Information on Grey Literature in Europe SNRI serotonin norepinephrine reuptake inhibitor SSD somatic symptom disorder SSRI selective serotonin reuptake inhibitor TBI traumatic brain injury TENS transcutaneous electric nerve stimulation UK United Kingdom VA Department of Veterans Affairs VAMC VA medical center VA-OIG VA Office of the Inspector General VBA Veterans Benefits Administration VHA Veterans Health Administration VISN Veterans Integrated Service Network WGO World Gastroenterology Organisation WRIISC War-Related Illness and Injury Study Center

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