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Health Consequences of Service During the Persian Gulf War: Recommendations for Research and Information Systems Committee to Review the Health Consequences of Service During the Persian Gulf War Medical Follow-up Agency Institute of Medicine NATIONAL ACADEMY PRESS Washington, D.C. 1996

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NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, D.C. 20418 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 responsible for the report were chosen for their special competencies and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. Support for this study was provided equally by the Department of Veterans Affairs and the Department of Defense (Contract Not V101~93)P-1417~. International Standard Book No. 0-309-05536-9 Additional copies of the report are available for sale from: National Academy Press Box 285 2101 Constitution Avenue, N.W. Washington, D.C. 20055 Call 800-624-6242 or 202-334-3313 (in the Washington metropolitan area) Copyright 1996 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 image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin.

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COMMITTEE TO REVIEW THE HEALTH CONSEQUENCES OF SERVICE DURING THE PERSIAN GULF WAR JOHN C. BAILAR III,* Committee Chair, Professor and Chair, Department of Health Studies, University of Chicago, Chicago, Illinois CHRISTOPHER C. GREEN, Executive Director, Research and Development, General Motors Corporation, Warren, Michigan RICHARD B. HORNICK, Vice-President of Medical Education, Orlando Regional Healthcare System, Medical Education Administration, Orlando, Florida KARL T. KELSEY, Associate Professor of Occupational Medicine and Radiobiology, Harvard School of Public Health, Boston, Massachusetts WAYNE M. LEDNAR, Corporate Medical Director, Eastman Kodak Company, Rochester, New York THOMAS A. LOUIS, Professor and Head, Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, Minnesota GARY M. MARSH, Professor, Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania DAVID P. RALL,* Institute of Medicine Foreign Secretary, Washington, D.C., Director, Emeritus, National Institute of Environmental Health Sciences, National Institute of Health, Bethesda, Maryland PHILIP K. RUSSELL, Professor, Department of International Health, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland DAVID A. SAVITZ, Professor and Chairman, Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, North Carolina G. MARIE SWANSON, Director, Cancer Center, and Professor, Department of Family Practice and Medicine, Michigan State University, East Lansing, Michigan GUTHRIE L. TURNER, Jr., Chief Medical Consultant, Department of Social and Health Services, Division of Disability Determination Services, Washington State, Olympia, Washington MARK J. UTELL, Professor, Department of Medicine and Environmental Medicine and Director, Pulmonary/Critical Care and Occupational Medicine Divisions, University of Rochester School of Medicine, Rochester, New York JAMES H. WARE, Dean for Academic Affairs, Harvard School of Public Health, Boston, Massachusetts DAVID H. WEGMAN, Professor and Chair, DeparUnent of Work Environment, University of Massachusetts, Lowell, Massachusetts *Member, Institute of Medicine . . . zi!

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LOUIS JOLYON WEST, Professor, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, School of Medicine, Neuropsychiatric Institute, Los Angeles, California ELIZABETH A. WILLIAMS, Associate Professor, DeparDnent of Internal Medicine, James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee NANCY FUGATE WOODS,* Director, Center for Women's Health Research and Professor, Family and Child Nursing, University of Washington, Seattle, Washington Study Staff DIANE J. MUNDT, Study Director AMANDA H. MURRAY, Research Associate CARLISS PARKER-SMITH, Project Assistant IV

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Preface The Committee to Review the Health Consequences of Service During the Persian Gulf War was charged to assess actions taken by the secretaries of the Department of Defense (DoD) and the Department of Veterans Affairs (DVA) to collect and maintain data on the health of Persian Gulf veterans, to make recommendations to improve the collection and maintenance of such data, and to determine whether there is a sound scientific basis for an epidemiologic study of the health consequences of service and, if so, to recommend the types of studies that should be undertaken. The committee presents 14 findings and 16 recommendations that are intended to improve the nation's understanding of the health consequences of military service in the Persian Gulf, to ameliorate or prevent future health consequences to troops deployed there or in other conflicts, and to improve and accelerate the collection of the information necessary for studying potential problems in the future. As we publish this report, it will have been about 6 years since approximately 697,000 Americans were deployed to the Persian Gulf, while a nation watched the war unfold on the various news networks. Many questions remain about the health of Persian Gulf veterans and the possible causes of the medical symptoms that many veterans have reported. Some persons believe that a new "Gulf War Syndrome" has appeared and that the symptoms and illnesses that are unexplained are in fact a new disease. v

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Vl PREFACE In January 1995, this committee published a first report, Health Consequences of Service During the Persian Gulf War: Initial Findings and Recommendations for Immediate Action (Washington, D.C.: National Academy Press), that was critical of the initial actions taken by the DoD and DVA to address these questions, but we are encouraged that these and other organizations have improved their approach to dealing with the medical and social issues in a more organized, coordinated, sympathetic, and effective manner. However, there is still much to do and we trust that the additional recommendations in this report will contribute to further improvements. The questions of whether a Gulf War veteran is ill and whether that illness was caused by Persian Gulf service are separate and distinct. Our charge and this report address ways to approach the latter question. The former question, although not in the committee's charge, was ever present in its deliberations. The committee was provided with ample evidence that there are veterans who are sick, and we are concerned that they all be provided with proper diagnosis and care. Those of us who were not in the Gulf can only imagine what it was like for the thousands of men and women who were uprooted from families, jobs, and daily existence; to be suddenly transported to a harsh climate; to be injected with vaccines not previously used in the active military; to wait many months for "action" to occur; to wonder whether the war would involve chemical and biological warfare; to witness a brief but intense battle with many enemy casualties; and then, just as suddenly, to return to their earlier routine of daily living in the United States. ~ ~~ ~ ~~ Men and women served side by side under conditions that increased the stresses connected with being in these grim surroundings. How all these Gulf experiences relate to the health of veterans is a complex and challenging question. Although determination of whether a new disease or new syndrome has appeared was not in the committee's charge, we frequently discussed this issue because it helped to enlighten and focus our discussions about the matters we were asked to address. There is a long history in medicine of controversy over the existence of conditions that had not been seen earlier or had not been recognized as separate disease entities. Some of these claimed conditions have faded away, whereas others have become established and generally accepted. Recent examples of the latter are AIDS, Legionnaires' disease, and toxic shock syndrome. For a disease designation to be accepted as valid, criteria need to be set for the diagnosis of that disease so that there will be consistency in reporting. At this time, although studies of Gulf War veterans suggest that these veterans suffer from a variety of recognized diseases, such studies do not establish the existence of a new disease. It is possible that additional findings from research in progress will suggest a new medical entity. Further efforts to identify a Gulf War Syndrome, if it exists, will require substantial new evidence from any

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PREFACE . . V11 research undertaken, but again this issue is separate from whether these ill people need medical care. Signs and symptoms without a diagnosis or apparent cause are found in every medical practice; clinical medicine is neither perfect nor all-knowing. Although physicians may fail to provide a medical reason for some of these signs and symptoms, the illnesses and related disability have to be addressed as well as possible, independent of efforts to understand causes. All of us in the health care and public health fields are committed to using the scientific study methods available to us in an attempt to understand and better explain what is presently unknown. Only in this way can we make progress in defining, preventing, and treating disease. Observations, information, and reports by individual veterans provide insight into what it was like to serve in the Gulf, and studies that are now being designed should continue to seek out and consider input from those who were there. Unstructured reports can direct attention to problems that need study, but only rarely can they provide definitive evidence about the appearance of a new medical problem. That is the case with the Gulf War Syndrome. The numerous moving personal stories about illness in returned veterans have rightly generated concern, followed by preliminary research studies. Investigators still will need to use appropriate study designs and methods to obtain the best possible information, conduct equally appropriate analyses, and systematically evaluate the evidence. Knowledge gained in this way will not only benefit the Persian Gulf veterans, but will also help guide DoD and DVA to identify preventive actions that could lessen the likelihood of adverse health outcomes of future deployments. There may also be important extensions to the diagnosis and treatment of exposures and stresses in the civilian population. Our report is intended to be an evidence-based assessment, so conclusions are inevitably shaped by the evidence that was available at the time the report was written. A substantial research effort is under way, and understanding of the health effects of the Persian Gulf War will evolve as new findings emerge. At the time this report was sent for external review in June 1996, the committee learned that a bunker destroyed in March 1991 may have contained a chemical warfare agent and that troops located 3 or more miles away might have been exposed. DoD officials appearing at a press conference indicated that investigation of this and other incidents is ongoing. Details have since been added (Transcript from President's Advisory Committee on Persian Gulf Veterans' Illnesses, Chicago, Illinois, July 8-9, 1996, and Denver, Colorado, August 6, 1996; Persian Gulf Veterans' Illnesses Investigative Team posting on the Internet, August 6, 1996~. The late reporting of this incident and the press conference statement that the investigation of records from the war is still not finished continue to raise questions about the completeness of exposure information provided by DoD to date. We encourage disclosure of all

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. . . V111 PREFACE information that may inform the public understanding about the health effects of Persian Gulf service. As a committee, we are concerned about the health effects of military service, and we are hopeful that DoD and DVA will consider our recommendations to improve the body of information and preventive interventions for the health of Persian Gulf War and future veterans. Many persons helped the committee in the preparation of this report. First, we have been blessed with an unusually strong staff. Dr. Diane Mundt, as study director, brought to this task a great store of knowledge about epidemiology, biostatistics, military health records, chemical hazards in the field, and related matters, but even more important were her constant oversight of each part of our work and of the role of each committee member; her gently persuasive urging to complete this task, improve on that one, and start a third; and her remarkably comprehensive knowledge about other efforts to understand and improve the health of Gulf War veterans. While the committee wrote the text and takes full responsibility for it, Dr. Mundt's comprehensive attention to improving how we presented our work has made it a far stronger document. Appendixes E, F. and G are among her many contributions. Ms. Amanda Hull Murray was tireless in supporting Dr. Mundt and the committee, with special responsibilities for the critical tasks of learning about and obtaining countless documents (only a fraction could be cited here), coordinating the many presentations to the committee, and aiding veterans and others who had information of potential value to us. Ms. Carliss Parker-Smith supported the work of the office and arranged the details of our 14 committee meetings no mean task with 18 sometimes fractious committee members and countless other persons simultaneously clamoring for attention to their questions and contributions. We also thank Ms. Laura Baird and Ms. Susan Fourt for library assistance; Mr. Michael Edington, Ms. Janet Ross, and Ms. Florence Poillon for editorial assistance; many government and nongovernment agencies and organizations for information provided; and countless individuals, including the Persian Gulf veterans who provided both input and insight. Appendixes C and D give some specifics about the persons and organizations who were helpful in this respect. John C. Bailar III, Chair

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Contents EXECUTIVE SUMMARY Recommendations, 10 1. INTRODUCTION............... An Emerging Problem, 15 Panels and Committees, 17 Conclusions, 20 Charge to the Committee, 21 Research and Data Issues, 22 The POW as the Less-than-Ideal Setting for Research, 23 Where Do We Go from Here?, 25 2. CHARGE TO THE COMMITTEE: ITS FINDINGS AND RECOMMENDATIONS ...... Overview, 26 The Committee's Charge, 26 Charge 1, 26 Charge 2, 27 Charge 3, 27 Findings and Recommendations, 28 14 IX 26

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x 3. ENVIRONMENT AND EXPOSURES Overview, 36 Natural Environment, 39 Man-Made Environment, 42 Pesticides, 42 Fuels and Decontamination Solution, 43 Oil Well Fires and Spills, 44 Occupational Exposures, 47 Diet, 48 Vaccines and Prophylactic Treatment, 49 Pyridostigmine Bromide, 52 Interactions of Exposures, 53 Depleted Uranium, 55 Psychosocial Exposures, 57 Stressors Associated with Deployment, 59 Anticipation of Combat, 59 Combat Exposure, 60 Aftermath and Long-Term Adjustment, 61 Gender Differences in Exposure to Stress, 63 DVA Environmental Hazards Research Centers, 64 4. HEALTH OUTCOMES ............................................................................... Overview, 67 Mortality Studies, 72 Hospitalization Studies, 74 Diagnosed Diseases in PG Veterans, 78 DVA Persian Gulf Health Registry, 79 DoD Comprehensive Clinical Evaluation Program, 81 Predictors of Enrollment in the Persian Gulf Health Registry, 83 Studies of Self-Reported Symptoms, 83 Outbreak Studies, 83 Surveys, 89 Adverse Reproductive Outcome Studies, 93 Pathways for Environmental Influences on Reproduction, 93 Definition of Outcomes, 94 Frequency of Events in the General Population, 96 Confounding, 96 Reproductive Outcome Studies in PG Populations, 97 Mental Health Studies, 101 Issues in Studies of Mental Health, 101 Mental Health Problems and Military Experience, 102 Mental Health: Comparison of Deployed and Nondeployed Troops, 102 CONTENTS ...... 36 .67

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CONTENTS Factors Associated with Mental Health Problems: Combat and Other Stressors, 105 Factors Increasing Vulnerability to PTSD and Other Psychiatric Disorders, 105 Factors Enhancing Resilience or Buffering Effects of Stress on Mental Health, 106 Long-Term Mental Health Outcomes, 107 Physical Symptoms and Exposure to Stressors, 107 Discussion of Mental Health Issues, 109 Women, s Health Studies, 111 Health Effects of Combat Service for Women, 111 Gender Differences in Health, 113 Health Issues Related to Men and Women Serving Together in Combat Situations, 116 5. SOME HYPOTHESES REGARDING ILLNESSES IN PERSIAN GULF WAR VETERANS............... Overview, 117 Chronic Fatigue Syndrome, 118 Multiple Chemical Sensitivity, 119 Oxidative Phosphorylation Disorder, 120 Dental Amalgams, 120 Bacterial Illness, 121 Mycoplasma and Chronic Fatigue, 121 Skeletal Muscle Bioenergetics, 122 Sarcoidosis and Lingual Abnormalities, 122 Brainstem Dysregulation Syndrome, 123 Microsporidia Infection, 124 Organophosphate-Induced Delayed Neurotoxicity, 124 Chemically Induced Porphyria, 125 Fibromyalgia, 125 Somatization Disorder, 125 Summary, 126 6. INFORMATION SYSTEMS............................................................ Overview, 128 Criteria for a Research-Oriented Health Information System, 130 Persian Gulf War Health Information Systems, 131 Health Information Systems for the Future, 133 Conclusions, 137 REFERENCES Xl 117 .......... 128 ....... 141

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. ~ X11 APPENDIXES A. B. C. D. Invited Presentations.......................................... E. Other Groups Reviewing Persian Gulf War Veteran Health Issues ... List of Research and Related Activities on Health Problems of Persian Gulf War Veterans ... G. Selected DoD, Anny, Navy, Air Force, and DVA Databases Relevant Sections of Public Law 102-585........ Statement of Task Committee Meetings and Individuals Providing Information..... ACRONYMS CONTENTS ...159 ...164 ...165 ..168 ......... 171 .175 .184 .189