Click for next page ( 15


The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 14
1 Introduction On August 2, 1990, a large Iraqi armed force invaded the independent nation of Kuwait. Five days later, U.S. troops began deployment in Operation Desert Shield, and within 2 months, 200,000 troops had been added to those already in Southwest Asia (SWA). By February 1991, more than 500,000 U.S. troops were in the field, facing the Iraqi army. Intense air attacks against the Iraqi armed forces, beginning on January 16, 1991, opened the phase of operations known as Operation Desert Storm (ODS). ODS ended after a brief, but destructive (to the Iraqi forces), ground war from February 24 to February 28, at which time Iraqi resistance was largely ineffective and peace was restored. The number of U.S. troops in the area then declined more rapidly than it had grown By June 1991, fewer than 50,000 U.S. troops remained. The total number of U.S. military personnel present at one or another time during this interval of Operation Desert Shield/Desert Storm (ODS/S) was about 697,000. The U.S. troops deployed in this war, compared with other conflicts, included a higher proportion of those who were older, were from reserve and guard units, or were female. Although the ground war was short, U.S. service persons experienced several kinds of major, sometimes quite unusual stresses in addition to limited combat. Some of these were physiological, but many were from recognized environmental and external agents such as diesel fumes; microbes; the hostile, hot sandy desert environment; vaccines; oil well fires; and specific occupational exposures. However, there were also potent psychological stresses of several kinds. One was the sudden disruption of lives of large numbers of persons, including family strains when military reserves were suddenly called to active duty. A second was the 14

OCR for page 14
INTRODUCTION 15 unfamiliar character of the region and the requirement that U.S. military personnel have virtually no interaction with the indigenous populations. A third was the very primitive conditions into which some troops were placed. Such basic matters as permanent structures for living or even tents, frequent hot meals, laundry, and recreation were not widely available until near the peak of the military buildup. Other stresses on service personnel came from personal reactions to the very success of the brief war, including the immense destruction visited on the whole nation of Iraq. An additional stressor, unique to this war, was the virtually immediate news reporting of the progress of the war and the ability of those at home to share the images and resulting concerns. This new level of detail in reporting and immediacy of communication intensified the impact of the war experience for those in the field. The dangers from Soviet-designed surface-to- surface (SCUD) missiles were well known. In addition, reports, training, and widespread news related to the "virtual certainty" that chemical and biological warfare (CBW) agents would be used by Iraq in the Gulf theater served to raise levels of apprehension. The experiences of service personnel were nearly as varied as the individuals deployed, and individuals have responded to their experiences in different ways. The majority of men and women who served in the Gulf returned home and resumed their normal activities win little noticeable difficulty. For others, however, a wide range of physical, chemical, and psychological stressors and exposures appear to have had health effects disproportionate to the brevity of active combat and the relatively low combat casualty rate. AN EMERGING PROBLEM In April 1991, while troops were still returning home from the Gulf, Congress passed legislation (Public Law [PL] 102-25) requiring the Secretary of Defense and the Secretary of Veterans Affairs to assess the need for rehabilitative services for those participating in Operation Desert Storm who experienced posttraumatic stress disorder (PTSD); to describe available programs and resources to meet those needs; to describe specific plans for treatment of members experiencing PTSD, particularly with respect to any special needs of members of reserve components; and to provide an assessment of needs for additional resources necessary to carry out such plans, with a description of plans for each department (Department of Defense [DoD] and Department of Veterans Affairs [DVA]) to coordinate treatment services for PTSD with the other. This early action resulted in several DVA projects that are cited in Appendix F of this report. There were also general concerns about possible health effects of exposure to the oil well fires, and as early as April 1991, DVA developed a Persian Gulf Health Registry (PGHR) examination to provide a clinical work-up for veterans

OCR for page 14
16 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR concerned about possible Persian Gulf (PG) service-related illnesses. The DVA registry was later mandated in PL 102-585 (Appendix A) as the DVA Persian Gulf War Veterans Health Registry, to include all who served in the Gulf (whether their present status was active, reserve, or National Guard, including those who left the service). This law (PL 102-585) also expanded previous legislation (PL 102-90, December 1991) mandating that the DoD registry of troops exposed to burning oil well fires include not only those exposed to fires but also all who served in the SWA theater of operations during the Persian Gulf War (PGW). However, the registries were not designed to answer questions about health complaints such as those that soon started to emerge from some veterans who had served in the POW. In January 1992, there were reports from the 123rd Army Reserve Unit in Indiana of unexpected signs and symptoms that could not easily be explained.2 This cluster of reports was investigated by researchers from the Walter Reed Army Institute of Research (WRAIR), who found no common exposures among these reserve troops that could account for the signs and symptoms reported (DeFraites et al., 1992~. This "outbreak" was reported in the news media and received considerable attention. Veterans in other units also began to report their own signs and symptoms, often including serious fatigue, joint pains, headaches, and sleep complaints. As reports of such illnesses and individual complaints increased, so did public concern about a "mystery illness" or "Gulf War Syndrome" (GWS) associated with service in the PG. Both DoD and DVA were involved from the beginning in tracking and investigating these reports of unexplained signs and symptoms. Efforts in both clinical care and research were initiated, and these have grown in size, complexity, and number. The DVA's PGHR was initially associated with three referral centers (Washington, D.C.; Houston, Texas; and West Los Angeles, California) that moved toward standardized and extensive protocols and procedures in 1994. Beginning in June 1994, DoD started a clinical evaluation (Comprehensive Clinical Evaluation Program [CCEP]) specific to active duty troops and modeled abler DVA's referral center examinations. An additional referral center in Birmingham, Alabama, was added by DVA in 1995. Research and clinical activities related to a possible GWS and to over health consequences of service in the POW have multiplied to the point that it is now becoming difficult to keep track of all of the research programs, clinical evaluations, and special treatment efforts. We sometimes use the term "veteran" for those who served in the PG but may still be on duty elsewhere; sometimes the term refers to those who have left military service. 2We generally use "symptoms" to refer to subjective experiences (such as pain or fatigue) described by patients and "signs" to refer to objective findings (such as reduced lung capacity or abnormal reflexes) that a trained observer can detect, perhaps with help from the laboratory.

OCR for page 14
INTRODUCTION 17 Speculation about the existence and possible causes of a GWS have involved several federal agencies and numerous research investigators. Many expert opinions have been offered, and a considerable amount of money has been spent. The designation of GWS itself has been controversial. Even without the stress of war, among approximately 697,000 people over a period of several years, there will be poorly understood ailments and a number of obscure diseases. Beyond these, stress alone can lead to serious illness and disability, often chronic. For example, in comparing long-term outcomes in Japanese atomic bomb survivors with those in Japanese persons who were not exposed, Schull (1996) recently noted that "these studies have shown that as a group the survivors have anxieties not shared with Japanese who were not exposed. They often complain of what has been termed hibakusha, bura-bura the occurrence of lingering fatigue and medically ill-defined symptoms for which no biological basis could be found." PANELS AND COMMITTEES As initial actions described in the previous section were being undertaken by DoD and DVA, White House and congressional interest and involvement also grew rapidly. A number of committees or special groups were established to inspect, review, or evaluate various aspects of the PG veterans health issue (Appendix E). One of the first of these committees met in May 1993. In response to a growing concern that PG veterans were experiencing unexplained illnesses, DVA held a meeting of an informal "blue-ribbon panel" of experts. The group was subsequently chartered (October 8, 1993) as the PG Expert Scientific Committee to advise the DVA Assistant Chief Medical Director for Environmental Medicine and Public Health, and subsequently the DVA Undersecretary for Health, about medical findings affecting PG veterans. The committee was charged to review all aspects of patient care and medical diagnoses and to provide professional consultation as needed. The DVA committee could advise on other areas involving research and development, veterans benefits, and training for patients and staff. The newly chartered committee, chaired by Dr. Eula gingham, University of Cincinnati, first met in February 1994, approximately once per quarter through 1995, and once in 1996. Previously mentioned legislation (PL 102-585) also directed DVA and DoD to seek an agreement with the Medical Follow-up Agency DUAL of the Institute of Medicine (IOM), one of three major components of the National Academy of Sciences (NAS), to review the collection and maintenance of data on health consequences of the POW, consider reported health outcomes, and recommend appropriate studies.

OCR for page 14
18 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR Experts in biostatistics, epidemiology, general medicine, infectious diseases, neurotoxicology, nutrition, psychiatry, pulmonary health, reproductive health, toxicology, vaccines, and women's health issues were assembled. The work of the committee began when it was funded on October 1, 1993. The committee first met on January 20~21, 1994, and held a total of 14 meetings during the two and a half years it was active (Appendix C). A first report, focused primarily on the research process rather than findings, was released on January 4, 1995 (IOM, 1995a). This second and final report of the committee includes information received and evaluated through May 1996. Also, at the end of 1993, DoD assembled a group of experts to examine reports of illnesses that could not be diagnosed. As requested by the Undersecretary of Defense in December 1993, a task force of the DoD Defense Science Board (DSB) was charged to review scientific and medical evidence relating to long-term health effects of exposure to low levels of neurotoxic agents. The Defense Science Board's Task Force on Persian Gulf War Health Effects first met in December 1993. Dr. Joshua Lederberg of Rockefeller University chaired the proceedings. After the first meeting, the task force requested that the charge be changed to focus deliberations on the cause and effect of the full range of exposures to low levels of chemicals as well as environmental pollutants, endemic biologics, and other health hazards that might affect veterans of the PGW An interim report was released on March 15, 1994; the final report was released in June 1994 (DSB, 1994~. The medical nature and the cause or causes of a GWS remained undefined by the task force. The DSB task force did not find evidence of any specific cause-effect relation between putative exposures and an undefined illness. Furthermore, the DSB task force was convinced that reported illnesses by PGW veterans were not due to chemical or biological warfare agents. On August 31, 1993, President Clinton designated DVA as the lead agency to coordinate all research activities undertaken or funded by the executive branch on the health consequences of military service in the PG theater of operations during the PGW. This coordination, mandated by PL 102-585, includes the DVA, DoD, Department of Health and Human Services (DHHS), and Environmental Protection Agency (EPA). As concern about unexplained illness among PG veterans continued to grow, on January 1994 the secretaries of Defense, Veterans Affairs, and Health and Human Services formed a Persian Gulf Veterans Coordinating Board (PGVCB) to ensure interagency coordination of all efforts both separate and joint-in research, clinical care, and disability determination and compensation for illnesses after ODS/S; to ensure effective and broad application of resources; and to provide means of disseminating information. The research coordination occurs under the activities of the Research Working Group (RWG) of the PGVCB, charged with "assessing the state and direction of research; identifying gaps in factual knowledge and conceptual understanding; identifying testable

OCR for page 14
INTRODUCTION 19 hypotheses; recommending research directions for participating agencies; reviewing research concepts as they are developed; and collecting and disseminating scientifically peer-reviewed information" (PGVCB, 1995b). One of the first activities sponsored jointly by the RWG and the National Institutes of Health (NIH) was a Technology Assessment Workshop held April 27-29, 1994, "The Persian Gulf Experience and Health" (NIH Technology Assessment Workshop Panel, 19949. This two-and-a-half-day workshop considered four questions: (1) What is the evidence for an increased incidence of unexpected illnesses attributable to service in the PGW? (2) If unexpected illnesses have occurred, what are the components of the most practical working case definitions based on existing data? (3) If unexpected illnesses have occurred, what are the plausible etiologies and biological explanations for these unexpected illnesses? (4) What future research is necessary? The panel was unable to develop a definition of GWS that could be used to determine whether there is an association between exposures (plausible etiologies) and outcomes (otherwise unexplained illnesses). It criticized the lack of research and available data and focused its recommendations on (1) a short health questionnaire aimed at all 697,000 people who served in the PGW, (2) a focused hospital-clinical protocol for DoD and DVA to use in their research on chronic fatigue syndrome, (3) designs for cohort and case-control studies of health effects of the PGW, (4) a retrospective cohort study of pulmonary function in veterans, (5) retrospective simulation of exposures of possible health interest, (6) research into potential stressors, (7) development of effective responses to diagnosis and treatment of stress-related conditions, (8) planning for prospective data collection, and (9) further research on leishmaniasis, which had been suggested as a possible cause of illness in PG veterans (NIH Technology Assessment Workshop Panel, 1994~. Our first report criticized the agencies for their lack of coordination (IOM, 1995a). We believe that, since that time, the RWG has made considerable progress in developing a unified federal research plan to examine PG health issues. The group released A Working Plan for Research on Persian Gulf Veterans ' Illnesses in August 1995 (PGVCB, l 995b), which, although "intended to guide federal decision makers in establishing research spending priorities, it is also meant to provide information to members of Congress, the scientific community, the public, and, most importantly, the veterans of the Persian Gulf conflict, about the manner in which the federal government is carrying out the research mandate." This document was scheduled to be updated in the spring of 1996 but was not available for review by this IOM committee. The first version of the RWG working plan was an attempt to put the various research activities currently under way into a structure that reflected possible hypotheses as well as gaps in current research. An earlier version of the RWG working plan had been made available to researchers who were interested in responding to a DoD Broad Area

OCR for page 14
20 HEAL TH CONSEQ UENCES OF THE PERSIAN G ULF WAR Announcement (BAA) requesting proposals for research in three areas mandated by Congress in PL 103-337: epidemiology, effects of pyridostigmine bromide (PB), and clinical research. The three BAAs were announced in May 1995 and generated more than 100 responses, which were reviewed for scientific merit by scientists selected by the American Institute of Biological Sciences (AIBS). These reviews, with respondent's name and affiliation removed, were submitted to the RWG for ranking within areas mandated by law and priorities for PG research as set forth in the working plan. Although recommendations were made in January 1996 by the RWG as to the top 12 proposals to be funded, as of the end of May 1996, the announcements of awards had not been made. Therefore, this committee cannot comment on the scope and quality of work selected, which includes three epidemiologic studies, two studies of the effects of PB, five clinical studies, one environmental study, and one leishmania study (Masher, 1996~. The most recently established official group to review the health concerns of PG veterans is the Presidential Advisory Committee (PAC) on Gulf War Veterans' Illnesses, established by Executive Order 12961, May 26, 1995. The PAC was charged to review research, coordinating efforts, medical treatment, outreach, external reviews, risk factors, and chemical and biological weapons. As of May 1996, PAC had held six full committee meetings and five panel meetings. Speakers invited by PAC have testified on specific topics on which information has been requested. All meetings have included an opportunity for public comment. Meetings have been held across the United States to allow greater participation by PG veterans. An interim report, issued in February 1996 (PAC, 1996a), focused on outreach, medical and clinical issues, research, and chemical and biological weapons. The final PAC report is expected in December 1996. CONCLUSIONS Deliberations of these committees and panels have contributed to public interest in the health concerns of PG veterans. Considerable constituent pressure on members of Congress has resulted in legislation mandating agencies to appropriate funds for individual research projects and legislation mandating broad classes of studies, as described above. The committee stresses that for some of the studies designated in this manner, the quality of the individual study is not the issue, but whether the right studies have been selected for support. Such selection requires considerable technical judgment to ensure that Me most relevant populations are examined, that the research has the maximum power to detect effects, and that the cost-benefit ratio is the best that can be attained. We are concerned by the appropriation of funds for individual scientists who have not had peer-reviewed research protocols or whose protocols have not passed

OCR for page 14
INTRODUCTION 21 funding agency scientific and institutional review boards. Failure to adhere to accepted standards and sidestepping of the peer-reviewed research process can result in inferior, worthless, or even unethical research, leading to the adoption of diagnoses and treatments that are medically and ethically questionable and possibly harmful. CHARGE TO THE COMMITTEE The work of the committee was determined by its charge, which is derived from Section 706 of PL 102-585, in which Congress directed the secretaries of DVA and DoD to seek an agreement with the MFUA of the IOM to review existing scientific, medical, and other information on the health consequences of military service in the PG theater of operations during the POW (see Appendix A). The committee's Statement of Task (Appendix B) was drafted by IOM, DVA, and DoD in response to that legislation. A leper from Representative Sonny Montgomery (Former Chairman, House Committee on Veterans Affairs) and Senator John D. Rockefeller IV (Former Chairman, Senate Committee on Veterans Affairs), received shortly after the committee's first meeting, asked for a broader interpretation of the work of the committee than was in the original charge. The committee has responded to this request by discussing and making recommendations within the context of the charge on issues that may impact the health and related matters of soldiers in future deployments. To meet this charge, the committee heard presentations (Appendix D) and reviewed written materials from representatives of DVA and DoD through May 1996; reviewed relevant scientific literature, protocols, reports of findings, and other documents; held a public meeting; reviewed unsolicited materials received (Appendix C); and attempted through staff updates to keep abreast of relevant PG health-related activities, including the activities of other groups. The committee released a first report in January 1995 with a focus on data and databases, coordination and process, and considerations of study design needs. Little research was under way at that time, and research results were sparse. The first report and this report were written to stand independently, and the recommendations of each are based on the findings and material presented in the individual report. The first report of this committee was critical of the lack of research coordination. This lack appears to have been largely repaired by the activities of the RWG of the PGVCB, to the extent that this committee was able to observe their actions. However, it is difficult for outsiders to make specific and appropriate recommendations on how the DoD and DVA should coordinate future research efforts (as distinct from how to conduct specific research programs and projects), because the two agencies are so different, including differences in their areas of research strength. Although issues of how research

OCR for page 14
22 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR on health outcomes from future conflicts should be coordinated were beyond the scope of this committee's charge, we believe that it is extremely important for DVA and DoD to find strategic solutions to problems of joint research efforts. The committee's charge is specific to DVA and DoD, and the focus of our review of data collection methods and research is specific to those agencies. Terminology used in the report necessarily reflects that used by these sponsors. Many other activities are being conducted by private individuals, but a comprehensive review of that body of work is beyond the scope of our charge. However, to make appropriate and relevant recommendations concerning future research activities, the committee believes that a review of federal research activities and plans is appropriate and within the charge. The committee recognizes and agrees that there are veterans who are sick. They must have proper diagnosis and care for their illnesses, including compassionate and expert attention to the full range of their health concerns. However, it is beyond the scope of this committee's work to evaluate issues related to access, responsibility, quality and scope of health care, or possible impact of compensation policies. We believe that this separation of issues is appropriate and that matters of medical care and compensation should be examined separately from issues related to potential causes of illnesses, their treatment, and their prevention in any future conflicts. RESEARCH AND DATA ISSUES Because the task before this committee is focused so heavily on research and data collection efforts, we discuss herein some issues of research design that will provide a framework for the more detailed comments in subsequent chapters. More extensive discussions of epidemiologic research design and definitions of epidemiologic terms can be found in standard references (Fletcher et al., 1995; Lillienfeld and Stolley, 1994~. As we have indicated, individuals deployed during the PGW were at risk of exposure to a myriad of environmental, occupational, medical, psychological, and battle-related health risks. Some exposures may have occurred in a setting recognized as health threatening; other exposures were unlikely. Some were primarily threats to psychological health; others were threats to physical health. Some potential health effects would be immediate; others would become manifest in the medium term; still others might take years or decades to surface. Within these dimensions, there could be many specific manifestations of symptoms and signs. During and after service in the PGW, veterans did begin to experience adverse health effects. Some were PGW-related. Other individuals would have experienced illness during this period whether or not they were in the PGW, whereas the health complaints of still others might be a result of their PGW service. However, there is no way to determine which

OCR for page 14
INTRODUCTION 23 veterans fall into the former group, and research may shed some light on, but not necessarily prove, which may be in the latter group. The most important clinical goal is to understand and treat individual illness. This is complementary to, but distinct from, scientific and public health goals and should be pursued as appropriate without regard to causes or mechanisms of disease. The scientific and public health goals will require relating various exposures and environments to health outcomes. A better understanding of this relation will of course help in attaining the clinical goal. Achievement of the scientific and public health goals might benefit PGW veterans but also allows for prevention or amelioration of adverse health outcomes for troops deployed in the future and for the general population. However, success in attaining the scientific and public health goals will require reliable and relevant information, scientifically sound analysis and interpretation, and availability of effective treatment and prevention resources and modalities. To provide a framework for our recommendations in Chapter 2 and for the evaluations in subsequent chapters, we outline some key scientific and procedural issues related to health risk assessment goals. Our overarching themes are that reliable and relevant data are essential, that both broad and fine details matter a great deal, and that developing an understanding of the range of uncertainty of a risk assessment, while possibly discomforting, may be of greater importance than highlighting best-guess conclusions. The ultimate goal of a health risk assessment is to help in the control of risk by identifying and quantifying its determinants, understanding differences in susceptibility, and assessing levels of exposure (NRC, 1983, 1993~. Some risk factors may be modifiable (e.g., environmental exposures or quality of troop leadership), whereas knowledge of others may be useful in tactical planning (e.g., certain individuals should not be exposed to certain noxious agents). Features of the PGW context as a less than ideal research setting are discussed. These lead to our recommendations in the following chapter and the detailed analysis in subsequent chapters. The PGW as the Less-than-Ideal Setting for Research No health risk assessment is ever undertaken in a fully idealized setting, and our evaluations of the PGW situation should be taken in this context and in recognition of the limitations inherent in any health risk assessment. Conditions and situations in the Gulf theater were not conducive for the proper conduct of research on health outcomes. Some of the problems encountered could be eliminated or ameliorated (databases can be, and are being, improved); for others, progress will be difficult (personal exposures in the theater of operations were not measured and cannot be reconstructed); still others are the inevitable consequence of the early phases of any scientific investigation (no agreed

OCR for page 14
24 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR disease definition, poorly formulated or nonexistent hypotheses leading to poorly collected data, or the absence of data on potentially important inputs and outputs). As the committee noted in its first report (IOM, 1995a), initial research efforts were poorly organized both strategically (what studies could and should be conducted) and tactically (how they should be conducted). For many data collection and analysis activities, no reference population was available (e.g., the registries or outbreak studies), predeployment demographic information on health and medical interventions such as vaccinations was incomplete and possibly inaccurate, there was little standardization and operationalization of data on disease symptoms and signs, follow-up was difficult and incomplete (DoD and DVA databases did not communicate effectively), very little personalized exposure information was available, and changes over time made some data unavailable and reduced or modified possible reference populations. Defining relevant control groups and obtaining data for them were very difficult. The full range of potential biases (selection bias, follow-up bias, dropout bias, observation bias, ascertainment bias, and recall bias) was operating. These problems further limit the ability of even the most expert and well-funded investigation to identify health outcomes linked to specific exposures or risk factors. These and other issues are discussed in detail in subsequent chapters. One example of the challenges posed by the POW situation is associated with cluster identification. There are specific problems associated with studies of "clusters" of some illnesses (Rothman, 1990) (also called outbreak studies or "hot pursuit" studies, characterized as fast, preliminary investigations). Even if the disease is well defined and its diagnosis is properly operationalized, clusters cannot be used to evaluate causation because it is virtually impossible to identify a reference population. Clusters will arise in the absence of causation; indeed they are inevitable in any large and complex collection of study participants and data. It is the task of the investigating analyst to sort out clusters that occur by chance Tom those that occur as a result of some exposure of interest. Clusters sometimes arise, are publicized, generate interest, and often lead to the collection of"cases" (numerator data) that are poorly defined with little knowledge of populations at risk (denominator data). Clusters can play an important role in helping to formulate hypotheses for subsequent studies, and initial reports from sick PG veterans were the starting point for certain types of questions asked in early PG research surveys for example, prevalence of fatigue, headache, muscle aches, and weakness. However, neither well- documented clusters nor moving stories of personal tragedy ("clusters" of one) can establish a cause-effect link between some experience or exposure and a health outcome.

OCR for page 14
INTRODUCTION 25 Where Do We Go from Here? The foregoing paints a rather bleak portrait of the PGW context for health risk assessment. This pessimism is in some ways warranted, but several positive developments could help in evaluating the PGW deployment and any future deployments. Several good research studies are now under way; attempts are being made to link potential exposures with troop locations; information systems are being improved with regard to data capture (including in-theater tracking), data quality, and intersystem linkages; and the clinical registries of DVA and DoD are obtaining standardized, relevant data. Even when considering the difficulties and cautions in interpreting research as described above, the committee believes that there is a sound basis for epidemiologic studies, as well as basic science studies, relevant to an understanding of health consequences of service in the PGW. Specific recommendations about the nature of those studies are presented in Chapter 2. A list of acronyms is provided to assist the reader. Each chapter begins with an "Overview" that summarizes the major points in that chapter.