8
CONCLUSIONS AND RECOMMENDATIONS

The committee was established to review, evaluate, and summarize the peer-reviewed scientific and medical literature regarding the association between deployment-related stress and long-term health effects in Gulf War veterans. This chapter summarizes what the literature collectively tells us about physiologic, psychologic, and psychosocial effects seen in veterans as a result of deployment.

QUALITY OF THE STUDIES

The epidemiologic and other studies reviewed by the committee varied in quality. A major limitation in virtually all the studies reviewed by the committee, except some studies on posttraumatic stress disorder (PTSD), was the lack of an assessment of the perception of stress experienced by the military personnel during deployment to a war zone. The studies that assessed deployment stressors tended to use scales, such as the Combat Exposure Scale, that ascertain whether an exposure to a given stressor occurred (and possibly how frequently), but such assessment tools do not query veterans about their perception of the stressor, for example, whether they were very stressed, somewhat stressed, or not stressed at all. The committee is aware that using deployment as a surrogate for deployment-related stress is a less than perfect method for assessing the long-term health effects of deployment to a war zone, but no other acceptable approaches to the problem were evident. The exception is the use of deployment- or combat-related PTSD to indicate exposure to a war-zone trauma.

Few studies met the criteria established by the committee for a primary study. The requirement that the disease or other adverse effect in question be diagnosed through an appropriate examination or diagnostic instrument meant that many studies, although large and representative of the veteran population, were considered not to be primary studies because they relied on self-reports of symptoms or medical conditions. Other well-done studies involved small sample sizes or used nonstandardized measures. Prior life experiences known to be modifiers of health effects were infrequently assessed. Researchers that compared the accuracy of self-reports with objective measures, such as physical examinations or medical records, often found conflicting results; and the correlation between self-reports and objective measures or diagnoses was sufficiently poor that the committee decided that, although self-reports provided valuable information, a self-report alone was not sufficient to show an association between deployment and a specific health effect. Furthermore, some of the veterans studied were not representative of the entire veteran population being studied, for example, some were receiving medical treatment.



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8 CONCLUSIONS AND RECOMMENDATIONS The committee was established to review, evaluate, and summarize the peer-reviewed scientific and medical literature regarding the association between deployment-related stress and long-term health effects in Gulf War veterans. This chapter summarizes what the literature collectively tells us about physiologic, psychologic, and psychosocial effects seen in veterans as a result of deployment. QUALITY OF THE STUDIES The epidemiologic and other studies reviewed by the committee varied in quality. A major limitation in virtually all the studies reviewed by the committee, except some studies on posttraumatic stress disorder (PTSD), was the lack of an assessment of the perception of stress experienced by the military personnel during deployment to a war zone. The studies that assessed deployment stressors tended to use scales, such as the Combat Exposure Scale, that ascertain whether an exposure to a given stressor occurred (and possibly how frequently), but such assessment tools do not query veterans about their perception of the stressor, for example, whether they were very stressed, somewhat stressed, or not stressed at all. The committee is aware that using deployment as a surrogate for deployment-related stress is a less than perfect method for assessing the long-term health effects of deployment to a war zone, but no other acceptable approaches to the problem were evident. The exception is the use of deployment- or combat-related PTSD to indicate exposure to a war-zone trauma. Few studies met the criteria established by the committee for a primary study. The requirement that the disease or other adverse effect in question be diagnosed through an appropriate examination or diagnostic instrument meant that many studies, although large and representative of the veteran population, were considered not to be primary studies because they relied on self-reports of symptoms or medical conditions. Other well-done studies involved small sample sizes or used nonstandardized measures. Prior life experiences known to be modifiers of health effects were infrequently assessed. Researchers that compared the accuracy of self-reports with objective measures, such as physical examinations or medical records, often found conflicting results; and the correlation between self-reports and objective measures or diagnoses was sufficiently poor that the committee decided that, although self-reports provided valuable information, a self-report alone was not sufficient to show an association between deployment and a specific health effect. Furthermore, some of the veterans studied were not representative of the entire veteran population being studied, for example, some were receiving medical treatment. 317

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318 GULF WAR AND HEALTH Many of the studies were cross-sectional and so could not fully assess symptom duration and chronicity, latency of onset, and prognosis; this is an important limitation because many of the long-term outcomes assessed in this report, such as coronary heart disease and cancer, have latent periods of decades. Some studies of veterans of World War II, the Korean War, and the Vietnam War were longitudinal and allowed an assessment of the health of veterans over time. Finally, many of the studies looked at a variety of exposures of deployed personnel, particularly those of the Gulf War, and this makes it difficult to distinguish specific effects from any one of the multitude of exposures. The committee did not consider the effect of many co-occurring exposures of Gulf War veterans, such as exposure to oil-well fires, pyridostigmine bromide, and vaccines and, for Vietnam veterans, Agent Orange. Therefore, because this report considered the agent of interest—deployment to a war zone—as the only exposure, it may have reached conclusions different from those of other Gulf War and Health reports, particularly Volume 4: Health Effects of Serving in the Gulf War, and Veterans and Agent Orange reports. Several large-scale, nationally representative studies of veterans have been conducted, most notably the Vietnam Experience Study (CDC 1988), which compared Vietnam theater and Vietnam-era veterans for a multitude of health and psychosocial end points; the National Vietnam Veterans Readjustment Study, which made similar comparisons (Jordan et al. 1992; Kulka et al. 1990); the National Health Survey of Gulf War Era Veterans and Their Families (Eisen et al. 2005; Kang et al. 2000); the studies of Australian Gulf War veterans (Ikin et al. 2004; Kelsall et al. 2004) and Danish Gulf War peacekeepers (Ishoy et al. 1999); the hospitalization studies of Gulf War veterans (Gray et al. 1996, 2000); and the Department of Veterans Affairs (VA) Normative Aging Study, which has followed World War II and Korean War veterans since 1961. Those and other studies that evaluated specific health effects formed the backbone of the committee’s assessment of the association between deployment-related stress and various health effects. Many other studies also dealt with large populations of veterans, such as the study of Canadian Gulf War veterans by Goss Gilroy Inc. (1998) and several studies of UK Gulf War veterans, but, although helpful, they used self-reports of symptoms and medical conditions to reach their conclusions. The committee did not consider symptom reporting alone to be sufficient evidence of a health effect in veterans; it required objective measures of a medical condition or a physician’s diagnosis or assessment. OVERVIEW OF HEALTH EFFECTS The experimental literature on stress in both animals and humans suggests that exposure to a stressor initiates a cascade of biologic mechanisms that result in short-term and long-term consequences. In most people, once the stressor is removed, the stress response ceases and the body returns to normal; we consider such a stress response “adaptive.” In some people, however, the stress response does not turn off when the stressor is no longer present, and it becomes “maladaptive” because the body continues to produce stress hormones and other chemical mediators that eventually result in deterioration of normal physiologic processes. The prolonged or chronic stress response can affect virtually all organ systems. Most research has focused on effects in the brain, the cardiovascular system, the gastrointestinal tract, the endocrine system, and the immune system, and the literature on the effects of stress in the general population suggests that chronic stress results in adverse health effects. The epidemiologic literature

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CONCLUSIONS AND RECOMMENDATIONS 319 reviewed by the committee, however, did not demonstrate the array of effects seen in the experimental literature. The epidemiologic literature on deployed vs nondeployed veterans yielded sufficient evidence of an association between deployment to a war zone and psychiatric disorders, including posttraumatic stress disorder (PTSD), other anxiety disorders, and depression; alcohol abuse; accidental death and suicide in the first few years after return from deployment; and marital and family conflict, including interpersonal violence. For several health and psychosocial effects—such as unexplained illness, drug abuse, chronic fatigue syndrome, gastrointestinal symptoms consistent with functional gastrointestinal disorders, skin diseases, incarceration, and fibromyalgia and chronic widespread pain—there was limited and suggestive evidence of an association. For the majority of health effects, the epidemiologic data were insufficient or too inconsistent to determine whether an association existed. The committee also found that deployed veterans report more symptoms and medical conditions and poorer health than veterans who were not deployed, particularly those deployed veterans with PTSD. The prevalence and severity of PTSD was associated with increased exposure to combat. The conclusions reached by the committee regarding various health and psychosocial effects are presented in Table 8-1. TABLE 8-1 Summary of Findings Regarding the Association Between Deployment to a War Zone and Specific Health and Psychosocial Effects Sufficient Evidence of a Causal Association Evidence from available studies is sufficient to conclude that there is a causal relationship between deployment to a war zone and a specific health outcome in humans. The evidence is supported by experimental data and fulfills the guidelines for sufficient evidence of an association (below). The evidence must be biologically plausible and satisfy several of the guidelines used to assess causality, such as strength of association, dose-response relationship, consistency of association, and temporal relationship. • No effects. Sufficient Evidence of an Association Evidence from available studies is sufficient to conclude that there is a positive association. That is, a consistent positive association has been observed between deployment to a war zone and a specific health outcome in human studies in which chance and bias, including confounding, could be ruled out with reasonable confidence. For example, several high-quality studies report consistent positive associations, and the studies are sufficiently free of bias and include adequate control for confounding. • Psychiatric disorders, including PTSD, other anxiety disorders, and depressive disorders. • Alcohol abuse. • Accidental death in the early years after deployment. • Suicide in the early years after deployment. • Marital and family conflict.

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320 GULF WAR AND HEALTH TABLE 8-1 Continued Limited but Suggestive Evidence of an Association Evidence from available studies is suggestive of an association between deployment to a war zone and a specific health outcome, but the body of evidence is limited by the inability to rule out chance and bias, including confounding, with confidence. For example, at least one high-quality study reports a positive association that is sufficiently free of bias, including adequate control for confounding, and other corroborating studies provide support for the association (corroborating studies might not be sufficiently free of bias, including confounding). Alternatively, several studies of lower quality show consistent positive associations, and the results are probably not due to bias, including confounding. • Drug abuse. • Chronic fatigue syndrome. • Gastrointestinal symptoms consistent with functional gastrointestinal disorders, such as irritable bowel syndrome or functional dyspepsia. • Skin disorders. • Fibromyalgia and chronic widespread pain. • Increased symptom reporting, unexplained illness, and chronic pain. • Incarceration. Inadequate/Insufficient Evidence to Determine Whether an Association Exists Evidence from available studies is of insufficient quantity, quality, or consistency to permit a conclusion regarding the existence of an association between deployment to a war zone and a specific health outcome in humans. • Cancer. • Diabetes mellitus. • Thyroid disease. • Neurocognitive and neurobehavioral effects. • Sleep disorders or objective measures of sleep disturbance. • Hypertension. • Coronary heart disease. • Chronic respiratory effects. • Structural gastrointestinal diseases. • Reproductive effects. • Homelessness. • Adverse employment outcomes. Limited/Suggestive Evidence of No Association Evidence from well-conducted studies is consistent in not showing a positive association between exposure to a specific agent and a specific health effect after exposure of any magnitude. A conclusion of no association is inevitably limited to the conditions, magnitudes of exposure, and length of observation in the available studies. The possibility of a very small increase in risk after exposure studied cannot be excluded. • No effects.

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CONCLUSIONS AND RECOMMENDATIONS 321 RECOMMENDATIONS The committee acknowledges that the VA and the Department of Defense (DoD) have expended enormous effort and resources in attempts to address the numerous health issues related to veterans. The information obtained from those efforts, however, has not been sufficient to determine conclusively the origins, extent, and long-term implications of health problems associated with veterans’ participation in war. The difficulty in obtaining useful answers, as noted by numerous past Institute of Medicine committees and the present committee, is due largely to inadequacies in predeployment and postdeployment screening and medical examinations and to lack of recording of stressors to which deployed personnel are exposed. The committee recommends that DoD conduct comprehensive, standardized predeployment and postdeployment evaluations of medical conditions, psychiatric symptoms and diagnoses, and psychosocial status and trauma history. Predeployment evaluation would serve two purposes. First, it would help to identify at-risk personnel who might benefit from targeted intervention programs during deployment—such as marital counseling, medication for psychiatric or other disorders, or psychologic counseling and therapy—which might eliminate or minimize future problems. Second, such evaluations would establish a baseline against which later health and psychosocial effects could be measured. Postdeployment assessment would also serve two purposes. First, it would provide data that could be analyzed to determine the long-term consequences of deployment-related stress and its modifiers; the committee recommends that postdeployment assessments be made shortly after deployment and at regular intervals thereafter (such as every 5 years) to measure the health and psychosocial status of veterans as they age. Second, such assessments would allow VA and DoD to implement intervention programs to assist veterans in adjusting to postdeployment life. The initial assessment after deployment should also ask the veterans what situations, events, or conditions they found to be most stressful during deployment. Knowing which veterans experienced the most stress and recognizing the possible modifiers and consequences of that stress would enable VA and DoD to target prevention and intervention programs to those at greatest risk for adverse effects. The committee further recommends that any longitudinal assessments also be conducted in a representative group of nondeployed veterans to allow appropriate comparisons between deployed and nondeployed veterans regarding health and psychosocial effects. REFERENCES CDC (Centers for Disease Control and Prevention). 1988. Health status of Vietnam veterans. I. Psychosocial characteristics. The Centers for Disease Control Vietnam Experience Study. Journal of the American Medical Association 259(18):2701-2707. Eisen SA, Kang HK, Murphy FM, Blanchard MS, Reda DJ, Henderson WG, Toomey R, Jackson LW, Alpern R, Parks BJ, Klimas N, Hall C, Pak HS, Hunter J, Karlinsky J, Battistone MJ, Lyons MJ. 2005. Gulf War veterans’ health: Medical evaluation of a U.S. cohort. Annals of Internal Medicine 142(11):881-890. Goss Gilroy Inc. 1998. Health Study of Canadian Forces Personnel Involved in the 1991 Conflict in the Persian Gulf. Ottawa, Canada: Goss Gilroy Inc. Department of National Defence.

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322 GULF WAR AND HEALTH Gray GC, Coate BD, Anderson CM, Kang HK, Berg SW, Wignall FS, Knoke JD, Barrett- Connor E. 1996. The postwar hospitalization experience of U.S. veterans of the Persian Gulf War. New England Journal of Medicine 335(20):1505-1513. Gray GC, Smith TC, Kang HK, Knoke JD. 2000. Are Gulf War veterans suffering war-related illnesses? Federal and civilian hospitalizations examined, June 1991 to December 1994. American Journal of Epidemiology 151(1):63-71. Ikin JF, Sim MR, Creamer MC, Forbes AB, McKenzie DP, Kelsall HL, Glass DC, McFarlane AC, Abramson MJ, Ittak P, Dwyer T, Blizzard L, Delaney KR, Horsley KW, Harrex WK, Schwarz H. 2004. War-related psychological stressors and risk of psychological disorders in Australian veterans of the 1991 Gulf War. British Journal of Psychiatry 185:116-126. Ishoy T, Suadicani P, Guldager B, Appleyard M, Hein HO, Gyntelberg F. 1999. State of health after deployment in the Persian Gulf. The Danish Gulf War Study. Danish Medical Bulletin 46(5):416-419. Jordan BK, Marmar CR, Fairbank JA, Schlenger WE, Kulka RA, Hough RL, Weiss DS. 1992. Problems in families of male Vietnam veterans with posttraumatic stress disorder. Journal of Consulting and Clinical Psychology 60(6):916-926. Kang HK, Mahan CM, Lee KY, Magee CA, Murphy FM. 2000. Illnesses among United States veterans of the Gulf War: A population-based survey of 30,000 veterans. Journal of Occupational and Environmental Medicine 42(5):491-501. Kelsall HL, Sim MR, Forbes AB, Glass DC, McKenzie DP, Ikin JF, Abramson MJ, Blizzard L, Ittak P. 2004. Symptoms and medical conditions in Australian veterans of the 1991 Gulf War: Relation to immunisations and other Gulf War exposures. Occupational and Environmental Medicine 61(12):1006-1013. Kulka RA, Schlenger WE, Fairbank JA, Hough RL, Jordan BK, Marmar CR, Weiss DS. 1990. Trauma and the Vietnam War Generation: Report of Findings from the National Vietnam Veterans Readjustment Study. New York: Brunner/Mazel Publishers.