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4 Health Outcomes OVERVIEW This chapter reviews the empirical evidence available to the committee through May 1996 regarding the health experience of Persian Gulf War (POW) veterans and potential risk factors for adverse health experiences. With the broad question of what adverse health consequences veterans have suffered as a result of their service, the range of relevant experiences is also very broad. The strength of evidence for or against increased risks of specific health outcomes among those who served in the Persian Gulf (PG) depends in part on what research studies have been conducted, and hence on numerous explicit and implicit decisions made by large numbers of research investigators and funding agencies? often acting individually with little perspective on overall needs and priorities. As a result, the research record is of uneven depth and quality. Our task is to summarize the data available to date that appear relevant to our charge of examining possible health consequences of POW service and to recommend the nature of future studies that would provide more and better-answers to this question. Although medical scientists often can use clinical data and individual reports of health experiences to identify areas of concern, such data and reports cannot in themselves provide proof of cause and effect about the health outcomes of POW service. No matter how well documented an illness may be, or how moving a personal story, unexplained illnesses also occur in the civilian population and in troops not deployed to the Gulf. A basic question regarding 67

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68 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR the connection between illness in veterans and their service is not whether specific illnesses or adverse health experiences occurred, but whether the frequency or severity of such outcomes was increased over what occurs in otherwise similar populations that were not in the PG. Battle injuries are universally recognized as a hazard of war. Diseases and infections historically have produced casualties in past wars. Veterans from every war have suffered stress-related symptoms variously known as shell shock; battle fatigue; combat exhaustion; traumatic neurosis; and, since 1980, posttraumatic stress disorder (PTSD). In addition, service members on active duty are subject to the same health hazards as the civilian population, although not necessarily to the same degree: accidents, cancer, heart attacks, stroke, and the like. With the exception of imbedded depleted uranium (DU) fragments and possibly leishmaniasis, very few illnesses or injuries were clearly connected to EG service. However, this committee was convened, in part, in response to congressional concern that there might be something unique to the PG region or to the war fought there that resulted in specific illnesses, some even becoming manifest long after veterans had left that region. Over time, the military services, the Department of Veterans Affairs (DVA), and other federal agencies have expanded the scope and scientific rigor of investigations into the health of PGW veterans in an effort to systematically develop a body of knowledge about their health experiences and risks associated with exposures described in the previous chapter. The committee and other investigators are seeking to determine whether the risk of illnesses was increased among PGW veterans and what research should be carried out to make such determinations. In this overview, we make some general observations about the strengths and limitations of the evidence as a whole. The range of possible PGW-related health effects that can be studied at this time is intrinsically limited. Illnesses and symptoms that occurred during the deployment and were transient in nature were not studied or monitored systematically then and are very difficult or impossible to study retrospectively now. For example, possible temporary decrements in lung function associated with exposure to pollutants from the oil well fires were not evaluated at the critical time and are not very amenable to study now, although they may be important. Likewise, health effects that first come to attention years after the precipitating exposure cannot easily be studied. Many of the known causes of chronic diseases, such as cancer and coronary artery disease, operate over longer periods than have passed since the PGW and, therefore, cannot yet be evaluated in Gulf War veterans. For example, it is commonly believed that most cancers have a minimum 10-year latent period between exposure and detection of the first extra cases of disease. Thus, although no excess adverse cancer effects have yet been reported, delayed effects that have not yet come to light are still possible. What can be examined now are effects that appear early and are

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HEALTH OUTCOMES 69 persistent or become manifest at some time up to several years after the relevant exposure. Concerns about unusual illnesses among PGW veterans arose initially through reports of individuals and then through "outbreak" studies, in which teams of epidemiologists studied groups of soldiers who reported a high prevalence of a cluster of symptoms later proposed to be characteristic of a "Gulf War Syndrome." To provide some support to those veterans concerned about their health, to enable them to receive a clinical work-up, and to gather information on a possible connection to service in the PG, the DVA and the Depa~l~ent of Defense (DoD) created registries and voluntary referral programs for troops, including DVA's National Referral Center and PG Health Registry (PGHR) and DoD's Comprehensive Clinical Evaluation Program (CCEP). Veterans who have voluntarily participated in these registries have not been found to have any unusual rates of diagnosable conditions (DoD, 1996; Kang, 1996; Kang et al., 1995) but do report a pattern of symptom complaints similar to that seen in the outbreak studies. The registries also share the scientific limitations of the outbreak studies, in that participants are self-selected, symptoms are self-reported, exposures are self-reported and could not be validated, and there is no suitable control group. Because of these limitations, the committee has concluded that the information on veterans' health that exists in the registries cannot serve alone as a basis for scientific study of the health effects of the PGW. The committee does consider these registries and their affiliated clinical referral programs as useful in assisting veterans who need clinical services and possibly useful as a source of hypotheses regarding the nature and extent of health problems experienced by PGW veterans. The DVA and various units of the DoD also have undertaken a variety of scientific studies of the health status of PGW veterans. The number and scope of these studies have increased rapidly over the past several years, but few studies had been completed as of May 1996. Findings of several of the completed studies are summarized in this overview. A more complete discussion of these studies and of studies planned or under way is provided in subsequent sections of this chapter, and a listing of research completed, under way, and planned is included in Appendix F. Most of these studies are limited by the absence of detailed exposure information related to individual troops or units. Consequently, studies have had to be designed to seek effects that are sufficiently widespread to be evident when comparing troops who served in the Gulf with those who did not (PG-era veterans). If an environmental exposure or experience was sufficiently widespread among PGW troops and if the health effects of that exposure were sufficiently severe, effects on mortality rates during and after deployment might be demonstrated. To investigate this question, DoD and DVA individually

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70 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR undertook a study of mortality rates of deployed troops and appropriate comparison groups. These studies of mortality rates during deployment documented the rate of battle-related mortality, and both studies found increased rates of death due to accidents and unintentional injury. Despite isolated findings of slightly increased or decreased cause-specific mortality among the cohort of troops deployed to the PG, the overall finding from these studies was that no disease-specific mortality rate was increased among PGW troops. In summary, these mortality studies provide no evidence for an increase in total mortality in the cohort of 697,000 PG veterans that is consistent with a common health complaint or exposure, although mortality from accidents and unintentional injuries appears to be increased in the PG veteran group. The information provided is, however, of limited value in identifying the nature and extent of health effects of PGW service. These studies provide no information, of course, on health problems that did not result in increased mortality. Moreover, because the entire cohort of troops or veterans is studied without identification of exposure-based subgroups, these studies are intrinsically insensitive to increased mortality in a subset of troops subjected to a specific, so far unidentified, exposure. Finally, the period of follow-up has, thus far, been only 2 years. If they occulted, health effects of PGW service might not affect mortality rates for many years. To gather information about morbidity rates among PGW veterans, the Naval Health Research Center (NHRC) at San Diego has undertaken two studies of hospitalization rates, one in PGW veterans who remained on active duty and a second in residents of California who separated from military service after the PGW. Preliminary findings from the first study found no consistent evidence of increased risk of hospitalization for any cause among PGW veterans compared with nondeployed veterans, even after adjusting for a possible healthy worker effect, as suggested by a 10% lower hospitalization rate of PGW veterans prior to deployment. Strengths of this study included the large sample size, ability to adjust for differences in demographic characteristics of PGW and PGW-era veterans, and completeness of the hospitalization data. Yet this study is also of limited value in assessing the health consequences of the PGW. First, it was not feasible to include any but those who remain on active duty. Evaluation of this limitation may be possible with completion of the study of separated troops residing in California. Furthermore, this second study will permit examination of effects that were not evident until after the PGW. As with the mortality studies, an analysis of hospitalization rates in the entire cohort would be unlikely to detect health effects of exposures that affected a small geographic or occupational subset of the cohort. Nevertheless, the mortality and hospitalization studies, when taken together, provide no evidence of an association between any health experience and environmental exposure of sufficient severity to increase the risk

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HEALTH OUTCOMES 71 of early death or hospitalization for the entire cohort of deployed troops in the 2- year period after deployment. Recognizing that mortality and hospitalization rates may not be affected by an increase in the symptoms described in the outbreak studies of military units, investigators have initiated several studies designed to assess the prevalence of self-reported symptoms among PGW veterans and appropriate comparison groups. At this time, only one population-based survey of veterans is nearing completion (Kaiser et al., 1995~: a survey of all regular Navy Seabees who were on active duty during the PGW deployment and were still on active duty between September 1994 and June 1995. This study found no differences in measures of physical health or symptom rates between troops deployed to the Gulf (N= 527) and those on duty elsewhere (N= 970~. However, Seabee veterans who had been deployed to the Gulf did have higher mean levels of psychological symptom scores. Again, a limitation of this study was the absence of any specific information about exposures experienced by individual troops. The NHRC is now conducting a broader study of active, reserve, and separated Navy Seabees who were on active duty during the era of the PGW. Psychological sequelae are important and somewhat predictable consequences of service in war. We recognize that they can disable otherwise healthy individuals, but psychiatric diagnoses should not be adopted in default of other medical diagnoses. Furthermore, we believe these are war-related illnesses that deserve attention by the military and DVA in terms of both prevention and treatment. Several studies of stress and responses to stress are described below. Many veterans have expressed concern about the possibility of adverse effects on their conception of children subsequent to the PGW. Four pilot studies of reproductive health experiences of PGW veterans have been completed, and three large population studies are now under way. None of the four pilot studies have detected increased rates of adverse reproductive outcomes in PGW veterans. Given the preceding overview, the committee has not identified scientific evidence to date demonstrating adverse health consequences specifically of PGW service other than the documented incidents of leishmaniasis, combat- related or injury-related mortality or morbidity, and increased risk of psychiatric sequelae of deployment. At the same time, the committee recognizes that studies provided to us thus far do not comprise a comprehensive scientific investigation of the health consequences of service in the PGW. In addition to the recommendations for research given in Chapter 2, the committee believes that value to the military services and the country will result from completion of the NHRC reproductive studies, well-designed scientific studies of determinants of vulnerability (and resilience) to stress arising in deployment and combat, investigations of unexplained illnesses and of relatively obscure syndromes (e.g., chronic fatigue syndrome), and research into

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72 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR improved methods to diagnose leishmaniasis. If proposals for such studies are identified through established procedures for peer review, the committee recommends that they be favorably considered for funding. We have organized the accumulated evidence by study type and endpoint into the following sections: mortality studies, hospitalization studies, diagnosed diseases in PG veterans, studies of self-reported symptoms (outbreaks and surveys), adverse reproductive outcome studies, mental health studies, and women's health studies. The research activities known to the committee as of May 1996 are listed in Appendix F. We turn now to a review of the epidemiologic evidence. MORTALITY STUDIES Records of deaths during the period of deployment are available, and the mortality experience of the POW veteran cohort, both during and after deployment, is reviewed in this chapter. Death records are uniquely informative and available, in that without taking any special measures, the information is likely to be very nearly complete and accurate regarding the person and the time of occurrence. Even during the POW itself, both battle casualties (Helmkamp, 1994) and nonbattle casualties (Writer et al., 1996) were comprehensively ascertained. There is a restriction on the types of events that can be suitably monitored through mortality data. Only fatal injuries can be evaluated, and they may or may not follow the same pattern as nonfatal injuries. Diseases with a high case- fatality rate such as lung cancer can also be evaluated through mortality data. However, for some diseases, death is an unusual consequence; examples are arthritis, asthma, and nonmelanoma skin cancer. Relative to mental health, severe depression may be reflected to some extent in suicide mortality, but mortality data may tell us very little about severe nonfatal psychiatric disorders. Although multiple causes of death are often recorded and coded, the interpretation of nonunderlying causes of death is still difficult and uncertain. Not all potentially relevant ancillary causes will be noted, and the extent of completeness may well vary in relation to social and demographic factors and in relation to the source and quality of health care, including military versus nonmilitary providers. The adequacy, accuracy, and detail of mortality data are suitable for some assessments of health risk but not for others. In general, broad categories of fatal disease can be examined with some confidence (e.g., coronary heart disease or suicide), whereas death certificate classifications are less reliable for diseases that are more difficult to diagnose or require more specific classification (e.g., the chronic neurologic diseases or subtypes of leukemia). Two mortality studies of PG veterans have been conducted (Kang and Bullman, 1995; Writer et al., 1996~. Both studies encompass general PG

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HEALTH OUTCOMES 73 veteran populations. Each study includes very large samples. One assessed mortality for veterans up to 2 years after active duty; the other assessed mortality during active duty. Both studies compared troops deployed to the PG with troops deployed elsewhere during the same period. Neither includes information about specific environmental exposures. No excess mortality was observed among PG personnel, with the exception of combat-related deaths and deaths due to accidents and unintentional injury. We do not consider battle deaths (evaluated by Helmkamp, 1994), although we do evaluate wartime nonbattle deaths (described by Writer et al., 1996~. Writer et al. (1996) studied troops with active duty status during or shortly after the POW. All men and women who were on active duty in the PG theater of operations between August 1, 1990, and July 31, 1991, were identified, with demographic information, dates of service in the PG and elsewhere, and date and cause of death. The control group was composed of service personnel stationed elsewhere at the same time. Among the 1,622 total nonbattle deaths during this year, 1,397 occurred in nondeployed service personnel (73 per 100,000 person-years) and 225 occurred in those deployed (85 per 100,000 person-years). More than half (N= 967) of all deaths were due to unintentional injury, with more than half of these (N = 501) being motor vehicle injuries. Other major contributors were deaths from illness (N= 294), suicide (N= 216), and homicide (N= 103~. By using the experience of nondeployed veterans to generate expected mortality rates for those deployed, relative risk (RR) estimates were generated, with adjustment for age. The RR= 1.12 (95% confidence interval [CI] = 0.97- 1.26) for all nonbattle deaths. This means that there were 12% more deaths in PG veterans than in veterans who had not been in the Gulf theater, but that random variation in the number of deaths is readily compatible with any figure from a 3% decrease to a 26% increase. Since this range includes "no difference," evidence for an effect of Gulf service on total mortality is weak. Similarly, RR= l.lS (95% CI = 1.01-1.34) for all injuries; RR= 1.54 (95% CI = 1.32-1.77) for unintentional injury; FOR= 0.34 (95% CI = 0.16-0.63) for suicide; and RR = 1.15 (95% CI = 0.73-1 .73) for a combination of cardiovascular disease and unexpected or undefined causes of death. Subject to the inherent limitations in mortality data noted above and the restricted study period, these data suggest that an increase in unintentional injury was associated with deployment, but most other comparisons were consistent with "no difference." A second major report concerns mortality in the 2 years after the end of hostilities. POW veterans were compared with veterans from the same era who did not serve in the Gulf (Kang and Bullman, 19951. This historical cohort mortality study was conducted among all 695,516 men and women who served in the PG between August 1990 and April 1991 and a sample of 746,291 veterans from the same period who served elsewhere, matched by branch of

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74 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR service and unit type (active, reserve, and guard). The interval of follow-up was May 1, 1991, through September 30, 1993, or date of death, whichever occurred first. The investigators identified 1,765 deaths among PGW veterans and 1,729 deaths in the control group. Age was included in the multivariate analysis to control for possible differences in the distribution of this variable between the two groups. The risk of death was slightly higher among PG veterans who remained on active duty than among other active duty veterans from the same era, with a mortality rate ratio (relative risk) of 1 .15. Several causes of death were reduced, but not significantly, among PG veterans, including infectious disease, cancer, and respiratory disease, whereas a consistent pattern of significantly elevated risk was found for unintentional injuries, including motor vehicle injuries, for which the relative risk estimates were around 1.5. Suicide and homicide rates were similar in the two groups. The overall mortality (RR = 1.47) for female veterans of the PGW was slightly higher than the overall death rate for other women veterans. Investigators also found a significant twofold increase in unintentional injury and motor vehicle injuries, but no significant differences in mortality due to specific illnesses. The relative risks of homicide and suicide were elevated (RR = 2.0 and 1.5, respectively), but these were not statistically significant. The same overall pattern was present but less pronounced among reserves. Kang and Bullman (1995) compared mortality in both PG veterans and PG- era veterans with that in the total U.S. population of the same age and sex and found that for men, total mortality was markedly reduced among both groups of veterans compared with the U.S. population, as were deaths from unintentional injuries and motor vehicle injuries. Both groups of women veterans showed reduced mortality rates compared to those of the general population, with somewhat elevated rates of suicide and motor vehicle injuries for PGW veterans. Both of these studies (Kang and Bullman, 1995; Writer et al., 1996), particularly that of Kang and Bullman (1995), point to injury, both intentional and unintentional, during and after the war as the leading cause of excess mortality among PGW veterans. This is not to say that a potential effect on mortality due to illness has been disproved, only that such an effect could not be demonstrated with 2 years of follow-up. This is an important finding, and further follow-up will be appropriate for evaluating possible differences between groups for medical conditions with longer latency periods. HOSPITALIZATION STUDIES Computerized hospital discharge data provide a resource for assessing whether PGW veterans were at increased risk of hospitalization after the war relative to appropriate comparison groups and for investigating the distribution

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HEALTH OUTCOMES 75 of primary diagnoses as defined at hospital discharge. Because hospital discharge data are collected and reported by individual hospitals, which serve poorly defined populations, studies of hospital discharge rates often focus on geographically defined populations, such as persons who report that their permanent residence is in a specified state. Virtually all hospitalizations of active duty personnel take place in military hospitals, and all military hospitals participate in a hospital discharge record system maintained by DoD. However, hospitalizations that occur after discharge can take place in private; public; VA (Veterans Administration); and for those who are retired, military hospitals, making total case ascertainment extremely difficult. Since the population who served in the Gulf is fairly well defined and a very high percentage of hospitalizations during military service can be recovered among those who remain on active duty, studies of hospital discharge data can provide sound comparisons of hospitalization experience based on large numbers of observations. This minimizes the effect of sampling variability on the findings. Hospitalization records typically provide detailed demographic data that can be used to control for important potential sources of confounding. The data reflect the diagnosis assigned at hospital discharge and are only as accurate as the diagnostic categories used in hospitalization records and the diagnostic evaluations conducted at the hospitals under study. Comparisons of large samples will not provide information about the risk of hospitalization among subsets of the POW veteran population subject to specific exposures or hazards unless exposed populations can be defined. Additionally, military treatment centers may not provide the majority of care for certain health conditions of interest (e.g., obstetric care is often provided in the civilian sector for some of these military groups). Finally, hospitalization studies of those who remain on active duty will be subject to biased ascertainment if health-status- specific discharge rates differ for PG and PG-era veterans. To date, one study of the hospitalization experience of POW veterans has reported preliminary findings (Coate et al., 1995~. These investigators, at the NHRC in San Diego, used a retrospective cohort design to compare prewar and postwar hospitalization rates of 547,076 regular Army, Navy, Marine, and Air Force active duty troops deployed to the PG between August 8, 1990, and July 31, 1991, with those of 618,335 nondeployed veterans. The study sample consisted of all regular service personnel on active duty at the beginning of the study period who were deployed during that period and for whom records were available, and a random sample of nondeployed personnel matched for service. Four periods were selected for study: October 1, 1988, to July 31, 1990 (prewar); August 1, 1991, to December 31, 1991; all of 1992; and January 1, 1993, to September 30, 1993. The period August 1, 1990, to July 31, 1991 (roughly the period of the POW), was not included because of known differences in care between the two groups during that time. In each period, the study was restricted to people who were still on active duty on the first day of

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76 HEAL TH CONSEQ UENCES OF THE PERSIAN G ULF WAR the study period. Hospitalization data were drawn from the DoD hospital discharge records provided by all U.S. military hospitals and were matched to records of service personnel by social security number. Hospitalizations for any cause and with a diagnosis in each of 14 broad ICD-9 (International Classification of Diseases, version 9) diagnostic categories were compared for deployed and nondeployed personnel, both before and after adjustment for demographic characteristics. This study found no increased risk of hospitalization for any cause among PGW veterans compared with nondeployed veterans, even after adjusting for a possible "healthy worker effect." (This is a phenomenon commonly observed in studies of workers, whereby their death and disease rates are lower than those of the general population. Reasons may include favorable health status associated with the ability to find or keep a job, the comprehensive health care offered by some employers, errors in reporting work status, and other factors. In the present context, perhaps it could be called the "healthy veteran effect.") Examination of 14 broad diagnostic categories in each of the three postwar periods found only four instances of possible increased risk of hospitalization among PGW veterans: neoplasms (largely benign), 1991; diseases of the genitourinary system, 1991; diseases of blood and blood-forming organs (mostly anemias), 1992; and psychiatric disorders, 1992. No diagnostic category of hospitalizations was elevated in all three postwar periods. PGW veterans did experience higher rates of hospitalizations for psychiatric disorders. Detailed analysis of these hospitalizations showed an increased risk of hospitalization related to the use of alcohol and drugs. This study (Coate et al., 1995) had several important strengths. The large sample size and availability of demographic data reduced the effects of sampling variation and confounding on the results. Virtually all hospitalizations of active duty personnel (with the possible exception of childbirth) take place in military hospitals and are captured in the hospital discharge data set, so that bias in ascertainment of hospitalizations is not likely to explain the observed results. Limitations of the study include its restriction to regular active duty personnel who remained on active duty throughout the study period. Of the initial cohort of 1,279,931 individuals, 91% remained on active duty on August 1, 1991; 84% remained on January 1, 1992; and 66% remained on January 1, 1993. Increased hospitalization rates among those who left active duty because of their illnesses would not have been detected unless these illnesses had led to hospitalization prior to discharge. Diseases with latency periods longer than 3 years would not be detected by this study, nor would illnesses that did not lead to hospitalization. Increased hospitalizations due to public awareness of the putative Gulf War Syndrome would have been limited to PGW veterans. Since this was not observed, response bias appears not to have appreciably affected the data.

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HEALTH OUTCOMES 77 The team at NHRC also is conducting a study of rates of hospitalization of veterans from all service branches who have separated from active service. This study will compare the hospitalization rates of PGW veterans and a random sample of PGW-era veterans in nonmilitary hospitals in California between 1989 and 1994. The PGW cohort will be defined as military personnel who deployed to participate in the PGW at any time between August 2, 1990, and July 31, 1991. The study population will be further limited to PG veterans who, when deployed, had resided in California for at least 1 year. Prewar hospitalization rates will be collected to compare the predeployment health status of PGW and PGW-era veterans. Hospitalization rates also will be compared to those of active duty personnel. This study has the potential to complement the previously described hospitalization study of the same group of PGW veterans who remained on active duty. It will address the possibility that PGW veterans experiencing adverse health effects of service were differentially separated from service, thereby masking a health impact on the cohort as a whole. The study will provide information on hospitalization rates after separation for about 12% of the PGW cohort, the percentage of troops who satisfy the California residency requirements. Limitations of the study include its inability to identify hospitalizations outside California for the same individual and the possibility that admission criteria differ for nonmilitary hospitals and VA Medical Centers (VAMCs). Despite these limitations, this study will provide information about hospitalization rates after discharge that complement the previously described study of PGW veterans who remained on active duty after the war. It may also help to characterize the potential for differential follow-up in the study of military hospitalizations resulting from earlier separation of veterans experiencing health problems after the war. This is a good plan that may provide a model for future deployments. It will be important for researchers to acknowledge study design limitations as they interpret the findings. A limitation of both mortality analyses and hospital discharge analyses as commonly performed is that they are usually restricted to a single cause of death on the certificate (usually the "underlying cause of death") or a "principal reason for hospitalization." A second limitation of both study designs is that even an examination of the entire PGW veteran cohort would be unlikely to detect the health effects of exposures that affected only a small geographical or occupational subset of the cohort or were rare events. When taken together, however, completed studies of mortality and hospitalization rates of PGW veterans provide no evidence of an association for any widespread or common environmental exposure or other threat to health of sufficient severity to increase the risk of early death or hospitalization among a large segment of the cohort of deployed troops in the 2 to 3 years after deployment.

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106 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR Explanations for gender differences in mental health have included the likelihood that women are socialized to express symptoms whereas men are socialized to suppress expression. Another explanation is that women's experiences of trauma in war were different from those of men. This explanation may be warranted by consideration of data about abuse. As discussed in Chapter 3, an experience unique to women or at least much more prevalent among women who served in the Gulf was exposure to violence and sexual harassment (Wolfe et al. 1992b). Those who reported assault had higher Mississippi Scale scores for PTSD symptomatology, and those reporting assault or physical harassment had higher GSI/BSI scores. There is also evidence that past exposure to violence and abuse, such as childhood sexual or physical abuse, is associated with PTSD. Marlowe (1995) concluded that one could not determine from data collected by DoD whether there were factors that predisposed one to a highly stressed response to combat. He did note that those who were highly stressed before combat were also highly stressed after combat and that those with high psychological symptom scores at the time of the first postcombat study tended to have high scores a year later. These same individuals had high reactions to current life events as well as to ODS events. Factors Enhancing Resilience or Buffering Effects of Stress on Mental Health Sutker et al. (199Sb) compared 97 POW troops with PTSD diagnosis to 484 without psychological distress to determine differences in their personal resources (gender, education, intellectual sophistication, and personality dispositions such as hardiness and coping styles) and environmental resources (perceived social support and family relationship support). She found that less commitment, more avoidance of coping, less family cohesion, and lower social support satisfaction were factors associated with those who developed PTSD diagnoses. DoD studies indicated that the service person's military unit served as a social support mechanism to buffer the effects of exposure to acute and chronic stress on health. Postcombat sharing of experiences within studied units provided a source of aid for coping with the sequelae of war. Shared coping with traumatic events in the field seemed to be more beneficial to soldiers than dealing with such events after returning to the United States (demobilization) (WRAIR, 1992~. As identified by active duty troops deployed to the Gulf from Pennsylvania and Hawaii, sources of support that were somewhat helpful included family, friends, chaplains, and unit members. For reserve troops, similar sources of support were indicated. That report (USAMRMC, 1994) stated that more than 90/O of active duty and reserve troops studied were coping moderately to extremely well 2 years after ODS/S, but 7.8% of the active duty

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HEALTH OUTCOMES 107 deployed felt that they were coping poorly versus 5.5% of active duty nondeployed. Long-Term Mental Health Outcomes Most studies to date have been of short-term acute outcomes. DVA- sponsored studies discussed above, conducted by Wolfe at the Boston VAMC (Wolfe et al., 1993) and Sutker at the New Orleans VAMC (Sutker et al., 1993), indicated persistence of psychological distress among troops for at least 1 year after return from ODS/S. Marlowe (1995) of DoD has followed selected troops for as long as 2 years after return from ODS/S and found that those who were highly distressed before combat were also highly distressed after combat. Thus, these studies have made significant contributions, but follow-up so far is too short to resolve questions about factors associated with the persistence of PTSD symptoms and other types of illness. Symptoms of PTSD in some veterans have persisted for at least two decades after the Vietnam war. Physical Symptoms and Exposure to Stressors Physical symptoms in conjunction with stressors were also studied by DoD. Although physical symptoms do not in themselves signify PTSD or other mental health problems, there is a large literature linking acute and chronic life stress and mental health to future physical morbidities, including gastrointestinal and hyperimmune diseases (Vogt et al, 1994~. A comparison of physical symptoms experienced by deployed and nondeployed active duty and reserve troops indicated that those deployed were more than twice as likely to report head colds, sinus trouble, sore throat, difficulty swallowing, headaches, back problems, stomach upset, muscle aches, aching joints, cough, chills or fever, and other problems. This was the case when demographic factors such as age, rank, education, marital status, and branch of services were controlled (Stretch et al., 1 9951. An algorithm of physical and psychological symptoms was calculated as a proxy indicator for Gulf War Syndrome (GWS) symptoms (Stretch et al., 19953. These included headache, stomach or intestinal upset, muscle aches or cramps, aching joints and bones, weight loss or gain, cough, chills or fever, general level of spirits, level of energy, trouble with memory, pains in the chest or heart, low energy, difficulty getting breath, difficulty concentrating, and feeling weak in parts of the body. Those reporting five or more of the health symptoms and at least one of the psychological symptoms were identified as follows: 178 of troops deployed (12%) and 55 (2.2%) of those not deployed scored high on this index. Of those with high scores on the GWS index, 42% attributed their health problems to ODS/S service, 45% had concern over exposure to oil fires, 36% claimed to have been exposed to oil fires, and 30% met the criteria for possible

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108 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR PTSD diagnosis (Stretch et al., 1995). The authors indicate that the most powerful factor discriminating these multiple-risk groups from those not at high risk was whether or not individuals had been deployed to the Gulf. Investigations by Wolfe and Sutker also addressed the prevalence of somatic symptoms or symptoms with a bodily referent (i.e., pertaining to the body rather than to emotion) among veterans studied immediately after return to the United States and 1 year later. The associations among physical symptoms, stress, and mental health were examined in ongoing studies of Fort Devens reservists. Wolfe et al. (1994) found that women veterans with PTSD At= 40) reported significantly more health symptoms than their counterparts without PTSD (N= 153~. ~ ^'' the to~iow~ng symptoms were reported by 85-100% Of women with PTSD, in decreasing order of prevalence: trouble concentrating, depression, nervousness lack of energy, aches or pains, insomnia, headaches, loss of interests and crying easily. Those with PTSD also reported more _ . ~. ~. 1 1 ~1 combat exposure, less current social support, and more postclep~oyment bite stressors. When all health symptoms were included in a regression model, anxiety and PTSD were significant predictors of health symptoms, but combat exposure was not. Of interest is that PTSD symptoms of emotional numbing and physiologic hyperarousal were significantly related to the number of health symptoms reported. Understanding the connection between psychological and physical symptoms and their relation to exposure to traumatic events requires consideration of the temporal ordering of events and plausible mechanisms. Given the lack of predeployment data for most troops, it is difficult to ascertain the temporal order of events. Some may have experienced traumatic events prior to deployment (e.g., rape or sexual or physical abuse), and some may have had prior illnesses with mental and physical symptoms. The DoD and DVA studies document the cooccurrence of stressors (e.g., combat exposure), PTSD- like symptoms, and physical symptoms, many of which are nonspecific. (Chapter 5 of this report addresses consideration of somatization, chronic fatigue, and multiple chemical sensitivity [MCSl). Those with PTSD after ODS/s have had more severe health symptoms (Stretch et al., 1995; Wolfe et al., 1994). One of the mechanisms proposed to link traumatic events (stressors) with symptoms is the physiologic changes induced as part of the stress response. Studies dating from Selye's classic experiments (Selye, 1956) link stress to changes in the hypothalamic-pituitary-adrenal (HPA) axis hormones, resulting in an increase of glucocorticoid production from the adrenals. Cortisol and other glucocorticoids initiate suppression of immune, metabolic, and neural defensive reactions in response to stress. Over the past two decades, physiologic alterations in response to extreme stress have been studied in humans with PTSD related to a variety of traumatic events (combat exposure, holocaust survivors, rape victims, and survivors of natural disasters). A series

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HEALTH OUTCOMES 109 of studies of hormonal alterations in response to stress has demonstrated persistent biological changes after extreme stress. Findings of lower basal cortisol levels in people with PTSD are opposite to those expected as part of the normative stress response and suggest possible exhaustion of the response. In contrast, exposures of PTSD patients to a novel environmental stressor and exacerbation of comorbid conditions are associated with elevated cortisol levels. Similar responses occur to acute treatment interventions that involve "reliving" exposure to the stressor (Yehuda et al., 1993~. Other studies of PTSD related to abuse show elevated levels of norepinephrine, epinephrine, dopamine, and cortisol (Lemieux and Coe, 1995~. Studies of women who have been sexually assaulted show an increased risk of both medically explained and unexplained symptoms (Golding, 19941. Studies of civilian populations in the Gulf also demonstrate somatic responses to stressors in the war. A telephone survey of the Israeli civilian population found that 38% had somatic reactions to the orders to wear gas masks and move into sealed rooms, but only 20% had somatic responses 12 days later, suggesting adaptation to stress through time. A complex pattern of relationships between expectations about chemical warfare and somatic interactions was evident. Those with specific expectations about future chemical attacks were more likely to have a somatic reaction. Also, women were more likely to react than men. Habituation occurred quickly (Carmeli et al., 1991~. In another telephone survey conducted during the third week of the war, 28% of community residents complained about sleep: 10% had awakenings, 4.5% had difficulty falling asleep, and 13.5% experienced bosh. Women and persons with less education reported more sleep problems (Lavie et al., 19919. Although PTSD may have psychophysiological components, to date the committee has found no published studies linking PTSD with physiologic aspects of stress response or symptoms with physical referents among ODS/S veterans. Future studies elucidating the psychophysiological consequences of extreme stress and their relationship to both mental health and symptoms with bodily referents are needed. Discussion of Mental Health Issues In addition to the literature reviewed above, the committee discussed several psychosocial variables that could influence the incidence of unexplained illnesses among POW veterans. These included the role of suggestion in shaping symptoms and the role of concerns regarding health care. Also discussed were various psychiatric syndromes that include physical symptoms, PTSD, and other psychiatric outcomes, with recognition of He facts that psychiatric diagnoses are not to be made by exclusion and that they are often comorbid. Each is discussed briefly here.

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110 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR Many pervasive and powerful suggestive influences have affected PGW veterans, including attention by the news media, Congress, and peers. Reports in the news media, meetings of veterans groups, and public and congressional hearings have served to draw attention to certain symptoms that may be present in PGW veterans or certain possible exposures. These are strong influences affecting patients' recall and reporting. How such forces affect the symptoms reported is not known, but this could be an important topic to evaluate. Veterans of the PGW returned to a nation in turmoil over health care and its financing. A key question for many veterans was whether DVA would provide the necessary treatment on a service-connected basis; this fear may have been put aside to some extent when legislation determined that unexplained illnesses were service connected, whereas many diagnosed diseases were not. However, this also meant that having a diagnosis did not guarantee treatment if the illness was not considered service connected, especially for reserve and National Guard troops who were left to prove the connection. Some persons suggested to the committee that certain known syndromes and physical illnesses could explain some veterans' undiagnosed illnesses. How these syndromes and illnesses may or may not be connected to purely physical versus psychiatric diagnoses is not well determined in either the scientific literature or the medical community. Some of these hypotheses are discussed later in this report. PTSD may be the most studied and expected of the war-related psychiatric illnesses, but there are others that could be manifest in less well defined ways. Our society has a greater acceptance now than in years past of stress as a cause of impairment, as well as a greater tendency to provide compensation for such impairment (e.g., disability claims, legal settlements, and medical retirements). After the Vietnam War, veterans were more forthcoming than previously in seeking treatment or claiming disability for mental, emotional, or psychophysiological distress. This trend should not be discouraged among PG veterans, whose stressors may include experiences from predeployment through combat to reentry to daily living. Finally, the committee has been concerned that a diagnosis of somatization disorder, PTSD, or other psychiatric illness not be made by default in those cases where a physical diagnosis has not yet been established. Psychiatric diagnoses require specific findings that the disorder is present. Physical illnesses are often accompanied by emotional disturbances or even gross psychopathology, and DSM-IV (APA, 1994) lists some physical illnesses that may present with psychiatric symptoms. A patient whose complaints are not accepted as legitimate over a period of time may also develop symptoms of an adjustment disorder superimposed on the underlying illness, thereby making a basic diagnosis even more difficult.

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HEALTH OUTCOMES 111 WOMEN'S HEALTH STUDIES Approximately 50,000 of the troops deployed to the PG were women. Although women have been present in combat situations during earlier wars (Congress established the Nurse Corps of the Army in 1901 and of the Navy in 1908, and an estimated 5,000-10,000 women served in Vietnam), the number of women in forward combat support positions was uniquely high for the U.S. armed forces during ODS. With the exception of DoD studies conducted in- theater prior to the air war, most studies of the health of PG soldiers include women and men. Findings of these studies are summarized below, and issues related to women's experiences are enumerated along with questions that merit further consideration. The large number of women living in field conditions, working side by side with men, and doing the same work as men under "field expedient conditions" was also unique to this war. These conditions often required work (and exposures) for 16-hour days, 7 days per week, as discussed in Chapter 3. The health of women veterans is a very important issue in light of projections of a 17% increase in women veterans between 1990 and 2010, when women will represent 6.4% of the total U.S. veteran population (Sorensen and Feild, 1994~. In addition, in civilian populations, women's utilization of health services on average exceeds that of men (Nathanson, 1975), sO that the types and number of visits and the use of services could be significantly increased. In addition, women's health has been influenced by a social context in which men played the dominant roles. Issues of leadership or management and training raised by having women serve with men in combat roles also may have significant health effects. Health consequences of combat service for women, gender differences in health, and health issues related to men and women serving in combat situations are all considerations in our recommendations for further action. Health Effects of Combat Service for Women Given the novel experiences noted above and the large number of women deployed in the POW, it is important to determine whether there were health problems unique to women. Because limited data are available to answer this question, the topic requires further study. Long-term follow-up of women veterans who served in ODS is needed. Available data suggest a need for a data collection system that will capture important health services (utilization, needs, and issues) in a way that directs immediate action as well as support for future research. It has been well established in civilian populations that women are more willing to report symptoms and use health services more readily than men for symptoms and conditions that affect both sexes (Nathanson, 1975, 1980~.

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112 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR Thus interpretation of health reports by veterans will require adjustment for gender differences in reporting. Reports from several studies, including the General Accounting Office (GAO) study of women, confirm that women deployed to the PG could and did accommodate to adverse conditions and, in the short term, did not present with more health and hygiene problems than men (GAO, 1993b). Data presented earlier in this chapter suggest some gender differences in symptom reporting in the DVA registry. Pregnancy and certain reproductive system problems (including malignancies such as breast, cervical, and ovarian cancer) are problems unique to women. Pregnancy presents a challenge to women's health under any circumstances and may produce unique health problems in combat situations. In the past, the military has forced women to separate because of pregnancy. Indeed, one of six women in the 1985 Veterans Administration survey of female veterans who entered the military in the post-Vietnam era reported being forced to separate from military service for reasons of pregnancy or having children (VA, 1985~. To date, there are no published reports or studies concerning women who became pregnant while deployed to the PG or the military management of these situations. Pierce (1996) identified a stratified sample of 638 women to study 2 years after the PGW and again 2 years later. The sample included active duty, guard, and reserve Air Force components; those deployed to the Gulf versus elsewhere; and those who were parents, as well as nonparents. General physical health, gender-specific health problems, emotional responses to war, and symptoms common in the unexplained illnesses were surveyed with 97% participation of those located (N= 5254. Women deployed to the PGW reported significantly more general and gender-specific health problems than those deployed elsewhere. Common health problems included skin rash, cough, depression, unintentional weight loss, insomnia, and memory problems. Active duty women reported more general health problems than those in the reserve or guard, despite their younger age. Among those deployed, women who were parents had significantly more health problems. Two years after the PGW, skin rash, depression, unintentional weight loss, and insomnia were significantly more prevalent among those deployed to the Gulf than those not deployed. Four years after deployment, skin rash remained significantly more prevalent among those deployed and cough and memory problems were more prevalent among the deployed. There were no differences in gender-specific health problems 2 years after PGW, but 4 years later, those deployed had a greater prevalence of lumps or cysts in the breasts, abnormal Pap smear results, and headaches. There was a trend for increased prevalence of herpes among those who served in the Gulf for more than 120 days compared with those who served for less than 120 days. Of those deployed to the Gulf, 24% met criteria for PTSD versus 15% of those deployed elsewhere (Pierce, 1996~.

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HEALTH OUTCOMES 113 A final variety of health problems affecting women includes those producing acute episodes of symptoms (e.g., vaginitis) that indicate special personal support needs. A "field doctrine" for medically appropriate and field expedient approaches to contraception is also needed. This includes ensuring continuity while activated of medication (e.g., oral contraceptives) used prior to deployment. Gender Differences in Health Studies of the prevalence of symptoms during deployment in the POW revealed few differences between women and men of the First Cavalry Division. Men reporting to sick call were,more likely to be diagnosed with orthopedic and dermatologic disorders, and women were more likely to be diagnosed with psychiatric and optometric disorders (Hines, 1993~. In a cluster study after the occurrence of unexplained illnesses among POW veterans in Indiana, DeFraites et al. (1992) found that the prevalence of symptoms among men and women reserve troops was similar. Wolfe has reported preliminary results suggesting thnt Acme PTSD symptomatology is significantly associated with a range of self- reported symptoms in women (Wolfe et al., 1994~. Studies of gender differences in PTSD and other symptoms indicate that prior abuse, coupled with exposure to combat stress, may affect women and men differently. The need for prospective longitudinal studies of both women and men was reinforced by results of a study of PTSD symptoms and precombat sexual and physical abuse among Desert Storm veterans who attended a mental health clinic (297 veterans, including 28 women). Women veterans who reported previous abuse had higher Mississippi Scale scores, higher combat- related PTSD and nonspecific PTSD scores, and higher depression scores than those who had not been abused. Precombat-abused male veterans did not differ from the nonabused in PTSD symptoms (Engel et al., 19939. Still another study of reserve troops found no overall gender differences in PTSD indicators (Mississippi PTSD Scale, Beck Depression Inventory, and SCL-90-R) for noncombat reservists, but gender differences did appear for two specific combat units. The first unit had experienced fatalities and injuries Tom a SCUD missile attack and the second had morale problems. Thus, data to support gender differences were found only in units in which there had been combat-related trauma or impaired morale (Perconte et al., 1993~. Some investigators have found evidence of anticipatory anxiety about mobilization among Vietnam veteran women who subsequently were diagnosed with PTSD. A small sample of Army reserve nurses who anticipated mobilization during ODS experienced higher levels of anxiety than similar civilian registered nurses. Separation from loved ones and financial concerns were the greatest contributors to anxiety. Detailed and consistent information from army commands reduced anxiety (Wynd and Dziedzicki, 19929. In

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114 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR another study, women who had had PTSD linked to Vietnam service experienced intensification of their distress during ODS regardless of whether they were deployed (Wolfe et al., 1992a). Aside from these reports, few have examined gender differences in health related to the war. The few reports to date have focused on the development of symptoms and PTSD. In a study of reservists (653 POW veterans and 259 stateside duty troops), Sutker et al. (1995a) examined the hypothesis that ethnic minority status and female gender were associated with greater psychological distress after war zone duty. All troops were studied within 1 year of return from the Gulf. Women reported more physical or somatic symptoms, including more headaches, lack of energy, cold or flu symptoms, and upset stomach, than men regardless of their deployment status. There were no statistically significant gender differences in depression, anxiety, or anger. Minority men reported more PTSD symptoms than white men. The small numbers of minority women in this study may have limited the ability to detect interactive effects of gender and ethnicity. Studies examining correlates of symptoms have identified combat stress, sexual harassment and assault, leadership and unit morale, and family care worries as important. One study of women and men immediately after their return from the Gulf demonstrated that both women and men experienced war zone stress related to combat exposure. No significant gender differences in the Lauder combat scores (describing the kinds of combat stressors to which people were exposed) were found, although men's scores were somewhat higher. Results of the more comprehensive ODS expanded checklist found that the three most commonly reported war zone stressors for both genders were formal alert for chemical or biological warfare, receiving incoming fire from large arms, and witnessing death and disfigurement of enemy troops. PTSD scores were higher for women (9% of women and 4% of men scored above 89 on the Mississippi Scale). Women reported more PTSD symptoms and had higher BSI scores than men. These findings suggest that women were more symptomatic during the initial postdeployment phase. Wolfe et al. (1993) suggest that this difference may be attributable to women's socialization; women's reporting symptoms more freely than men; family-related reentry stressors; prior stress, such as sexual or criminal victimization, leaving residual symptoms and greater sensitivity to new stress; and sexual harassment or assault experienced during deployment. Women with PTSD also reported more physical symptoms than men (Wolfe et al., 1995~. This finding suggests that some but not all of the physical symptomatology reported by POW women vets may be related to PTSD. Wolfe et al. (1995) found that both men and women reservists reported negative change in physical and psychological health since they returned from the PG and that more women than men reported a change for the worse in both physical and psychological health. More women had evidence of presumptive

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HEALTH OUTCOMES 115 PTSD and reported health symptoms in conjunction with PTSD. Headaches, lack of energy, aches or pains, nervousness, tension, insomnia, and depression were endorsed more frequently by women than by men. Gender differences in needs for support on return home have received little attention, yet it is reasonable to believe that stresses related to separation from home and family affected women and men in different ways. According to preliminary findings by Pierce (1995) among 525 Air Force women who were activated, being a parent was associated with more health problems and depressive symptoms, and this effect was pronounced for women who were deployed in the theater. Nelson et al. (1996) conducted ethnographic research regarding family support needs associated with mobilization of the National Guard and reserve forces by interviewing 59 military members, family members (including children), commanders, and family support personnel from National Guard and reserve forces; by using participant observation in selected units; and by examining cultural artifacts such as documents, journals, and newspapers. This research involved interviewing in great detail this nonrandomly selected small group of individuals in a very open-ended fashion. Nelson found that staying connected in an uncertain environment was a universal concern that was exacerbated when units were fragmented. Living with the war was unusual for families who "watched" the war on television as if it were a staged theatrical production. Indeed, military members recounted watching themselves being attacked on television as the attack was occurring and they were putting on protective gear. Fluctuating emotions were common throughout families. Refocusing lives became the major task for the families of those who returned from the Gulf. Family support systems were regarded as helpful but not easily accessed. Moreover, the study revealed a need to train families better to cope with deployment, to improve information transmission, and to support reassimilation after the war. In particular, children needed preparation as did their caretakers. Financial issues were among some of the most difficult for families to resolve (because of the delay in receiving military pay, some families could not buy food). Nelson has indicated that although returning from the Gulf represented a vulnerable period, it also was an opportune time for helping families. Deployed women whose family issues were well managed may have had reduced anxiety or stress during deployment and reduced familial stress on return from deployment. Further emphasis by commanders of such leadership or management issues for both women and men in combat situations may alleviate some of the problems experienced in-theater and after deployment.

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116 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR Health Issues Related to Men and Women Serving Together in Combat Situations In addition to assessing gender differences in health outcomes and exposures, researchers have begun to address the consequences of women and men serving together in combat. Most American military women and men carried themselves through the conflict without major problems, but it remains important to improve the training of both men and women on active duty and in the reserves or National Guard in handling these sensitive issues. As discussed earlier in this chapter, Wolfe and colleagues have begun to describe women's exposures to stressors such as physical or sexual harassment and assault during deployment. Also, Engel et al. (1993) found that precombat abuse led to higher rates of PTSD symptoms in female POW veterans and that deployed women with a prior history of abuse had greater PTSD symptomatology than those without a history of abuse. The long-term consequences of abuse prior to deployment, coupled with harassment, discrimination, and abuse during deployment and demobilization, merit further study. Sexual activity between women and men may eventuate in pregnancy and sexually transmitted disease, both preventable with access to appropriate preventive measures. Another committee of the IOM (IOM, l995b) recently reported on research needs related to the health effects of military service on women.