Study Of Gulf War Veterans Research Articles

Recruiting a special sample with sparse resources: Lessons from a study of Gulf War veterans

Recruitment is the most common failure point for clinical studies, with recruitment failure adversely affecting science, dollar costs, human capital, and the ethical risk-benefit trade-off to study participants. Added problems attend recruitment of special and/or challenging candidate populations, particularly in settings of sparse recruitment resources. Obstacles to study recruitment and participation of ill Gulf War veterans (GWVs) include health barriers, work and family obligations, mistrust of the medical/scientific community, and challenges to identifying/reaching potential participants. We sought to identify and implement a minimal-cost multipronged recruitment approach for a small single-site (<50 participants) study of a special group, ill GWVs, with approaches substantially applicable to other recruitment settings and larger multisite studies. Categories of recruitment approach included directed as well as general media, collaborations with support groups/interest groups, local free advertising resources (Craigslist and Backpage), physician outreach, Internet-based approaches, and referrals from study participants and screenees. We describe the subcategories and yield of each approach within each approach. Each approach contributed candidates to the final recruitment tally, with the largest fractional contribution by directed media (52%). Among the remainder, no other individual approach was clearly dominant (largest contribution: 13%). Special population subsamples present special challenges; all approaches cited may not be useful in all settings and subpopulations. A multipronged suite of minimal-cost approaches led to successful recruitment to target for this single-site clinical trial for a special population with significant recruitment challenges. It additionally yielded a nation-wide corpus of several hundred individuals interested in participation in future studies of GWVs. While certain approaches produced disproportionate yield, it was not possible to predict these a priori. We suggest that this model, which incorporates a suite of approaches, and delineates backup approaches in the event of recruitment shortfall, may provide a template applicable to recruitment of other special samples in settings of limited resources and also is germane to cost-effective recruitment in studies more generally.

Renal Effects of Exposure to Natural and Depleted Uranium: A Review of the Epidemiologic and Experimental Data

Elevated levels of naturally occurring uranium in groundwater have been found in small geographic areas throughout the world. Relevant research was reviewed pertaining to natural and depleted uranium (DU) exposure and nephrotoxicity, including epidemiologic community-based and occupational studies, studies of Gulf War veterans exposed to DU, and experimental studies in animals. Occupational cohort studies do not provide evidence of an increased risk of kidney-related mortality among uranium-exposed workers. However, occupational and community-based studies of populations chronically exposed to elevated drinking-water concentrations of uranium provide some evidence of adverse renal effects, as assessed by biomarkers of proximal tubule damage such as urinary levels of glucose, calcium, and various low-molecular-weight proteins. Indications of proximal tubule effects, as evidenced by increased urinary β2-microglobulin and retinol binding protein levels, were also seen in the most recent follow-up surveillance study of Gulf War veterans exposed to DU. The reported β2-microglobulin levels in these studies were generally considered to be within normal limits, but the long-term implications of the observed variation in these levels are not established. The kidney was observed to be a target of uranium toxicity following oral and implantation exposure routes in several animal species. The interpretation and importance of the observed changes in biomarkers of proximal tubule function are important questions that indicate the need for additional clinical, epidemiological, and experimental research.

Familial aggregation of fainting in a case–control study of neurally mediated hypotension patients who present with unexplained chronic fatigue

We hypothesized that family history of fainting is a risk factor for adult-onset neurally mediated hypotension (NMH) in patients who present with chronic fatigue rather than fainting. A nested case-control study of Gulf War veterans gathered fainting histories directly from 197 first-degree relatives of 16 fatigued NMH cases, 26 fatigued controls, and 17 healthy controls. NMH status was determined by tilt testing. Female relatives of fatigued controls reported more fainting than female relatives of cases (P<0.01); there were no significant differences in the frequency of fainting in male relatives by case or control status, or in either gender by age at first faint or by familial relationship to the proband. The odds of NMH patients giving any family history of fainting were 0.56 (95% CI 0.15, 2.07). Recurrence risks calculated using lifetime prevalences of fainting in male military personnel of similar age to our participants were low (1.5-1.7) and did not differ by case or control status. Family history of fainting is not a risk factor for adult-onset NMH in fatigued veterans. Our findings may differ from other studies of familial aggregation in NMH because of study methods or because NMH-fatiguers may differ from NMH-fainters.

Neuropsychological Changes Following Military Service in Iraq

SINCE THE 1990-1991 PERSIAN GULF WAR, THE IDEA that the health of military personnel returning from major deployments should be monitored proactively has been established. Major studies are under way on both sides of the Atlantic on the health of personnel deployed to Iraq. The research that has emerged so far on US veterans of Operation Iraqi Freedom indicates that there have indeed been many psychiatric casualties, with high prevalence rates of symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety. Up to 20% of soldiers and marines returning from deployment to Iraq and Afghanistan met criteria for PTSD. Similar findings have been documented by routine screening performed by the US Army. The situation for UK personnel returning from Operation TELIC in the 2003 Iraq War is—with the exception of reservists—rather different, with a prevalence of PTSD (measured using identical measures to the US studies) and depressive symptoms similar to those of nondeployed personnel. These international differences may in part be explained by the nature of deployments, with US personnel on longer tours of duty in more dangerous parts of Iraq. It also may relate to the populations deployed—the deployed US military personnel are younger and have considerably less experience of active deployment than their British counterparts. Whatever the reasons, some of the most significant health effects for returning personnel seem to have been on mental health, and, thus far, there is no evidence of a repeat of the multiple physical symptoms that characterized Persian Gulf War illness. Most studies on military personnel have not been able to study changes in health before and after deployment. The nature of military operations means that making prior ratings of health is logistically difficult. The study by Vasterling and colleagues in this issue of JAMA is a noteworthy exception. The authors measured neuropsychological function in a cohort of military personnel prior to and following deployment to Operation Iraqi Freedom, and compared these findings with those of a cohort of nondeployed soldiers. The authors report that significant neurocognitive changes occurred after deployment, with a worsening of performance on tasks requiring sustained attention, verbal learning, and visual-spatial memory but an improvement in reaction time. Vasterling et al conclude that these results are not explained by the most likely possibilities: head injury, PTSD, and depression. One of the most consistent groups of symptoms reported following the 1991 Persian Gulf War were what might broadly be described as cognitive. Many veterans of that conflict continue to complain of difficulties in memory, word finding, concentration, and other cognitive impairments. This led to speculation that these symptoms were the result of exposure to neurotoxic agents such as organophosphate pesticides and even sarin nerve gas. As a result, a series of neuropsychological studies of Gulf War veterans was undertaken some considerable time after deployment. A review of the results of these studies did not find a consistent pattern of significant deficits, and although certain subgroups (those who reported multiple symptoms and those who selfreported greater exposure to pesticides) had more deficits, again, there was no consistent pattern. Instead, the authors of the review concluded that these deficits were only mild and that “performance on objective tasks of neuropsychological function showed little correspondence to subjective perceptions of cognitive functioning.” Nevertheless, the rationale for the present study by Vasterling et al was to use neuropsychological testing as a means of assessing possible neural dysfunction, but this time to do so before so many years had elapsed. This study is the first of its kind to follow and reassess representative samples of deployed personnel 2 to 3 months following their return home from war. Whether veterans should be concerned about the findings of Vasterling et al depends on the answers to several other questions. First, are the reported effects clinically significant? The authors emphasize that the neuropsychological changes are “mild” and “subtle.” Although data on the dis-

The impact of the 1991 Gulf War on the mind and brain: findings from neuropsychological and neuroimaging research.

Many veterans of the 1991 Gulf War (GW) have complained of somatic and cognitive symptoms that may be neurological in nature. However, whether or not changes in brain function are associated with GW service continues to be debated. Studies of GW veterans using objective, performance-based neuropsychological measures have yielded inconsistent findings, with those indicating deficits among GW veterans typically revealing only relatively mild levels of neuropsychological impairment. Further, performances on objective neuropsychological tasks show little correspondence to subjective perceptions of cognitive functioning. Although preliminary magnetic resonance spectroscopy (MRS) studies demonstrate reduced N-acetylaspartate-to-creatine (NAA/Cr) ratio in select brain regions among GW veterans who report health concerns, this work requires further replication with larger, more representative samples. There is no evidence from neuroimaging studies of a non-specific effect of GW service or of changes in brain structure or function related to health status when conventional radiological methods are used. Owing to the paucity of objective exposure, baseline health data, and the now significant time elapsed since the GW, aetiological issues may never be fully resolved. Therefore, research addressing clinical management of GW veterans with neuropsychological dysfunction and neuroimaging abnormalities may prove more fruitful than exclusive focus on aetiology.

The challenges of exposure assessment in health studies of Gulf War veterans

A variety of exposures have been investigated in Gulf War veterans' health studies. These have most commonly been by self-report in a postal questionnaire but modelling and bio-monitoring have also been employed. Exposure assessment is difficult to do well in studies of any workplace environment. It is made more difficult in Gulf War studies where there are a number and variety of possible exposures, no agreed metrics for individual exposures and few contemporary records associating the exposure with an individual. In some studies, the exposure assessment was carried out some years after the war and in the context of media interest. Several studies have examined different ways to test the accuracy of exposure reporting in Gulf War cohorts. There is some evidence from Gulf War studies that self-reported exposures were subject to recall bias but it is difficult to assess the extent. Occupational exposure-assessment methodology can provide insights into the exposure-assessment process and how to do it well. This is discussed in the context of the Gulf War studies. Alternative exposure-assessment methodologies are presented, although these may not be suitable for widespread use in veteran studies. Due to the poor quality of and accessibility of objective military exposure records, self-assessed exposure questionnaires are likely to remain the main instrument for assessing the exposure for a large number of veterans. If this is to be the case, then validation methods with more objective methods need to be included in future study designs.

The health of Australian veterans of the 1991 Gulf War: factor analysis of self-reported symptoms

Background: A recent report showed that Australian veterans of the 1991 Gulf War displayed a greater prevalence of a multitude of self-reported symptoms than a randomly sampled comparison group of...

Dichotomous factor analysis of symptoms reported by UK and US veterans of the 1991 Gulf War.

BackgroundFactor analysis is one of the most used statistical techniques to analyze the inter-relationships among symptoms reported by Gulf War veterans. The objective of this study was to apply factor analyses to binary symptom data from the UK study of Gulf War illness and the US Air Force study of Gulf War veterans, and to compare the symptom domains derived from the distinct samples.MethodsUK veterans of the 1991 Gulf War (n = 3,454), individuals deployed to Bosnia on U.N. peacekeeping operations (n = 1,979) and Gulf War-era servicemen (n = 2,577) who were not deployed to the Gulf were surveyed in 1997–1998, and US 1991 Gulf War veterans from four Air Force units (n = 1,163) were surveyed in 1995 to collect health characteristics including symptoms. Each sample was randomly split in half for exploratory and confirmatory dichotomous factor analyses with promax oblique rotation.ResultsFour correlated factors were identified in each of the samples. Three factors (Respiratory, Mood-Cognition, Peripheral Nervous) overlapped considerably across the UK cohorts. The Gastrointestinal/Urogenital factor in the UK Gulf cohort was noticeably different from the Gastrointestinal factor identified from the Bosnia and Era cohorts. Symptoms from Gulf War UK and U.S cohorts yielded similar Gastrointestinal, Respiratory and Mood-Cognition factors, despite differences in symptom inventories between the two surveys. A Musculoskeletal factor was only elicited from the US Gulf sample.ConclusionFindings of this report are consistent with those from other factor analysis studies that identified similar symptom dimensions between Gulf and non-Gulf War veterans, except that the Gastrointestinal factor in Gulf veterans included other symptom types. Correlations among factors raise the question as to whether there is a general illness, even if not unique to Gulf veterans, representing the common pathway underlying the identified factors. Hierarchical factor analysis models may be useful to address this issue.

Odors and sounds as triggers for medically unexplained symptoms: a fixed-occasion diary study of Gulf War veterans.

Both laboratory studies on healthy volunteers and epidemiological evidence from patient samples indicate that odor can act as a trigger for the reporting of medically unexplained symptoms (MUSs). The relationship between concurrent experiences of odor and MUSs has not been explored in a patient sample. This study used an 8-day fixed-occasion diary study, in which 17 veterans of the Persian Gulf War completed diary assessments of (a) the intensity and duration of odor and sound and (b) MUS severity. The results showed that the intensity of odor was positively associated with the severity on the same day and subsequent days' symptoms, whereas the duration of odor was negatively related to the severity of MUS reporting on the same day. These results are consistent with an associative mechanism underlying symptom reporting in veterans. By contrast, the duration, but not the intensity, of sound was related to the severity of MUS reporting on the same day.

Chemical Warfare and the Gulf War: A Review of the Impact on Gulf Veterans' Health

It is unlikely that Gulf War veterans are suffering chronic effects from illnesses caused by chemical warfare nerve agent exposure. Extensive investigation and review by several expert panels have determined that no evidence exists that chemical warfare nerve agents were used during the Gulf War. At no time before, during, or after the war was there confirmation of symptoms among anyone, military or civilian, caused by chemical warfare nerve agent exposure. However, studies of Gulf War veterans have found belief that chemical weapons were used, significantly associated with both severe and mild-moderate illnesses. The psychological impact of a chemical warfare attack, either actual or perceived, can result in immediate and long-term health consequences. The deployment or war-related health impact from life-threatening experiences of the Gulf War, including the perceived exposure to chemical warfare agents, should be considered as an important cause of morbidity among Gulf War veterans.

Psychiatric disorder in veterans of the Persian Gulf War of 1991

Veterans of the Persian Gulf War of 1991 have reported symptoms attributed to their military service. To review all studies comparing the prevalence of psychiatric disorders in Gulf War veterans and in a comparison group of service personnel not deployed to the Gulf War. Studies of military personnel deployed to the Gulf published between 1990 and 2001 were identified from electronic databases. Reference lists and websites were searched and key researchers were contacted for information. A total of 2296 abstracts and 409 complete articles were reviewed and data were extracted independently by two members of the research team. The prevalence of psychiatric disorder in 20 studies of Gulf War veterans was compared with the prevalence in the comparison group. Prevalence of post-traumatic stress disorder (PTSD) and common mental disorder were higher in the Gulf War veterans. Heterogeneity between studies was significant, but all reported this increased prevalence. Veterans of the Persian Gulf War reported an increased prevalence of PTSD and common mental disorder compared with other active service personnel not deployed to the Gulf. These findings are attributable to the increase in psychologically traumatic events in wartime.

Chronic fatigue in a population-based study of Gulf War veterans.

Fatigue has been associated with illness in veterans of the Gulf War; however, few studies have confirmed self-reported fatigue by using clinical evaluation, and symptomatic veterans have not been evaluated with established criteria for Chronic Fatigue Syndrome (CFS). The authors describe the frequency and clinical characteristics of CFS in a sample of veterans residing in the northwestern United States. The sample was selected randomly from U.S. Department of Defense databases of troops deployed to southwest Asia during the Gulf War. The selected individuals were invited to participate in a clinical case-control study of unexplained illness. Of 799 survey respondents eligible for clinical evaluation, 178 had fatigue symptoms. Of the 130 veterans who were evaluated clinically, 103 had unexplained fatigue, and 44 veterans met the 1994 U.S. Centers for Disease Control criteria for CFS. In this population, the authors estimated a minimum prevalence of any unexplained fatigue to be 5.1%, and of CFS to be 2.2%. The estimated prevalence was greater among females than among males. Cases were similar to healthy controls, as determined by laboratory tests and physical findings. In comparison to several clinical studies of CFS patients, the authors of this study found a lower proportion of veterans who reported a sudden onset of symptoms (19%) vs. a gradual onset (50%). Although it has previously been suggested that veterans of the Gulf War suffer from higher rates of chronic fatigue than the general population, the study results described herein--on the basis of clinical examination of a population-based sample of veterans-actually indicate that an increased rate may indeed exist. Gulf War veterans with unexplained fatigue should be encouraged to seek treatment so that the impact of these symptoms on overall quality of life can be reduced.

Pregnancy Outcomes Among U.S. Gulf War Veterans: A Population-Based Survey of 30,000 Veterans

Anecdotal reports by veterans of the Persian Gulf War of 1990 have included concern over negative reproductive outcomes, including spontaneous abortions and birth defects. Two previous birth records studies failed to findevidence of an increased risk of defects, but a large population-based study of Gulf War veterans in the United Kingdom did suggest more miscarriages than in a control population. The present health survey examined reproductive outcomes in 15,000 Gulf War veterans and a comparable number of non-Gulf War veterans. The final study group, representing a 70% rate of response to a 16-page health survey, included 11,44] Gulf War veterans and 9476 control subjects. Nearly 30% of survey participants (6043) had index pregnancies. Male Gulf veterans reported more miscarriages and stillbirths than male non-Gulf War veterans, but the difference was statistically significant only for miscarriages. Female Gulf War veterans reported the same effects, but neither was significant. Live-born infants of male Gulf War veterans reportedly had likely birth defects nearly twice as often as control infants (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.37-2.74), Female Gulf War veterans were nearly 3-fold likelier than control subjects to have a child with a likely birth defect (adjusted OR, 2.97; 95% CI, 1.47-5.99). Adjusted ORs for moderate to severe birth defects were 1.78 for males and 2.80 for females. A small excess of chromosomal defects was reported by Gulf War veterans. This large-scale population-based survey suggests that both male and female Gulf War veterans report significantly higher rates of birth defects in their live-born infants than do military control subjects. In addition, male Gulf War veterans reported significantly more miscarriages.

Self-reported exposures and their association with unexplained illness in a population-based case-control study of Gulf War veterans.

Many factors have been considered as possible causes of the unexplained illness reported by veterans of the Gulf War (GW). In this study, we report an analysis of risk factors and unexplained illness in a population-based sample of GW veterans who underwent clinical evaluation. Multiple risk factors were compared in 241 veterans who met criteria for unexplained illness and 113 healthy controls. Results suggest that GW unexplained illness is most highly associated with combat conditions, heat stress, and having sought medical attention during the GW. When controlling for multiple simultaneous exposures during the GW, interactions around pyridostigmine bromide, insecticides and repellents, and stress were not significant. These results indicate that most unexplained illness in GW veterans cannot be explained by neurotoxic effects of exposures to chemicals that inhibit cholinesterase activity.

Role of vaccinations as risk factors for ill health in veterans of the Gulf war: cross sectional study

Objectives: To explore the relation between ill health after the Gulf war and vaccines received before or during the conflict. To test the hypothesis that such ill health is limited...

Is Gulf War syndrome due to stress? The evidence reexamined.

Medical policy-makers have concluded that stress from wartime trauma and deployment constitutes an important cause of the chronic physical symptoms observed in US veterans who served in the Persian Gulf War. The author reviewed scientific articles from peer-reviewed journals referenced in the final report of the Presidential Advisory Committee on Gulf War Veterans' illnesses and conducted a MEDLINE literature search. All reported prevalence rates of post-traumatic stress disorder (PTSD) in Gulf War veterans were defined by critical cutpoints on psychometric scales constructed by summing veterans' responses on standardized symptom questionnaires rather than by clinical psychiatric interviews. Observed PTSD rates varied from 0% to 36% (mean, 9%). Correcting for measurement errors with previously determined values of the sensitivity (range 0.77 to 0.96) and specificity (range 0.62 to 0.89) of the psychometric tests yielded estimated true PTSD rates of 0% for 18 of the 20 reported rates. Mean scores on the Mississippi PTSD scale in all subgroups of Gulf War veterans were within the range of values for well-adjusted Vietnam veterans (50-89) and far below that of Vietnam veterans with psychiatrically confirmed PTSD (120-140). Most PTSD and "stress-related symptoms" reported in studies of Gulf War veterans appear to represent false-positive errors of measurement reflecting nonspecific symptoms of other conditions.

Gulf war veterans show nerve damage

A study of Gulf war veterans suffering from unexplained illness has found that some have evidence of nerve damage. Researchers from the Institute of Neurological Sciences at Glasgow's Southern General Hospital randomly selected 14 veterans from a list of those with unexplained illness and compared their responses to …

Institute of Medicine calls for coordinated studies of Gulf War veterans' health complaints

Institute of Medicine calls for coordinated studies of Gulf War veterans' health complaints

Institute of Medicine Calls for Coordinated Studies of Gulf War Veterans' Health Complaints

FEDERAL AGENCIES must redirect and coordinate data collection and research efforts, an Institute of Medicine (IOM) committee says, if answers are to be found to health questions raised by Persian Gulf War veterans (<i>JAMA</i>. 1994; 272:341). Following continued reports from some veterans that they (and sometimes their families) are inexplicably ill, apparently as a result of military service during the 1991 Desert Storm liberation of Kuwait, Congress turned late in 1993 to the Washington, DC—based IOM, a 25-year-old private, nonprofit organization providing health policy advice under the 1863 congressional charter to the National Academy of Sciences. An 18-member IOM committee now has recommended, among other things, some epidemiologic studies using a population-based survey (of those who served in southwest Asia) to learn whether, and how much, the frequency of these mystery illnesses in Persian Gulf veterans exceeds that in the civilian population. The committee also recommends a single service-connected health