Association of deployment characteristics and exposures with persistent ill health among 1990-1991 Gulf War veterans in the VA Million Veteran Program.

BACKGROUND: Veterans of the 1990-1991 Gulf War have experienced excess health problems, most prominently the multisymptom condition Gulf War illness (GWI). The Department of Veterans Affairs (VA) Cooperative Studies Program #2006 "Genomics of Gulf War Illness in Veterans" project was established to address important questions concerning pathobiological and genetic aspects of GWI. The current study evaluated patterns of chronic ill health/GWI in the VA Million Veteran Program (MVP) Gulf War veteran cohort in relation to wartime exposures and key features of deployment, 27-30 years after Gulf War service. METHODS: MVP participants who served in the 1990-1991 Gulf War completed the MVP Gulf War Era Survey in 2018-2020. Survey responses provided detailed information on veterans' health, Gulf War exposures, and deployment time periods and locations. Analyses determined associations of three defined GWI/ill health outcomes with Gulf War deployment characteristics and exposures. RESULTS: The final cohort included 14,103 veterans; demographic and military characteristics of the sample were similar to the full population of U.S. 1990-1991 Gulf War veterans. Overall, a substantial number of veterans experienced chronic ill health, as indicated by three defined outcomes: 49% reported their health as fair or poor, 31% met Centers for Disease Control and Prevention criteria for severe GWI, and 20% had been diagnosed with GWI by a healthcare provider. Health outcomes varied consistently with veterans' demographic and military characteristics, and with exposures during deployment. All outcomes were most prevalent among youngest veterans (< 50 years), Army and Marine Corps veterans, enlisted personnel (vs. officers), veterans located in Iraq and/or Kuwait for at least 7 days, and veterans who remained in theater from January/February 1991 through the summer of 1991. In multivariable models, GWI/ill health was most strongly associated with three exposures: chemical/biological warfare agents, taking pyridostigmine bromide pills, and use of skin pesticides. CONCLUSIONS: Results from this large cohort indicate that GWI/chronic ill health continues to affect a large proportion of Gulf War veterans in patterns associated with 1990-1991 Gulf War deployment and exposures. Findings establish a foundation for comprehensive evaluation of genetic factors and deployment exposures in relation to GWI risk and pathobiology.

Linked Exposures Across Databases: an exposure common data elements aggregation framework to facilitate clinical exposure review.

Understanding the health outcomes of military exposures is of critical importance for Veterans, their health care team, and national leaders. Approximately 43% of Veterans report military exposure concerns to their VA providers. Understanding the causal influences of environmental exposures on health is a complex exposure science task and often requires interpreting multiple data sources; particularly when exposure pathways and multi-exposure interactions are ill-defined, as is the case for complex and emerging military service exposures. Thus, there is a need to standardize clinically meaningful exposure metrics from different data sources to guide clinicians and researchers with a consistent model for investigating and communicating exposure risk profiles. The Linked Exposures Across Databases (LEAD) framework provides a unifying model for characterizing exposures from different exposure databases with a focus on providing clinically relevant exposure metrics. Application of LEAD is demonstrated through comparison of different military exposure data sources: Veteran Military Occupational and Environmental Exposure Assessment Tool (VMOAT), Individual Longitudinal Exposure Record (ILER) database, and a military incident report database, the Explosive Ordnance Disposal Information Management System (EODIMS). This cohesive method for evaluating military exposures leverages established information with new sources of data and has the potential to influence how military exposure data is integrated into exposure health care and investigational models.

International perspective on military exposure data sources, applications, and opportunities for collaboration.

Military personnel may be exposed to a range of hazards. The assessment, documentation and reporting of military exposure information are important steps to guide health protection, services, and research to support actively serving members and veterans. In 2021, a Working Group of researchers from veteran and defense administrations across the Five Eyes countries (Australia, Canada, New Zealand, the United Kingdom, and the United States) was established to examine large military exposure data sources available in each country, their applications, and opportunities to leverage information across administrations and internationally. We provide a brief summary of this work here to highlight some successful examples of data applications and to elicit interest in this evolving area of exposure science.

Incidence and risk factors for postpartum mood and anxiety disorders among women veterans.

BACKGROUND: Our aim was to determine rates of postpartum mood and anxiety disorders (PMADs) among U.S. women Veterans and the overlap among PMADs. We further sought to identify PMAD risk factors, including those unique to military service. METHODS: A national sample of women Veterans completed a computer-assisted telephone interview (N = 1414). Eligible participants were aged 20-45 and had separated from service within the last 10 years. Self-report measures included demographics, general health, reproductive health, military exposures, sexual assault, childhood trauma, and posttraumatic stress disorder (PTSD). The PMADs of interest were postpartum depression (PPD), postpartum anxiety (PPA) and postpartum PTSD (PPPTSD). This analysis included 1039 women Veterans who had ever been pregnant and who answered questions about PPMDs related to their most recent pregnancy. RESULTS: A third (340/1039, 32.7%) of participants were diagnosed with at least one PMAD and one-fifth (215/1039, 20.7%) with two or more. Risk factors common for developing a PMAD included: a mental health diagnosis prior to pregnancy, a self-report of ever having had a traumatic birth experience, and most recent pregnancy occurring during military service. Additional risk factors were found for PPD and PPPTSD. CONCLUSION: Women Veterans may be at an increased risk for developing PMADs due to high rates of lifetime sexual assault, mental health disorders, and military-specific factors including giving birth during military service and military combat deployment exposures.

Gulf War Illness Clinical Trials and Interventions Consortium (GWICTIC): A collaborative research infrastructure for intervention and implementation.

AIMS: There is an inadequate portfolio of treatments for Gulf War Illness (GWI), a complex disease involving multiple organ systems, and early-phase clinical trials are hampered by many logistical problems. To address these challenges, the Gulf War Illness Clinical Trials and Interventions Consortium (GWICTIC) was formed with the aims of (i) creating a collaborative consortium of clinical and scientific researchers that will rapidly implement rigorous and innovative phase I and II clinical trials for GWI, (ii) perform at least four phase I or II clinical trials, (iii) provide a foundation of scalable infrastructure and management in support of the efficient and successful operation of the GWICTIC, and (iv) partner with the Boston Biorepository, Recruitment & Integrated Network for GWI and other GWI investigators to develop a common data element platform for core assessments and outcomes. MAIN METHODS: The GWICTIC brings together a multidisciplinary team of researchers at several institutions to provide scientific innovation, statistical and computational rigor, and logistical efficiency in the development and implementation of early-phase low-risk clinical trials for GWI. The GWICTIC core trials adhere to a Veteran-centered philosophy and focus on interventions with multiple mechanistic targets to maximize the likelihood of efficacy. To support rapid and efficient study startup and implementation across the GWI research community, the GWICTIC will share infrastructure with investigator-initiated research studies funded under separate mechanisms. SIGNIFICANCE: The GWICTIC will leverage the efficiencies of centralized research support and innovative trial designs to address several longstanding needs in the GWI interventions research community.

Slow Burns: A Qualitative Study of Burn Pit and Toxic Exposures Among Military Veterans Serving in Afghanistan, Iraq and Throughout the Middle East.

During deployment to the Persian Gulf War and Southwest Asia theatre of operations, Veterans often experienced various hazards, foremost being open-air burn pits and oil well fires. While over 23 presumptive conditions (ranging from brain cancer, interstitial lung disease, and lymphomas to sleep/mood disorders, depression, and cognitive impairment) have been studied in connection with their military-related exposures, there is a paucity of qualitative research on this topic. This is especially true in the context of explanatory models and health belief systems, vis-à-vis underlying social and cultural factors. The current paper provides a balanced conceptual framework (summarizing causal virtues and shortcomings) about the challenges that Veterans encounter when seeking medical care, screening assessments and subsequent treatments.

Brain-Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of 1990-1991 Gulf War Veterans in the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study.

The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990-1991 Gulf War. The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S. sites that included clinical assessments, brain imaging, neuropsychological testing, and analyses of a broad range of immune and immunogenetic parameters. GWI cases were similar to controls on most demographic, military, and deployment characteristics although on average were two years younger, with a higher proportion of enlisted personnel vs. officers. Results of physical evaluation and routine clinical lab tests were largely normal, with few differences between GWI cases and healthy controls. However, veterans with GWI scored significantly worse than controls on standardized assessments of general health, pain, fatigue, and sleep quality and had higher rates of diagnosed conditions that included hypertension, respiratory and sinus conditions, gastrointestinal conditions, and current or lifetime depression and post-traumatic stress disorder. Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009). Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI. Data and samples from the GWIC project are now stored in a repository for use by GWI researchers. Future reports will present detailed findings on brain structure and function, immune function, and association of neuroimmune measures with characteristics of GWI and Gulf War service.