Objectives: To examine whether severe Gulf War illness (SGWI) case status was associated with longitudinal multimorbidity patterns. Methods: Participants were users of the Veteran Health Administration Health Care System drawn from the Gulf War Era Cohort and Biorepository (n = 840). Longitudinal measures of multimorbidity were constructed using (1) electronic health records (Charlson Comorbidity Index; Elixhauser; and Veterans Affairs Frailty Index) from 10/1/1999 to 6/30/2023 and (2) self-reported medical conditions (Deficit Accumulation Index) since the war until the survey date. Accelerated failure time models examined SGWI case status as a predictor of time until threshold level of multimorbidity was reached, adjusted for age and sociodemographic and military characteristics. Results: Models, adjusted for covariates, revealed that (1) relative to the SWGI- group, the SGWI+ group was associated with an accelerated time for reaching each threshold and (2) the relationship between SGWI and each threshold was not moderated by age. Discussion: Findings suggest that veterans with SGWI experienced accelerated aging.

Abstract Purpose: The Veterans Health Administration (VA) created National TeleOncology (NTO) service in 2019 to provide telehealth cancer care to Veterans and to augment care provided at VA facilities through a hub and spoke model. More recently, VA established a Decentralized Clinical Trials (DCTs) infrastructure to support clinical trials (CTs) that rely on telehealth, where research staff are at different locations, and/or where a single IRB provides oversight even when subjects are at different locations. Brief Description: Research support and infrastructure is variable across VA facilities resulting in uneven access to cancer CTs in the VA system. Veterans often live in rural areas or have transportation challenges, which are barriers to participate in CTs. The COVID-19 pandemic resulted in increased telehealth use in clinical care and in CTs, providing the rationale for a focused effort in DCTs. DCTs have the potential to reduce barriers to CT involvement at the facility- and patient-level and may be more representative of real-world clinical scenarios. Summary of Data: Since its inception, NTO has provided hematology and oncology telehealth care to over 10,000 Veterans, of which 47.5% live in rural or highly rural areas, 76.5% are white and 13.2% are black or African American. Because the NTO program provides clinical care via telehealth modalities, patients who receive care through NTO may be more comfortable with participating in CTs that use telehealth, and thus are part of a pool of potentially eligible subjects.Since creation of the DCT program, three cancer DCTs have been conducted in the VA (1) BNT001 Digital Therapeutic Feasibility Pilot Study, (2) Cemiplimab Survivorship Epidemiology (CASE) Study, and (3) Proof-Of-ConcepT DEcentralized CliNical TrIAL (POTENTIAL) study. The BNT study enrolled 24 Veterans, 19 were male, 22 were white, 13 lived in rural areas, and the median age at enrollment was 68 years, including numerous cancer diagnoses. Veterans enrolled in the BNT study received cancer care at seven VA facilities. The CASE study has enrolled 24 male Veterans, 23 were white, 5 lived in rural areas, and the median age at enrollment was 74 years. The POTENTIAL study enrolled 4 male Veterans, 3 were white, 2 lived in rural areas, and the median age at enrollment was 72 years. Upcoming DCTs will focus on the following disease types: metastatic non-small cell lung cancer, multiple myeloma, and relapsed/refractory diffuse large B-cell lymphoma. Conclusions: The VA provides clinical cancer care to Veterans through the NTO program. The DCT program builds upon the existing clinical infrastructure to conduct CTs on a national scale. The NOP DCT team is a component of the VA’s Enhance Equity and Access to Clinical Trials (ENACT) initiative, which is part of Cancer Moonshot. The DCT program intends to expand CT opportunities to Veterans with cancer, minimize barriers to CT activation and enrollment, and improve access to cancer CTs for all Veterans. Citation Format: Ashlyn Press, Jennifer Ordman, Jacqueline Boreland, Zachary Burningham, Shelby Schoenborn, Tiffany Stewart, Bethany Oberg, Perri Pepperman, Holly Morris, Sarah Bloemers, Nawshin Kutub, Shannon Elam, Michael J. Kelley, Daphne Friedman. Veterans Health Administration: Decentralized clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 919.

Gulf War illness (GWI) is a chronic multisymptom disorder of unknown etiology that is believed to be caused by neurotoxicant exposure experienced during deployment to the Gulf War. Posttraumatic stress disorder (PTSD) covaries with GWI and is believed to play a role in GWI symptoms. The present study examined the association between self-reported military exposures and GWI, stratified by PTSD status, in veterans from the Gulf War Era Cohort and Biorepository who were deployed to the Persian Gulf during the war. Participants self-reported current GWI and PTSD symptoms as well as military exposures (e.g., pyridostigmine [PB] pills, pesticides/insecticides, combat, chemical attacks, and oil well fires) experienced during the Gulf War. Deployed veterans' (N = 921) GWI status was ascertained using the Centers for Disease Control and Prevention definition. Individuals who met the GWI criteria were stratified by PTSD status, yielding three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression, adjusted for covariates, was used to examine associations between GWI/PTSD groups and military exposures. Apart from insect bait use, the GWI+/PTSD+ group had higher odds of reporting military exposures than the GWI+/PTSD- group, adjusted odds ratio (aOR) = 2.15, 95% CI [1.30, 3.56]-aOR = 6.91, 95% CI [3.39, 14.08]. Except for PB pills, the GWI+/PTSD- group had a higher likelihood of reporting military exposures than the GWI- group, aOR = 2.03, 95% CI [1.26, 3.26]-aOR = 4.01, 95% CI [1.57, 10.25]. These findings are consistent with roles for both PTSD and military exposures in the etiology of GWI.

BackgroundUntil recently, multi-agent chemotherapy (CT) was the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Clinical trials have confirmed benefits in overall survival (OS) and progression-free survival with immunotherapy (IO) compared to CT. This study compares real-world treatment patterns and outcomes between CT and IO administrations in second-line (2L) settings for patients with stage IV NSCLC. Materials and methodsThis retrospective study included patients in the United States Department of Veterans Affairs healthcare system diagnosed with stage IV NSCLC during 2012-2017 and receiving IO or CT in the 2L. Patient demographics and clinical characteristics, healthcare resource utilization (HCRU), and adverse events (AEs) were compared between treatment groups. Logistic regression was used to examine differences in baseline characteristics between groups, and inverse probability weighting multivariable Cox proportional hazard regression was used to analyze OS. ResultsAmong 4,609 Veterans who received first-line (1L) therapy for stage IV NSCLC, 96% received 1L CT alone. A total of 1,630 (35%) were administered 2L systemic therapy, with 695 (43%) receiving IO and 935 (57%) receiving CT. Median age was 67 years (IO group) and 65 years (CT group); most patients were male (97%) and white (76-77%). Patients administered 2L IO had a higher Charlson Comorbidity Index than those administered CT (p = 0.0002). 2L IO was associated with significantly longer OS compared with CT (hazard ratio 0.84, 95% CI 0.75-0.94). IO was more frequently prescribed during the study period (p < 0.0001). No difference in rate of hospitalizations was observed between the two groups. ConclusionsOverall, the proportion of advanced NSCLC patients receiving 2L systemic therapy is low. Among patients treated with 1L CT and without IO contraindications, 2L IO should be considered, as this supports potential benefit of IO for advanced NSCLC. The increasing availability and indications for IO will likely increase the administration of 2L therapy to NSCLC patients.

Federal agencies, including the Department of Veterans Affairs (VA), have prioritized improved access to scientific data and results collected through federally funded research. Our VA Cooperative Studies Program Epidemiology Center in Durham, North Carolina (CSPEC-Durham) assembled a repository of data and specimens collected through multiple studies on Veteran health issues to facilitate future research in these areas. We developed a single protocol, request process that includes scientific and ethical review of all applications, and a database architecture using metadata (common variable descriptors) to securely store and share data across diverse studies. In addition, we created a mechanism to allow data and specimens collected through older studies in which re-use was not addressed in the study protocol or consent forms to be shared if the future research is within the scope of the original consent. Our CSPEC-Durham Data and Specimen Repository currently includes research data, genomic data, and study specimens (e.g., DNA, blood) for three content areas: colorectal cancer, amyotrophic lateral sclerosis, and Gulf War research. The linking of the study specimens and research data can support additional genetic analyses and related research to improve Veterans' health.

AimsGulf War Illness (GWI) is a chronic multisymptom illness with debated etiology and pathophysiology. This systematic review catalogues studies of validated biological tests for diagnosing GWI and of associations between biological measures and GWI for their promise as biomarkers.Main methodsWe searched multiple sources through February 2020 for studies of diagnostic tests of GWI and of associations between biological measures and GWI. We abstracted data on study design, demographics, and outcomes. We assessed the risk of bias of included studies.Key findingsWe did not identify any studies validating tests of biomarkers that distinguish cases of GWI from non-cases. We included the best-fitting studies, 32 completed and 24 ongoing or unpublished studies, of associations between GWI and biological measures. The less well-fitting studies (n = 77) were included in a Supplementary Table. Most studies were of the central nervous and immune systems and indicated a significant association of the biological measure with GWI case status. Biological measures were heterogeneous across studies.SignificanceOur review indicates that there are no existing validated biological tests to determine GWI case status. Many studies have assessed the potential association between a variety of biological measures and GWI, the majority of which pertain to the immune and central nervous systems. More importantly, while most studies indicated a significant association between biological measures and GWI case status, the biological measures across studies were extremely heterogeneous. Due to the heterogeneity, the focus of the review is to map out what has been examined, rather than synthesize information.

e19295 Background: Immunotherapy (IO) has revolutionized the treatment paradigm for patients with advanced non-small cell lung cancer (NSCLC). Study objectives were to evaluate utilization of IO as first-line (1L) therapy and compare clinical characteristics between patients receiving IO and those receiving CT in 1L setting. Methods: Using the U.S. Department of Veterans Affairs corporate data warehouse, patients with stage IV NSCLC diagnosed 2012-2017 and initiated non-targeted systemic therapy within 120 days of diagnosis were selected. Unadjusted descriptive statistics were used to compare patient characteristics, inpatient and outpatient clinic visits, and prevalence of select adverse events (AE) between patients receiving IO monotherapy and CT. Kaplan-Meier and Cox regression approaches with and without propensity score matching (PSM) were used for overall survival (OS) analyses. OS was calculated from treatment initiation date to death or end of study period in June 2019. Results: 4609 patients were included in the analysis: 3.4% (n = 156) received IO monotherapy, 96% (n = 4426) received CT, and 0.6% (n = 27) received IO+CT (IO+CT not included in analysis). IO patients were older than CT patients (median age 69 vs. 66 years, p < 0.0001) and more frequently resided in the Midwest and West regions whereas CT patients were more likely to live in the Northeast and South (p = 0.0024). There were no significant differences in IO and CT by other demographic and clinical characteristics. Estimated median OS was 7.5 months (95% CI 7.2-7.7) for CT and 7.9 months (95% CI 5.3-12.6) for IO patients. The unadjusted HR for IO compared to CT patients was 0.81 (95% CI 0.67-0.98). With 1:4 PSM (144 and 559 patients matched in the IO and CT groups, respectively), the HR was 0.75 (95% CI 0.60-0.93). The mean number of outpatient visits for IO and CT patients were 47 and 36, respectively (p = 0.003). No difference in number of hospitalizations or length of hospital stays between the two groups was observed. Common AEs in the IO group were dyspnea (58%), colitis/enterocolitis (42%), and anemia (30%). Common AEs among CT patients were colitis/enterocolitis (36%), anemia (32%), and nausea/vomiting (31%). Conclusions: In a real-world 1L setting among veterans with NSCLC, improvement in OS was observed among patients receiving IO monotherapy compared to those receiving CT, and IO patients had a greater number of outpatient visits. Continued assessment of treatment patterns and impact of IO are needed as the use of IO continues to expand.

INTRODUCTION:After the 1990 to 1991 conflict in the Persian Gulf, many Gulf War Veterans began reporting numerous unexplained symptoms including, but not limited to, systemic pain, fatigue, flu-like symptoms, and difficulty with memory/concentration. These symptom clusters are now referred to as Gulf War Illness (GWI). Although the etiology of GWI is still debated, as many as 250,000 former service members have been continually suffering from GWI since 1991, making the need for treatment urgent. A broad variety of treatments have been considered for GWI, but there has not been a broad and comprehensive assessment of what is known and not known about GWI treatment. We conducted a systematic review to catalogue the types of treatments that have been examined for GWI, to evaluate the effectiveness and harms of these interventions, and to identify promising and ongoing areas of future GWI treatment research.MATERIALS AND METHODS:We searched electronic databases, trial registries, and reference lists through September 2019 for randomized controlled trial and nonrandomized controlled trial and cohort studies directly comparing interventions for Veterans with GWI to each other, placebo, or usual care. We abstracted data on study design, demographics, interventions, and outcomes. Two reviewers independently assessed studies for inclusion, quality, and strength of evidence (SOE) using prespecified criteria. We resolved discordant ratings by discussion and consensus.RESULTS:We identified 12 randomized controlled trials, each of which examined a different intervention for GWI. We found moderate SOE that cognitive behavioral therapy and exercise, separately and in combination, were associated with improvements in several GWI symptom domains. There was low SOE of benefit from two mindfulness-based interventions and continuous positive airway pressure (CPAP). Mindfulness-based stress reduction improved pain, cognitive functioning, fatigue, depression, and posttraumatic stress disorder (PTSD), whereas mind-body bridging improved fatigue, depression, posttraumatic stress disorder, and sleep, although pain and other outcomes did not improve. Continuous positive airway pressure improved overall physical health, pain, cognitive functioning, fatigue, mental health, and sleep quality in a small study of Veterans with sleep-disordered breathing and GWI. We found moderate SOE that doxycycline is ineffective for GWI in mycoplasma DNA-positive Veterans and increases the risk of adverse events compared with placebo. We also found 33 ongoing, single-arm pilot, or unpublished studies examining a variety of interventions.CONCLUSION:Cognitive behavioral therapy (moderate SOE), exercise (moderate SOE), and mindfulness-based interventions (low SOE) may be effective in improving several symptom domains in patients with GWI. Doxycycline was ineffective and associated with harms (moderate SOE). Larger, more rigorous studies are needed to confirm the benefits found in completed trials. A wide array of treatments are being assessed in ongoing trials. A sufficient evidence base will need to be developed to guide clinicians about which treatments are most likely to be effective in clinical practice and which treatments should be avoided.