The associations between injury severity, posttraumatic stress disorder (PTSD), and development of chronic diseases, such as hypertension, among military service members are not understood. We sought to (1) estimate the prevalence and incidence of PTSD within a severely injured military cohort, (2) assess the association between the presence and chronicity of PTSD and hypertension, and (3) determine whether or not initial injury severity score and PTSD are independent risk factors for hypertension. Administrative and clinical databases were used to conduct a retrospective cohort study of 3846 US military casualties injured in the Iraq and Afghanistan conflicts between February 1, 2002, and February 1, 2011. Development of PTSD and hypertension after combat injury were determined using the International Classification of Diseases, Ninth Revision codes. Multivariable competing risk regression models were used to assess associations between injury severity score, PTSD, and hypertension, while controlling for covariates. Overall prevalence of PTSD was 42.4%, and prevalence of hypertension was 14.3%. Unadjusted risk of hypertension increased significantly with chronicity of PTSD (1–15 diagnoses: hazard ratio, 1.77; 95% confidence interval, 1.46–2.14; P 15 diagnoses: hazard ratio, 2.29; 95% confidence interval, 1.85–2.84; P <0.001) compared with patients never diagnosed with PTSD. The association between injury severity score (hazard ratio, 1.06 per 5-U increment; 95% confidence interval, 1.03–1.10; P <0.001) and hypertension was significant, with little change in effect in the multivariable model (hazard ratio, 1.05 per 5-U increment; 95% confidence interval, 1.01–1.09; P =0.03). In a cohort of service members injured in combat, we found that chronicity of PTSD diagnoses and injury severity were independent risk factors for hypertension.

Importance: Traumatic brain injury (TBI) was common among US service members deployed to Iraq and Afghanistan. Although there is some evidence to suggest that TBI increases the risk of cardiovascular disease (CVD), prior reports were predominantly limited to cerebrovascular outcomes. The potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.Objective: To determine the association between TBI and subsequent CVD in post-9/11–era veterans.Design, Setting, and Participants: This was a retrospective cohort study conducted from October 1, 1999, to September 30, 2016. Participants were followed up until December 31, 2018. Included in the study were administrative data from the US Department of Veterans Affairs and the Department of Defense from the Long-term Impact of Military-Relevant Brain Injury Consortium–Chronic Effects of Neurotrauma Consortium. Participants were excluded if dates did not overlap with the study period. Data analysis was conducted between November 22, 2021, and June 28, 2022.Exposures: History of TBI as measured by diagnosis in health care records.Main Outcomes and Measures: Composite end point of CVD: coronary artery disease, stroke, peripheral artery disease, and cardiovascular death.Results: Of the 2 530 875 veterans from the consortium, after exclusions, a total of 1 559 928 veterans were included in the analysis. A total of 301 169 veterans (19.3%; median [IQR] age, 27 [23-34] years; 265 217 male participants [88.1]) with a TBI history and 1 258 759 veterans (80.7%; median [IQR] age, 29 [24-39] years; 1 012 159 male participants [80.4%]) without a TBI history were included for analysis. Participants were predominately young (1 058 054 [67.8%] <35 years at index date) and male (1 277 376 [81.9%]). Compared with participants without a history of TBI, diagnoses of mild TBI (hazard ratio [HR], 1.62; 95% CI, 1.58-1.66; P < .001), moderate to severe TBI (HR, 2.63; 95% CI, 2.51-2.76; P < .001), and penetrating TBI (HR, 4.60; 95% CI, 4.26-4.96; P < .001) were associated with CVD in adjusted models. In analyses of secondary outcomes, all severities of TBI were associated with the individual components of the composite outcome except penetrating TBI and CVD death.Conclusions and Relevance: Results of this cohort study suggest that US veterans with a TBI history were more likely to develop CVD compared with veterans without a TBI history. Given the relatively young age of the cohort, these results suggest that there may be an increased burden of CVD as these veterans age and develop other CVD risk factors. Future studies are needed to determine if the increased risk associated with TBI is modifiable.

Background: The relationship between traumatic injury and subsequent mental health diagnoses is not well understood and may have significant implications for patient screening and clinical intervention. We sought to determine the adjusted association between traumatic injury and the subsequent development of post‐traumatic stress disorder (PTSD), depression, and anxiety.Methods: Using Department of Defense and Veterans Affairs datasets between February 2002 and June 2016, we conducted a retrospective cohort study of 7,787 combat‐injured United States service members matched 1:1 to combat‐deployed, uninjured service members. The primary exposure was combat injury versus no combat injury. Outcomes were diagnoses of PTSD, depression, and anxiety, defined by International Classification of Diseases 9th and 10th Revision Clinical Modification codes.Results: Compared to noninjured service members, injured service members had higher observed incidence rates per 100 person‐years for PTSD (17.1 vs. 5.8), depression (10.4 vs. 5.7), and anxiety (9.1 vs. 4.9). After adjustment, combat‐injured patients were at increased risk of development of PTSD (HR 2.92, 95%CI 2.68–3.17), depression (HR 1.47, 95%CI 1.36–1.58), and anxiety (HR 1.34, 95%CI 1.24–1.45).Conclusions: Traumatic injury is associated with subsequent development of PTSD, depression, and anxiety. These findings highlight the importance of increased screening, prevention, and intervention in patients with exposure to physical trauma.

Background: A better understanding of the long-term health effects of combat injury is important for the management of veterans’ health in the Department of Defense (DoD) and Veterans Affairs (VA) health care systems and may have implications for primary care management of civilian trauma patients. Objective: To determine the impact of traumatic injury on the subsequent development of hypertension (HTN), diabetes mellitus (DM), and coronary artery disease (CAD) after adjustment for sociodemographic, health behavior, and mental health factors. Design: Retrospective cohort study of current and former US military personnel with data obtained from both the DoD and VA health care systems. Participants: Combat injured (n = 8727) service members between 1 February 2002 and 14 June 2016 randomly selected from the DoD Trauma Registry matched 1:1 based on year of birth, sex, and branch of service to subjects that deployed to a combat zone but were not injured. Main Measures: Traumatic injury, stratified by severity, compared with no documented injury. Diagnoses of HTN, DM, and CAD defined by International Classification of Diseases 9th or 10th Revision Clinical Modification codes. Key Results: After adjustment, severe traumatic injury was significantly associated with HTN (HR 2.78, 95% CI 2.18–3.55), DM (HR 4.45, 95% CI 2.15–9.18), and CAD (HR 4.87, 95% CI 2.11–11.25), compared with no injury. Less severe injury was associated with HTN (HR 1.14, 95% CI 1.05–1.24) and CAD (HR 1.62, 95% CI 1.11–2.37). Conclusions: Severe traumatic injury is associated with the subsequent development of HTN, DM, and CAD. These findings have profound implications for the primary care of injured service members in both the DoD/VA health systems and may be applicable to civilian trauma patients as well. Further exploration of pathophysiologic, health behavior, and mental health changes after trauma is warranted to guide future intervention strategies.

Background: Traditionally, patient risk scoring is done by evaluating vital signs and clinical severity scores with clinical intuition. Urinary biomarkers can add objectivity to these models to make risk prediction more accurate. We used metabolomics to identify prognostic urinary biomarkers of mortality or need for renal replacement therapy (RRT). Additionally, we assessed acute kidney injury (AKI) diagnosis, injury severity score (ISS), and AKI stage.Methods: Urine samples (n = 82) from a previous study of combat casualties were evaluated using proton nuclear magnetic resonance (¹H-NMR) spectroscopy. Chenomx software was used to identify and quantify urinary metabolites. Metabolite concentrations were normalized by urine output, autoscaled, and log-transformed. Partial least squares discriminant analysis (PLS-DA) and statistical analysis were performed. Receiver operating characteristic (ROC) curves were used to assess prognostic utility of biomarkers for mortality and RRT.Results: Eighty-four (84) metabolites were identified and quantified in each urine sample. Of these, 11 were identified as drugs or drug metabolites and excluded. The PLS-DA models for ISS and AKI diagnosis did not have acceptable model statistics. Therefore, only mortality/RRT and AKI stage were analyzed further. Of 73 analyzed metabolites, 9 were significantly associated with mortality/RRT (p < 0.05) and 11 were significantly associated with AKI stage (p < 0.05). 1-Methylnicotinamide was the only metabolite to be significantly associated (p < 0.05) with all outcomes and was significantly higher (p < 0.05) in patients with adverse outcomes. Elevated lactate and 1-methylnicotinamide levels were associated with higher AKI stage and mortality and RRT, whereas elevated glycine levels were associated with patients who survived and did not require RRT, or had less severe AKI. ROC curves for each of these metabolites and the combined panel had good predictive value (lactate AUC = 0.901, 1-methylnicotinamide AUC = 0.864, glycine AUC = 0.735, panel AUC = 0.858).Conclusions: We identified urinary metabolites associated with AKI stage and the primary outcome of mortality or need for RRT. Lactate, 1-methylnicotinamide, and glycine may be used as a panel of predictive biomarkers for mortality and RRT. 1-Methylnicotinamide is a novel biomarker associated with adverse outcomes. Additional studies are necessary to determine how these metabolites can be utilized in clinically-relevant risk prediction models.

Importance: While brain cancer is rare, it has a very poor prognosis and few established risk factors. To date, epidemiologic work examining the potential association of traumatic brain injury (TBI) with the subsequent risk of brain cancer is conflicting. Further data may be useful.Objective: To examine whether a history of TBI exposure is associated with the subsequent development of brain cancer.Design, Setting, and Participants: A retrospective cohort study was conducted from October 1, 2004, to September 20, 2019, and data analysis was performed between January 1 and June 26, 2023. The median follow-up for the cohort was 7.2 (IQR, 4.1-10.1) years. Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1 919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium–Chronic Effects of Neurotrauma Consortium were included.Exposure: The main exposure of interest was TBI severity (categorized as mild, moderate or severe [moderate/severe], and penetrating).Main Outcomes and Measures: The outcome of interest was the development of brain cancer based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes in either the DoD/VA medical records or from the National Death Index.Results: After 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1 919 740 veterans was included, most of whom were male (80.25%) and non-Hispanic White (63.11%). Median age at index date was 31 (IQR, 25-42) years. The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating, 17 173). Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%). After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90; 95% CI, 1.16-3.12) and penetrating TBI (AHR, 3.33; 95% CI, 1.71-6.49), but not mild TBI (AHR, 1.14; 95% CI, 0.88-1.47), were associated with the subsequent development of brain cancer.Conclusions and Relevance: In this cohort study of veterans of the Iraq and Afghanistan wars, moderate/severe TBI and penetrating TBI, but not mild TBI, were associated with the subsequent development of brain cancer.