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Objective Randomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity. Methods Eligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported. Results Patients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy). Conclusion This observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population. Key Points• Patients with rheumatoid arthritis (RA) often require switching between biologics or targeted synthetic (b/ts) disease-modifying anti-rheumatic drugs (DMARDs) to achieve their treatment target.• Head-to-head randomized controlled trials (RCTs) in biologic-naïve RA patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy; however, there are no RCTs comparing these therapies in a population previously treated with b/tsDMARDs (i.e., b/ts-experienced patients).• This observational study compared the effectiveness of TNFi vs IL-6Ri (as mono- or combination therapy) in b/ts-experienced RA patients with moderate or high disease activity and found no significant differences in clinical outcomes for the two treatments.• A discrepancy is noted between our study and RCTs, which have shown superiority of IL-6Ri therapy (albeit in biologic-naïve patients). Further analyses may help elucidate the reason for this discrepancy in the real-world b/ts-experienced population.

Introduction Over the last two decades, the conflicts in Iraq and Afghanistan have cost the United States significantly in terms of lives lost, disabling injuries, and budgetary expenditures. This manuscript calculates the differences in costs between veterans with combat injuries vs veterans without combat injuries. This work could be used to project future costs in subsequent studies. Materials and Methods In this retrospective cohort study, we randomly selected 7,984 combat-injured veterans between February 1, 2002, and June 14, 2016, from Veterans Affairs Health System administrative data. We matched injured veterans 1:1 to noninjured veterans on year of birth (± 1 year), sex, and first service branch. We observed patients for a maximum of 10 years. This research protocol was reviewed and approved by the David Grant USAF Medical Center institutional review board (IRB), the University of Utah IRB, and the Research Review Committee of the VA Salt Lake City Health Care System in accordance with all applicable Federal regulations. Results Patients were primarily male (98.1% in both groups) and White (76.4% for injured patients, 72.3% for noninjured patients), with a mean (SD) age of 26.8 (6.6) years for the injured group and 27.7 (7.0) years for noninjured subjects. Average total costs for combat-injured service members were higher for each year studied. The difference was highest in the first year ($16,050 compared to $4,135 for noninjured). These differences remained significant after adjustment. Although this difference was greatest in the first year (marginal effect $12,386, 95% confidence interval $9,736-$15,036; P Conclusions Combat injured patients have significantly higher long-term health care costs compared to their noninjured counterparts. If this random sample is extrapolated to the 53,251 total of combat wounded service members, it implies a total excess cost of $1.6 billion to date after adjustment for covariates and a median follow-up time of 10 years. These costs are likely to increase as injured veterans age and develop additional chronic conditions.

Introduction Falls are a leading mechanism of injury. Hospitalization and outpatient clinic visits due to fall injury are frequently reported among both deployed and non-deployed U.S. Military personnel. Falls have been previously identified as a leading injury second only to sports and exercise as a cause for non-battle air evacuations. Materials and Methods This retrospective study analyzed the Department of Defense Trauma Registry fall injury data from September 11, 2001 to December 31, 2018. Deployed U.S. Military personnel with fall listed as one of their mechanisms of injury were included for analysis. Results Of 31,791 injured U.S. Military personnel captured by the Department of Defense Trauma Registry within the study time frame, a total of 3,101 (9.8%) incurred injuries from falls. Those who had fall injuries were primarily 21 to 30 years old (55.4%), male (93.1%), Army (75.6%), and enlisted personnel (56.9%). The proportion of casualties sustaining injuries from falls generally increased through the years of the study. Most fall injuries were classified as non-battle injury (91.9%). Falls accounted for 24.2% of non-battle injury hospital admissions with a median hospital stay of 2 days. More non-battle-related falls were reported in Iraq-centric military operations (62.7%); whereas more battle-related falls were reported in Afghanistan-centric military operations (58.3%). Conclusions This study is the largest analysis of deployed U.S. Military personnel injured by falls to date. Highlighted are preventive strategies to mitigate fall injury, reduce workforce attrition, and preserve combat mission capability. Level of Evidence Level III Epidemiologic.

INTRODUCTION Atrial fibrillation and atrial flutter (AF/AFL), the most common atrial arrhythmias, have never been examined in combat casualties. In this study, we investigated the impact of traumatic injury on AF/AFL among service members with deployment history. METHODS Sampled from the Department of Defense (DoD) Trauma Registry (n = 10,000), each injured patient in this retrospective cohort study was matched with a non-injured service member drawn from the Veterans Affairs/DoD Identity Repository. The primary outcome was AF/AFL diagnosis identified using ICD-9-CM and ICD-10-CM codes. Competing risk regressions based on Fine and Gray subdistribution hazards model with were utilized to assess the association between injury and AF/AFL. RESULTS There were 130 reported AF/AFL cases, 90 of whom were injured and 40 were non-injured. The estimated cumulative incidence rates of AF/AFL for injured was higher compared to non-injured patients (hazards ratio [HR] = 2.04; 95% confidence interval [CI] = 1.44, 2.87). After adjustment demographics and tobacco use, the association did not appreciably decrease (HR = 1.90; 95% CI = 1.23, 2.93). Additional adjustment for obesity, hypertension, diabetes, and vascular disorders, the association between injury and AF/AFL was no longer statistically significant (HR = 1.51; 95% CI = 0.99, 2.52). CONCLUSION Higher AF/AFL incidence rate was observed among deployed service members with combat injury compared to servicemembers without injury. The association did not remain significant after adjustment for cardiovascular-related covariates. These findings highlight the need for combat casualty surveillance to further understand the AF/AFL risk within the military population and to elucidate the potential underlying pathophysiologic mechanisms.

Examinations of risk factors for suicide attempt in United States service members at high risk of mental health diagnoses, such as those with combat injuries, are essential to guiding prevention and intervention efforts.Retrospective cohort study of 8727 combat-injured patients matched to deployed, non-injured patients utilizing Department of Defense and Veterans Affairs administrative records.Combat injury was positively associated with suicide attempt in the univariate model (HR = 1.75, 95% CI 1.5-2.1), but lost significance after adjustment for mental health diagnoses. Utilizing Latent Transition Analysis in the combat-injured group, we identified five mental/behavioral health profiles: (1) Few mental health diagnoses, (2) PTSD and depressive disorders, (3) Adjustment disorder, (4) Multiple mental health comorbidities, and (5) Multiple mental health comorbidities with alcohol use disorder (AUD). Multiple mental health comorbidities with AUD had the highest suicide attempt rate throughout the study and more than four times that of Multiple mental health comorbidities in the first study year (23.4 vs. 5.1 per 1000 person years, respectively).Findings indicate that (1) combat injury's impact on suicide attempt is attenuated by mental health and (2) AUD with multiple mental health comorbidities confers heightened suicide attempt risk in combat-injured service members.

BACKGROUND Military operations vary by scope, purpose, and intensity, each having unique forces and actions to execute a mission. Evaluation of military operation fatalities guides current and future casualty care. METHODS A retrospective study was conducted of all US military fatalities from Operation New Dawn in Iraq, 2010 to 2011. Data were obtained from autopsies and other records. Population characteristics, manner of death, cause of death, and location of death were analyzed. All fatalities were evaluated for concomitant evidence of underlying atherosclerosis. Nonsuicide trauma fatalities were also reviewed for injury severity, mechanism of death, injury survivability, death preventability, and opportunities for improvement. RESULTS Of 74 US military Operation New Dawn fatalities (median age, 26 years; male, 98.6%; conventional forces, 100%; prehospital, 82.4%) the leading cause of death was injury (86.5%). The manner of death was primarily homicide (55.4%), followed by suicide (17.6%), natural (13.5%), and accident (9.5%). Fatalities were divided near evenly between combatants (52.7%) and support personnel (47.3%), and between battle injury (51.4%) and disease and nonbattle injury (48.6%). Natural and suicide death was higher (p < 0.01, 0.02) among support personnel who were older (p = 0.05) with more reserve/national guard personnel (p = 0.01). Total population prevalence of underlying atherosclerosis was 18.9%, with more among support personnel (64.3%). Of 46 nonsuicide trauma fatalities, most died of blast injury (67.4%) followed by gunshot wound (26.1%) and multiple/blunt force injury (6.5%). The leading mechanism of death was catastrophic tissue destruction (82.6%). Most had nonsurvivable injuries (82.6%) and nonpreventable deaths (93.5%). CONCLUSION Operation New Dawn fatalities were exclusively conventional forces divided between combatants and support personnel, the former succumbing more to battle injury and the latter to disease and nonbattle injury including self-inflicted injury. For nonsuicide trauma fatalities, none died from a survivable injury, and 17.4% died from potentially survivable injuries. Opportunities for improvement included providing earlier blood products and surgery. LEVEL OF EVIDENCE Therapeutic, level V and epidemiological, level IV.

Previous studies have identified combat exposure and combat traumatic experience as problematic drinking risk factors. Increasing evidence suggests that opioid use increases the risk of alcohol use disorder. This study investigated the association between opioid prescription use after injury and (1) alcohol use disorder and (2) severity of alcohol use disorder among deployed military servicemembers.Deidentified health records data of 9,029 deployed servicemembers from a retrospective cohort study were analyzed. Data were randomly selected from the Department of Defense Trauma Registry and included servicemembers with combat injuries during deployment in Iraq or Afghanistan (2002-2016). Pharmacy records and International Classification of Diseases, Ninth and Tenth Revision diagnosis codes were used. Three groups were identified (no opioid prescription use, nonpersistent opioid prescription use, and persistent opioid prescription use) and were compared on the basis of alcohol use disorder risk using Cox proportional hazard models. Data analyses were performed in 2021.Of the 9,029 servicemembers with combat injury, 2,262 developed alcohol use disorder (1,322 developed severe alcohol use disorder). Compared with no opioid prescription use, increased alcohol use disorder risk was associated with persistent opioid prescription use, with a hazard ratio of 1.13 (95% CI=1.02, 1.26). After covariate adjustment, increased risk remained statistically significant (hazards ratio=1.24; 95% CI=1.10, 1.39). There was no significant difference in alcohol use disorder risk between no opioid prescription use and nonpersistent opioid prescription use. The risk of severe alcohol use disorder did not vary by opioid use among servicemembers with alcohol use disorder diagnosis.The findings of the study suggest that the incidence of alcohol use disorder was higher among injured servicemembers with persistent opioid prescription use than among those without opioid use. If replicated in prospective studies, the findings highlight the need for clinicians to consider the current and history of alcohol use of patients in initiating treatment involving opioids.