Lifetime Traumatic Brain injury and Risk of Post-Concussive Symptoms in the Millennium Cohort Study

Traumatic brain injury (TBI) is prevalent among active duty military service members, with studies reporting up to 23% experiencing at least one TBI, with 10-60% of service members reporting at least one subsequent repeat TBI. A TBI has been associated with an increased risk of cumulative effects and long-term neurobehavioral symptoms, impacting operational readiness in the short-term and overall health in the long term. The association between multiple TBI and post-concussive symptoms (PCS), however, defined as symptoms that follow a concussion or TBI, in the military has not been adequately examined. Previous studies in military populations are limited by methodological issues including small sample sizes, the use of non-probability sampling, or failure to include the total number of TBI. to overcome these limitations, we examined the association between the total lifetime number of TBI and total number of PCS among U.S. active duty military service members who participated in the Millennium Cohort Study. A secondary data analysis was conducted using the Millennium Cohort Study\u27s 2014 survey

Occupation and Risk of Traumatic Brain injury in the Millennium Cohort Study

INTRODUCTION: Traumatic brain injury (TBI) is an occupational health hazard of military service. Few studies have examined differences in military occupational categories (MOC) which take into consideration the physical demands and job requirements across occupational groups. METHODS: This study was approved by the University of Texas Health Science Center at Houston Institutional Review Board. Data for this cross-sectional study were obtained from the Naval Health Research Center\u27s Millennium Cohort Study, an ongoing DoD study. Univariate analyses were employed to calculate frequencies and proportions for all variables. Bivariate analyses included unadjusted odds ratios (OR) and 95% CI for the association between all variables and TBI. Multivariable logistic regression was used to calculate adjusted ORs and 95% CIs to assess the association between MOC and TBI, adjusted for potential confounders: sex, race/ethnicity, rank, military status, branch of service, before-service TBI, and panel. Logistic regression models estimated odds of TBI for each MOC, and stratified models estimated odds separately for enlisted and officer MOCs. RESULTS: Approximately 27% of all participants reported experiencing a service-related TBI. All MOCs were statistically significantly associated with increased odds of service-related TBI, with a range of 16 to 45%, except for Health Care MOCs (OR: 1.01, 95% CI 0.91-1.13). Service members in Infantry/Tactical Operations had the highest odds (OR: 1.45, 95% CI 1.31-1.61) of service-related TBI as compared to Administration & Executives. Among enlisted service members, approximately 28% reported experiencing a service-related TBI. Among enlisted-specific MOCs, the odds of TBI were elevated for those serving in Infantry, Gun Crews, Seamanship (OR: 1.79, 95% CI 1.58-2.02), followed by Electrical/Mechanical Equipment Repairers (OR: 1.23, 95% CI 1.09-1.38), Service & Supply Handlers (OR 1.21, 95% CI 1.08-1.37), Other Technical & Allied Specialists (OR 1.21, 95% CI 1.02-1.43), Health Care Specialists (OR 1.19, 95% CI 1.04-1.36), and Communications & Intelligence (OR: 1.16, 95% CI 1.02-1.31), compared to Functional Support & Administration. Among officer service members, approximately 24% reported experiencing a service-related TBI. After adjustment the odds of TBI were found to be significant for those serving as Health Care Officers (OR: 0.65, 95% CI: 0.52-0.80) and Intelligence Officers (OR: 1.27, 95% CI: 1.01-1.61). CONCLUSIONS: A strength of this analysis is the breakdown of MOC associations with TBI stratified by enlisted and officer ranks, which has been previously unreported. Given the significantly increased odds of service-related TBI reporting within enlisted ranks, further exploration into the location (deployed versus non-deployed) and mechanism (e.g., blast, training, sports, etc.) for these injuries is needed. Understanding injury patterns within these military occupations is necessary to increase TBI identification, treatment, and foremost, prevention.Results highlight the importance of examining specific occupational categories rather than relying on gross categorizations, which do not account for shared knowledge, skills, and abilities within occupations. The quantification of risk among enlisted MOCs suggests a need for further research into the causes of TBI

The Association of Self-Reported Measures With Poor Training Outcomes Among Male and Female US Navy Recruits

This prospective study evaluated the association of self-reported health habits and behaviors in 2,930 Navy recruits with poor training outcomes, defined as graduating late or separating from training. Although 17% of the men and 21% of the women had a poor training outcome, results suggest that some self-reported measures were associated with poor training outcomes. Men who did not run or jog at least 1 month before basic training or had a previous lower limb injury without complete recovery and women reporting the same or less physical activity compared with their same-age counterparts were more likely to have a poor training outcome. An important first step in decreasing poor training outcomes is encouraging incoming recruits to participate in physical activity and taking steps to identify and rehabilitate recruits who are not completely healed from a lower limb musculoskeletal injury before reporting to basic training

Self-Reported Smoking and Musculoskeletal Overuse Injury Among Male and Female US Marine Corps Recruits

The association between self-reported smoking and overuse injury in a cohort of young men (n=900) and women (n=597) undergoing 12 weeks of standardized military instruction, after adjustment for physical activity, health history, and incoming fitness tests was examined. The outcome includes all International Classification of Diseases, 9th Revision codes related to injuries resulting from cumulative microtrauma (overuse injuries). The short survey asked about the subject’s demographics, smoking habits, prior injuries sustained, physical activity level, selfperceived fitness, and (for women) menstrual history. From the survey, 4 questions established smoking behavior: smoked at least 100 cigarettes in lifetime, age smoked a whole cigarette for the first time, how many cigarettes smoked during the last 30 days, and how many cigarettes smoked per day during the last 30 days. None of the adjusted hazard ratios for the smoking questions were associated with an increased risk of overuse injury for either sex. Furthermore, this study did not find a significant association with respect to smoking and all injuries in either men or women. In conclusion, smoking does not appear to be an independent risk factor for overuse injury in either young men or women during 12 weeks of standardized military instruction

Prevalence, factors associated with use, and adverse effects of sport-related nutritional supplements (sport drinks, sport bars, sport gels): the US military dietary supplement use study

Background Sport-related nutritional supplements (SRNSs) include sport drinks, sport bars, and sport gels. Previous studies indicate that 25–35 % of athletes and 25–50 % of military personnel report using these supplements. This study examined prevalence, factors associated with use, and adverse effects (AEs) of SRNSs among United States military service members (SMs). Methods A stratified random sample of 200,000 SMs was obtained from military workforce records, and asked to complete a survey on demographics, SRNS use, and AEs experienced. About 18 % (n = 26,681) of contacted SMs (n = 146,365) completed the survey between December 2018 and August 2019. Results Overall, 45 % of SMs used ≥ 1 SRNS at least once per week in the past 6 months. Prevalence of use (± standard error) for sport drinks, bars, and gels were 32 ± 0.3, 27 ± 0.3, and 3 ± 0.1 %, respectively. Use of 1, 2, or 3 SRNSs was 28.9 ± 0.5, 13.6 ± 0.6, and 2.2 ± 0.6 %, respectively. Multivariable logistic regression indicated greater use of any SRNS was independently associated with male gender, younger age, single marital status, more weekly aerobic or resistance training, tobacco use, higher alcohol intake, officer status, combat arms occupations, and service in the Marine Corps or Navy (compared to the Air Force). Overall, the proportion of users reporting ≥ 1 AE was 2.0 ± 0.1 %, with 1.3 ± 0.1 % for sport drinks, 1.6 ± 0.2 % for sport bars, and 2.8 ± 0.6 % for sport gels. Conclusions This large study of a stratified random sample of SMs found that nearly half of SMs consumed SRNSs weekly, and self-reported AEs were comparatively low. The AE incidence for SRNSs was much lower than typically found for dietary supplements, possibly because of more rigorous regulatory oversight for SRNSs

Caffeine Use among Active Duty Navy and Marine Corps Personnel

Data from the National Health and Nutrition Examination Survey (NHANES) indicate 89% of Americans regularly consume caffeine, but these data do not include military personnel. This cross-sectional study examined caffeine use in Navy and Marine Corps personnel, including prevalence, amount of daily consumption, and factors associated with use. A random sample of Navy and Marine Corps personnel was contacted and asked to complete a detailed questionnaire describing their use of caffeine-containing substances, in addition to their demographic, military, and lifestyle characteristics. A total of 1708 service members (SMs) completed the questionnaire. Overall, 87% reported using caffeinated beverages ≥1 time/week, with caffeine users consuming a mean ± standard error of 226 ± 5 mg/day (242 ± 7 mg/day for men, 183 ± 8 mg/day for women). The most commonly consumed caffeinated beverages (% users) were coffee (65%), colas (54%), teas (40%), and energy drinks (28%). Multivariable logistic regression modeling indicated that characteristics independently associated with caffeine use (≥1 time/week) included older age, white race/ethnicity, higher alcohol consumption, and participating in less resistance training. Prevalence of caffeine use in these SMs was similar to that reported in civilian investigations, but daily consumption (mg/day) was higher

A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105

RET fusions are oncogenic drivers of various tumors, including non-small cell lung cancers (NSCLC). The safety and antitumor activity of the multikinase RET inhibitor RXDX-105 were explored in a phase I/Ib trial. A recommended phase II dose of 275 mg fed daily was identified. The most common treatment-related adverse events were fatigue (25%), diarrhea (24%), hypophosphatemia (18%), maculopapular rash (18%), and nonmaculopapular rash (17%). In the phase Ib cohort of RET inhibitor-naïve patients with RET fusion-positive NSCLCs, the objective response rate (ORR) was 19% (95% CI, 8%-38%, n = 6/31). Interestingly, the ORR varied significantly by the gene fusion partner (P < 0.001, Fisher exact test): 0% (95% CI, 0%-17%, n = 0/20) with KIF5B (the most common upstream partner for RET fusion-positive NSCLC), and 67% (95% CI, 30%-93%, n = 6/9) with non-KIF5B partners. The median duration of response in all RET fusion-positive NSCLCs was not reached (range, 5 to 18+ months). SIGNIFICANCE: Although KIF5B-RET is the most common RET fusion in NSCLCs, RET inhibition with RXDX-105 resulted in responses only in non-KIF5B-RET-containing cancers. Novel approaches to targeting KIF5B-RET-containing tumors are needed, along with a deeper understanding of the biology that underlies the differential responses observed.This article is highlighted in the In This Issue feature, p. 305

A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105

RET fusions are oncogenic drivers of various tumors, including non-small cell lung cancers (NSCLC). The safety and antitumor activity of the multikinase RET inhibitor RXDX-105 were explored in a phase I/Ib trial. A recommended phase II dose of 275 mg fed daily was identified. The most common treatment-related adverse events were fatigue (25%), diarrhea (24%), hypophosphatemia (18%), maculopapular rash (18%), and nonmaculopapular rash (17%). In the phase Ib cohort of RET inhibitor-naïve patients with RET fusion-positive NSCLCs, the objective response rate (ORR) was 19% (95% CI, 8%-38%, n = 6/31). Interestingly, the ORR varied significantly by the gene fusion partner (P \u3c 0.001, Fisher exact test): 0% (95% CI, 0%-17%, n = 0/20) with KIF5B (the most common upstream partner for RET fusion-positive NSCLC), and 67% (95% CI, 30%-93%, n = 6/9) with non-KIF5B partners. The median duration of response in all RETfusion-positive NSCLCs was not reached (range, 5 to 18+ months). SIGNIFICANCE: Although KIF5B-RET is the most common RET fusion in NSCLCs, RET inhibition with RXDX-105 resulted in responses only in non-KIF5B-RET-containing cancers. Novel approaches to targeting KIF5B-RET-containing tumors are needed, along with a deeper understanding of the biology that underlies the differential responses observed