Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association between SCT and ERM is poorly understood. The objective of this study was to elucidate the genetic basis of ERM in an SCT-positive African American cohort. SCT-positive African Americans with a personal history of ERM (cases, n = 30) and without history of ERM (controls, n = 53) were enrolled in this study. Whole-genome sequencing was performed on DNA samples isolated from peripheral white blood cells. Participants’ demographic, behavioral, and medical history information was obtained. An additional 131 controls were extracted from SCT-positive subjects of African descent from the 1000 Genomes Project. SCT carriers with ERM were characterized by myotoxicity features, significant muscle involvement dominated by muscle weakness, and severe pain and substantial increase in serum creatine kinase, with a mean value of 50,480 U/L. A distinctive feature of the SCT individuals with ERM was exertional collapse, which was reported in 53.3% of the cases in the study cohort. An important factor for the development of ERM was the duration and frequency of strenuous physical activity in the cases compared to the controls. Whole-genome sequencing identified 79,696 protein-coding variants. Genome-wide association analysis revealed that the p.C477R, rs115958260 variant in the SLC44A3 gene was significantly associated with ERM event in SCT-positive African Americans. The study results suggest that a combination of vigorous exercise and a genetic predisposing factor is involved in ERM.

Context: The US Army embedded injury-prevention experts (IPEs), specifically athletic trainers and strength and conditioning coaches, into initial entry training (IET) to limit musculoskeletal (MSK) conditions and their negative consequences. However, little is known about the financial impact of IPEs. Objective: To assess whether IPEs were associated with fewer sunk training costs due to MSK-related early discharges from service. Design: Retrospective cohort study. Setting: Database of US Army soldiers’ administrative, medical, and readiness records. Patients or Other Participants: A total of 198 166 soldiers (age = 20.7 ± 3.2 years, body mass index = 24.4 ± 3.5 kg/m2) who began IET during 2014 to 2017. Main Outcome Measure(s): Early discharge from service was defined as occurring within 6 months of beginning IET. All IET sites employed IPEs from 2011 to 2017, except for 2 sites during April to November 2015. Soldiers who began IET at these 2 sites during these times were categorized as not having IPE exposure. All others were categorized as having IPE exposure. The unadjusted association between IPE access and MSK-related early discharge from service was assessed using logistic regression. Financial impact was assessed by quantifying differences in yearly sunk costs between groups with and those without IPE exposure and subtracting IPE hiring costs. Results: Among 14 094 soldiers without IPE exposure, 2.77% were discharged early for MSK-related reasons. Among 184 072 soldiers with IPE exposure, 1.01% were discharged. Exposure to IPEs was associated with reduced odds of MSK-related early discharge (odds ratio = 0.36, 95% CI = 0.32, 0.40, P < .001) and a decrease in yearly sunk training costs of $11.19 to $20.00 million. Conclusions: Employing IPEs was associated with reduced sunk costs because of fewer soldiers being discharged from service early for MSK-related reasons. Evidence-based recommendations should be developed for guiding policy on the roles and responsibilities of IPEs in the military to reduce negative outcomes from MSK conditions and generate a positive return on investment.