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Introduction: Low physical activity (PA) and physical fitness (PF) are well-known factors for chronic diseases generally and cardiovascular diseases specifically. The economic burden from these chronic diseases is also well documented, as is their disproportionate prevalence among states in the Southern region of the U.S. Low PA and PF have also become recognized factors impacting military readiness and national security. Specifically, low PA and PF are highly correlated with musculoskeletal injures (MSKIs), now considered the greatest medical impediment to military readiness. Prior research shows low PF and MSKI incidence are greater among Army recruits from Southern states, however no previous research has investigated the economic impact of MSKIs at the state- and regional-level. The aim of this study was to determine the economic impact of MSKIs among U.S. Army initial military trainees on a state- and regional-basis.Methods: Rosters for recruits entering U.S. Army Initial Military Training (IMT) for fiscal year 2017 were obtained (n = 103,487). Roster data included the unique personal identifier, demographics with postal zip code, training start/end dates, and height and weight and were subsequently linked to medical encounters and cost data from the Military Health System Data Repository. Trainees with one or more MSKIs were considered injury cases (n = 33,509) and were stratified by gender. The percent of trainee MSKI cases was calculated as number of injury cases divided by total number of trainees. For each injury case, the direct medical cost for MSKIs was calculated. The percent of trainees and direct medical costs for MSKIs were aggregated to home-state and regional-levels for the four U.S. Census tract regions. A test for equality of proportions was performed at state- and regional-levels to investigate differences in percent of trainees with MSKIs by state/region. A one-way ANOVA was used to investigate possible differences in medical cost/trainee by region.Results: 34% (n = 33,509) of all trainees sustained at least one MSKI. State-specific MSKI percentages showed ten states having the greatest percentage of trainees with at least one MSKI, eight of which were from the South region (AL, FL, GA, LA, MS, NC, SC, TN). The South was the only region to have a statistically significantly higher percentage of trainees with MSKIs at 34% (p < 0.001), as compared to all other regions. The total direct medical cost of treating MSKIs among all trainees was $14,891,563. The South was the costliest region ($7,168,997), accounted for nearly 50 % of the total national cost, and had the highest mean MSKI cost/trainee.Discussion: This study was the first in demonstrating the disproportionate economic burden Southern states pose to the U.S. Department of Defense resulting from its significantly higher MSKI cost. PA and PF are known to ameliorate chronic disease and MSKI burden among general and military populations. Therefore, increasing PA and PF among all young Americans, and specifically those living in Southern states, is imperative for improving public health and reducing the economic and practical burden of MSKIs on military readiness and national security. [ABSTRACT FROM AUTHOR]