Self-Described Training Needs of Special Operations Forces Medics and the Birth of the TACMED Division.

Training needs of Special Operations Forces (SOF) medics were surveyed and new training initiatives have been created to meet their needs. SOF medics perform an array of medical procedures in austere environments with minimal supervision. Medical skills decay over time after initial training and the perceived training needs of active SOF medics were unclear. To fill this gap, active SOF medics (n=57) completed a survey that included confidence ratings and indications of whether additional training would make them more proficient in 70 medical knowledge and procedural skills, assembled into categories by a panel of experts (airway, trauma, neuro, differential diagnosis, administrative, infection, critical care, environmental, other). Data were analyzed with analysis of variance (ANOVA) and nonparametric statistics at P<.05. Confidence was highest in the trauma, administrative, and airway categories, and lowest in the infection, differential diagnosis, and neuro categories (P<.05 or less). Categories indicating the greatest need for additional training were environmental and critical care, while those indicating lowest need were the airway and trauma categories (P=.05). Additional training was endorsed by >75% of participants in each category. SOF medics also wanted additional training in all areas, preferably hands-on with live patients in realistic scenarios, taught by experienced medics. Findings highlight the training needs of SOF medics and demonstrate the value of bottom-up feedback toward optimizing sustainment training. Based on present findings, two TACMED (Tactical Medicine) Divisions at the SOF Echelon III level were created to meet the sustainment training needs of SOF medics.

Inhibition of mevalonate pathway by macrophage-specific delivery of atorvastatin prevents their pro-inflammatory polarisation.

Adjustment of the cellular metabolism of pro-inflammatory macrophages is essential for their bactericidal function; however, it underlies the development of many human diseases if induced chronically. Therefore, intervention of macrophage metabolic polarisation has been recognised as a potent strategy for their treatment. Although many small-molecule inhibitors affecting macrophage metabolism have been identified, their in vivo administration requires a tool for macrophage-specific delivery to limit their potential side effects. Here, we establish Drosophila melanogaster as a simple experimental model for in vivo testing of macrophage-specific delivery tools. We found that yeast-derived glucan particles (GPs) are suitable for macrophage-specific delivery of small-molecule inhibitors. Systemic administration of GPs loaded with atorvastatin, the inhibitor of hydroxy-methyl-glutaryl-CoA reductase (Hmgcr), leads to intervention of mevalonate pathway specifically in macrophages, without affecting HMGCR activity in other tissues. Using this tool, we demonstrate that mevalonate pathway is essential for macrophage pro-inflammatory polarisation and individual's survival of infection.

Accelerated reactive dissolution model of drug release from long-acting injectable formulations.

Long-acting injectable formulations represent a rapidly emerging category of drug delivery systems that offer several advantages compared to orally administered medicines. Rather than having to frequently swallow tablets, the medication is administered to the patient by intramuscular or subcutaneous injection of a nanoparticle suspension that forms a local depot from which the drug is steadily released over a period of several weeks or months. The benefits of this approach include improved medication compliance, reduced fluctuations of drug plasma level, or the suppression of gastrointestinal tract irritation. The mechanism of drug release from injectable depot systems is complex, and there is a lack of models that would enable quantitative parametrisation of the process. In this work, an experimental and computational study of drug release from a long-acting injectable depot system is reported. A population balance model of prodrug dissolution from asuspension with specific particle size distribution has been coupled with the kinetics of prodrug hydrolysis to its parent drug and validated using in vitro experimental data obtained from an accelerated reactive dissolution test. Using the developed model, it is possible to predict the sensitivity of drug release profiles to the initial concentration and particle size distribution of the prodrug suspension, and subsequently simulate various drug dosing scenarios. Parametric analysis of the system has identified the boundaries of reaction- and dissolution-limited drug release regimes, and the conditions for the existence of a quasi-steady state. This knowledge is crucial for the rational design of drug formulations in terms of particle size distribution, concentration and intended duration of drug release.