Medication errors cause preventable patient harm with annual costs of USD$42 billion globally. In England, 237 million errors occur annually, accounting for 1700 deaths, with trainee doctors being responsible for the highest proportion of errors. The UK introduced the national Prescribing Safety Assessment (PSA) in 2013 to ensure prescribing competency. Imperial College School of Medicine (ICSM) sought to increase learning opportunities and reduce errors through a monthly Prescribing Practice Questions (PPQs) programme. PSA scores from 2020 (prior to PPQ introduction) to 2024 (first cohort to receive entire PPQ programme), the prescription writing skills (PWS) subsection and applied knowledge test (AKT) scores in 2020 and 2024 were analysed. 1505 students sat the PSA between 2020 and 2024. PSA fails significantly reduced from 2.51% in 2020 to 0% in 2024 (p=0.0054). Median PSA scores significantly improved from 78.5% in 2020 to 84.0% in 2024 (p<0.0001). Median AKT scores decreased between 2020 and 2024 (78.0% vs 74.5%, p<0.0001). Absolute increase in PSA scores from lowest to highest quintiles was 10 percentage points (pp), 7pp, 5pp, 4pp and 1pp, respectively, between 2020 and 2024. Median PWS scores significantly improved from 76.3 % (61/80) in 2020 to 87.5% (70/80) in 2024 (p<0.0001). Since introducing PPQs, PSA and PWS scores have statistically significantly improved, with progressively greater impact on students at the bottom of the performance distribution. Early, targeted and repeated opportunities for authentic prescribing activities, such as the PPQs, in undergraduate training may lead to significant improvement in prescribing competency as determined by the PSA.

Background The 18kDa Translocator Protein (TSPO) has been proposed as a novel anti-inflammatory drug target. XBD173 and etifoxine are TSPO ligands that modulate inflammatory responses in preclinical models. Limited pharmacokinetic data is available publicly for either molecule. Purpose To derive pharmacokinetic data for orally administered etifoxine and XBD173 in humans and determine the binding affinity of etifoxine for TSPO. Experimental Approach We measured plasma concentrations serially after dosing 4 healthy volunteers with XBD173 90mg once a day (OD) for 7 days or etifoxine 50mg three times a day (TDS) for 7 days. We separately performed competition assays between etifoxine and [3H]PK11195 in human brain tissue to determine its TSPO binding affinity. Key Results The average XBD173 Cmax was 129 ng/mL with free fraction was 0.34%, predicting a maximal free concentration of 1.1 nM. For etifoxine, the average plasma Cmax was 32 ng/mL with a free fraction of 0.29%, predicting a maximal free etifoxine concentration of 0.31 nM. The Ki for etifoxine in human brain was 7.8uM (95% CI 4.5-14.6uM) Conclusion Oral XBD173 dosing at 90mg OD will achieve pharmacologically relevant TSPO occupancy. However, the occupancy is too low for TSPO mediated effects after oral dosing of etifoxine at 50mg TDS. Implications Our pharmacokinetic and brain affinity data suggest that physiological effects of oral XBD173 could be mediated by TSPO, but that any physiological effects of oral etifoxine cannot be a consequence of direct interaction with this target.