Two for One: Merging Continuing Professional Development and Faculty Development in the CATE Curriculum for Pharmacy Preceptors.

Background: Continuing professional development (CPD) and faculty development (FD) are not traditionally combined, although there is evidence that integrating them enhances knowledge acquisition. Objective: To explore preceptors' perceptions and the effectiveness of CATE (Clinical And Teaching Education), an education model that blends clinical content with the application of that clinical knowledge through a specified teaching technique. Methods: Thirty-five hospital and community pharmacy preceptors from the Leslie Dan Faculty of Pharmacy, University of Toronto, participated in CATE, which consisted of a 2-hour synchronous, online workshop integrating clinical content about depression with the "One-Minute Preceptor" (OMP) teaching skill. Qualitative and quantitative data were collected longitudinally using surveys and semistructured interviews. Participant and process outcomes were explored through descriptive and thematic analysis using a modified Kirkpatrick framework. Results: Participants valued the incorporation of educational theory and opportunities to practise the OMP using scripted role plays based on the depression-related content. The combination of FD and CPD was appealing, although participants wanted more clarity about their integration. The CATE model positively influenced their approaches to serving as preceptors, and using the OMP helped to reveal learners' knowledge gaps. There was a desire to share the teaching technique with colleagues to provide a more cohesive approach to teaching. Conclusions: Integrating CPD and FD in a synchronous, online environment was feasible and well received, and it helped to solidify preceptors' roles as educators. Combining CPD and FD represents an effective strategy to build the clinical and educational expertise of preceptors, which in turn has the potential to improve the quality of experiential learning for pharmacy students. This novel method of fostering the pedagogical growth of preceptors could be a model for other health professions.

Contexte: Le développement professionnel continu (DPC) et le développement professoral (DP) ne sont pas traditionnellement combinés, même s'il existe des éléments probants indiquant que leur intégration renforce l'acquisition des connaissances. Objectif: Examiner les perceptions des précepteurs et l'efficacité du CATE (Clinical And Teaching Education): un modèle pédagogique qui allie le contenu clinique à l'application de ces connaissances cliniques grâce à une technique d'enseignement spécifiée. Méthodologie: Trente-cinq précepteurs de pharmacies d'hôpitaux et communautaires de la Faculté de pharmacie Leslie Dan de l'Université de Toronto ont participé au CATE, qui consistait en un atelier en ligne synchrone de deux heures intégrant un contenu clinique sur la dépression avec la compétence pédagogique « précepteur-minute ¼. Les données qualitatives et quantitatives ont été recueillies longitudinalement à l'aide d'enquêtes et d'entretiens semi-structurés. Les résultats des participants et du processus ont été étudiés au moyen d'une analyse descriptive et thématique utilisant un cadre de Kirkpatrick modifié. Résultats: Les participants ont apprécié l'intégration de la théorie pédagogique et des occasions de pratiquer la compétence du précepteur-minute à l'aide de jeux de rôle scénarisés basés sur le contenu lié à la dépression. La combinaison du DP et du DPC était attrayante, même si les participants souhaitaient plus de clarté sur leur intégration. Le modèle CATE a influencé positivement leurs approches en matière de préceptorat, et l'utilisation de la technique précepteur-minute a contribué à révéler les lacunes des connaissances des apprenants. Il y avait une volonté de partager la technique d'enseignement avec des collègues pour offrir une approche plus cohérente de l'enseignement. Conclusions: L'intégration du DPC et du DP dans un environnement en ligne synchrone était réalisable et a été bien accueillie; elle a contribué à consolider le rôle des précepteurs en tant qu'éducateurs. La combinaison du DPC et du DP constitue une stratégie efficace pour développer l'expertise clinique et pédagogique des précepteurs, ce qui, à son tour, a le potentiel d'améliorer la qualité de l'apprentissage expérientiel des étudiants en pharmacie. Cette nouvelle méthode visant à favoriser la croissance pédagogique des précepteurs pourrait constituer un modèle pour d'autres professions de la santé.

Activation of PXR causes drug interactions with Paxlovid in transgenic mice.

Paxlovid is a nirmatrelvir (NMV) and ritonavir (RTV) co-packaged medication used for the treatment of coronavirus disease 2019 (COVID-19). The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster. Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid. By using recombinant human cytochrome P450s (CYPs), we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism. The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice, which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV. Pregnane X receptor (PXR) is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression. We next explored the impact of drug- and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5. We found that PXR activation increased CYP3A4/5 expression, accelerated NMV metabolism, and reduced the systemic exposure of NMV. In summary, our work demonstrated that PXR activation can cause drug interactions with Paxlovid, suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.

Coronavirus Related Mortality in the Geriatrics Ambulatory Practice.

BACKGROUND: Older adults often have atypical presentations of common diseases and COVID-19 is no exception. Presentations range from asymptomatic to overwhelming symptoms that result in hospitalization, intubation, or death. The number of COVID-19 related deaths among older adults in the outpatient practice during the peak of the pandemic is unclear. METHODS: The objective is to describe the COVID-19 status and clinical characteristics of patients in a Geriatrics Ambulatory Practice who died during the peak of the COVID-19 pandemic. Design: Retrospective chart review Participants: 54 adults age 65 years and older. Methods: COVID-19 status defined by positive test result and presumed COVID-19 status based upon clinical presentation. RESULTS: Out of 1200 active patients in the Geriatrics Ambulatory Practice, 54 (4.5%) died between January 1st, 2020 and June 30th, 2020. The study sample was 63% female, 33% Hispanic/Latino, 27% Black/African American, and 22% white. The mean (SD) age was 86(8.6) years, range (72-107 years). The most prevalent medical comorbidities in decreasing order of frequency were hypertension (88.9%), diabetes (51.9%), and cognitive impairment (51.9%). Nineteen (35%) were COVID-19 positive and 8 had presumed COVID-19. There were no statistically significant differences in age, gender, race/ethnicity, and medical comorbidities between the COVID-19 or presumed COVID-19 group compared to those with No COVID-19. CONCLUSION: Approximately 35% of Geriatric patients who died during the first 6 months of 2020 had confirmed COVID-19 and an additional 15% had presumed COVID-19. The actual number of COVID-19 related deaths among older adults in the ambulatory practice during the peak of the pandemic is difficult to estimate and likely underestimated.

Global Extraintestinal Pathogenic Escherichia coli (ExPEC) Lineages.

Extraintestinal pathogenic Escherichia coli (ExPEC) strains are responsible for a majority of human extraintestinal infections globally, resulting in enormous direct medical and social costs. ExPEC strains are comprised of many lineages, but only a subset is responsible for the vast majority of infections. Few systematic surveillance systems exist for ExPEC. To address this gap, we systematically reviewed and meta-analyzed 217 studies (1995 to 2018) that performed multilocus sequence typing or whole-genome sequencing to genotype E. coli recovered from extraintestinal infections or the gut. Twenty major ExPEC sequence types (STs) accounted for 85% of E. coli isolates from the included studies. ST131 was the most common ST from 2000 onwards, covering all geographic regions. Antimicrobial resistance-based isolate study inclusion criteria likely led to an overestimation and underestimation of some lineages. European and North American studies showed similar distributions of ExPEC STs, but Asian and African studies diverged. Epidemiology and population dynamics of ExPEC are complex; summary proportion for some STs varied over time (e.g., ST95), while other STs were constant (e.g., ST10). Persistence, adaptation, and predominance in the intestinal reservoir may drive ExPEC success. Systematic, unbiased tracking of predominant ExPEC lineages will direct research toward better treatment and prevention strategies for extraintestinal infections.

Differential cholesterol binding by class II fusion proteins determines membrane fusion properties.

The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. These fusion proteins are triggered by low pH, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. Here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. Using cholesterol-depleted insect cells, we showed that fusion and infection by the alphaviruses Semliki Forest virus (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar sterol dependence in laboratory and field isolates and in viruses passaged in tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by labeling with photocholesterol and by cholesterol extraction studies. In contrast, fusion and infection by numerous strains of the flavivirus dengue virus (DV) and by yellow fever virus 17D were cholesterol independent, and the DV fusion protein did not show significant cholesterol binding. SFV E1 is the first virus fusion protein demonstrated to directly bind cholesterol. Taken together, our results reveal important functional differences conferred by the cholesterol-binding properties of class II fusion proteins.