Purpose: Remdesivir use in COVID-19 is associated with cardiac conduction abnormalities from unclear mechanisms. A proposed mechanism is the bioaccumulation of the intermediate metabolite GS-441524 resulting in exogenous activation of cardiac adenosine A1 due to the structural similarity between adenosine and GS-441524. The prolonged half-life of GS-441524 can result in sustained activation of adenosine A1 receptors. In this study, we used molecular modeling of adenosine, GS-441524 and the adenosine A1 receptor to assess the potential mechanistic association of the proposed mechanism.Methods: Adenosine and GS-441524 structures were acquired from the PubChem database. Ligand docking was carried out using UCSF Chimera. Models were chosen based on greatest binding affinity and minimum root mean square deviation. Figures of resulting structural models were prepared using UCSF Chimera or PyMOL 2.3.5.Results: By modeling the interaction between the A1 G protein complex and both adenosine and GS-441524, we found that the proposed mechanism of exogenous A1 receptor activation is feasible based on docking compatibility.Conclusion: The proposed mechanism of exogenous cardiac A1 receptor activation from bioaccumulation of GS-441524 as a cause of observed cardiac conduction abnormalities with the use of remdesivir in COVID-19 is viable. Further studies are needed to assess causality.
<b>Background:</b> Inclusion of point-of-care ultrasound (POCUS) within medical education is increasing. A lack of clinical preceptors ready to teach POCUS to physician assistant (PA) students has been discovered. Understanding the barriers to student use of POCUS in clinical education will inform curricular planning.<br /> <b>Methods:</b> Qualitative survey research was completed on 212 previously identified PA student preceptors. Descriptive statistics outlining frequencies of responses were completed.<br /> <b>Results:</b> The most frequently identified barriers included lack of preceptor experience with POCUS (63.7%), lack of access to a device (47.6%), and lack of familiarity with POCUS (45.2%). Time and lack of experience with POCUS were more commonly identified by inpatient providers. Lack of clinical indications and device access were more frequent in outpatient preceptors.<br /> <br /> <b>Discussion:</b> As programs incorporate POCUS, creating intentional opportunities for POCUS education on clinical rotations is needed. The differences in barriers based on practice type allow targeted intervention based on specific rotations.
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