ImportancePlatelet activation is a potential therapeutic target in patients with COVID-19.ObjectiveTo evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.Design, Setting, and ParticipantsThis international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care–level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.InterventionParticipants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor.Main Outcomes and MeasuresThe primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis.ResultsAt the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support–free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77).Conclusions and RelevanceIn this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19.Trial RegistrationClinicalTrials.gov Identifier: NCT04505774
Mentorship is critical to the development and professional growth of graduate medical education (GME) trainees. It is a bidirectional relationship between a mentor and a mentee. Mentorship has consistently been shown to be beneficial for both the mentor and mentee, with the mentee gaining valuable skills in education, personal growth, and professional support, and the mentor attaining higher career satisfaction and potentially greater productivity. Yet, there is a lack of research and in-depth analysis of effective mentorship and its role in postgraduate medical education. This chapter outlines different approaches toward mentorship and provides the reader with basic concepts relevant to the effective and competent practice of mentorship. The authors discuss the challenges that physician mentors and mentees face, the organizational models of mentorship, the approaches and techniques for mentorship, and the deleterious effects of mentorship malpractice. Our general discussion touches on best practices for both the mentor and mentee to allow for self-improvement and lifelong learning. The variety of applicable models makes it difficult to measure effectiveness of mentorship in GME, but there is an ongoing need for expanded research on the benefits of mentorship, as greater amount of supporting evidence will likely incentivize organizations to create mentorship-friendly policies and support corresponding institutional changes.
Type 1 diabetes (T1D) affects many individuals worldwide and is associated with multiple long-term complications. The underlying pathophysiology of T1D involves an autoimmune process that leads to destruction of pancreatic β-islet cells, which are the sole cells responsible for producing the body’s insulin. Thus, the current recommended treatment for T1D is insulin therapy, which requires continuous awareness and monitoring throughout the day, placing a great deal of stress and responsibility on patients. Various modalities are under investigation to provide alternatives to treatment, or even a cure. Adult endogenous progenitor cells have been studied as one potential therapy for patients with T1D due to their ability to prevent an allogenic immune response in addition to an autoimmune response. Additionally, pancreatic ductal cells and bone marrow stem cells served as one of the first areas of research that demonstrated self-progenitor cells could regenerate pancreatic islet cells. A major limitation to stem cell therapy success is the risk of graft rejection. However, altering immune cell composition and creating physical barriers to protect the implanted cells from attack has been one successful solution to this by circumventing the pernicious immune response that is characteristic of T1D. Other limitations of these therapies include teratoma risk and the inability to reproduce the required signaling environment for cell differentiation ex vivo. Furthermore, stem cell therapy has shown promise in its applications for treatment of diabetes-associated complications including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. This article critically reviews previous research and current progress toward stem cell treatment options for patients with T1D.
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