Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial.

Importance: Platelet activation is a potential therapeutic target in patients with COVID-19. Objective: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: This 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. Intervention: Participants 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 Measures: The 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. Results: At 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 Relevance: In 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 Registration: ClinicalTrials.gov Identifier: NCT04505774.

Continued impact of COVID-19 pandemic on clinical and translational science early-career researchers.

The COVID-19 pandemic had an immediate impact on the lives and work of early-career researchers. We leveraged a cluster-randomized trial and compared survey data collected over two timepoints to explore whether these impacts persisted. Although more than a year had passed, 74% of participants reported that their research was affected in multiple ways in both 2020 and 2021. These data suggest that the effects of the pandemic on early-career researchers may be prolonged. Our findings additionally serve as an impetus to identify and implement solutions to early-career challenges that undoubtedly existed before the pandemic, but which COVID-19 brought into the spotlight.

A Mixed-Methods Analysis of Gender and Career Status Differences in the Impact of the COVID-19 Pandemic on Underrepresented Postdoctoral Fellows and Early-Career Faculty

Purpose The lack of racial and ethnic diversity in the biomedical workforce is pronounced and those from underrepresented backgrounds encounter more challenges than their majority counterparts. The extent of the impact of the COVID-19 pandemic on early-career investigators from underrepresented backgrounds is not yet fully understood. To examine the impact of the pandemic on underrepresented early-career biomedical researchers, this study evaluated differences in productivity, research, and psychological well-being by gender and career status. Method This was a cross-sectional analysis of preintervention data, collected in September–October 2020, from 220 participants enrolled in the Building Up a Diverse Biomedical Research Workforce study. Participants were from 25 academic medical centers in the United States and were underrepresented early-career researchers. The primary outcomes were agreement on a 5-point Likert scale with pandemic impact statements (e.g., “The COVID-19 pandemic has impacted my ability to conduct research”). Thematic analysis was conducted on responses to 2 open-ended questions assessing the pandemic’s impact. Results Most participants were female (79.9%), of non-Hispanic/Latinx/Spanish origin Black/African American (33.2%) or Hispanic/Latinx/Spanish origin (34.1%), and early-career faculty (53.4%). Over half of participants agreed or strongly agreed that the COVID-19 pandemic impacted their ability to work (55.7%) and conduct research (70.7%). Themes from qualitative analysis suggested lower research productivity, concerns about the academic job market and funding, and psychological distress due to the pandemic. Women were more likely to attribute lost productivity and psychological distress to homeschooling and childcare responsibilities. Postdoctoral fellows were concerned about more competition for fewer academic positions. Conclusions In this study of early-career underrepresented biomedical researchers, the impact of the COVID-19 pandemic was widely felt by participants, varying by gender and career status. For those postdoctoral fellows and early-career faculty who are underrepresented, it is critical for institutions to offer flexibility in their positions.

The impact of social unrest due to systemic racism on underrepresented post-doctoral fellows and early-career faculty.

Introduction: Social unrest tied to racism negatively impacted half of NIH-funded extramural researchers underrepresented (UR) in science. UR early-career scientists encounter more challenges in their research careers, but the impact of social unrest due to systemic racism in this group is unclear. We used mixed methods to describe the impact of social unrest due to systemic racism on mentoring relationships, research, and psychological well-being in UR post-doctoral fellows and early-career faculty. Methods: This is a cross-sectional analysis of data collected in September 2021-January 2022 from 144 UR early-career researchers from 25 academic medical centers in the Building Up Trial. The primary outcomes were agreement on five-point Likert scales with social unrest impact statements (e.g., "I experienced psychological distress due to events of social unrest regarding systemic racism"). Thematic analysis was conducted on responses to one open-ended question assessing how social unrest regarding systemic racism affected participants. Results: Most participants were female (80%), non-Hispanic Black (35%), or Hispanic (40%). Over half of participants (57%) experienced psychological distress as a result of social unrest due to systemic racism. Participants described direct and indirect discrimination and isolation from other persons of color at their institutions. Twice as many participants felt their mentoring relationships were positively (21%) versus negatively (11%) impacted by social unrest due to systemic racism. Conclusions: Experiences with racial bias and discrimination impact the career and well-being of UR early-career researchers. Mentoring relationships and institutional support play an important role in buffering the negative impact of racial injustice for this population.

The impact of the COVID-19 pandemic on underrepresented early-career PhD and physician scientists.

Underrepresented minorities have higher attrition from the professoriate and have experienced greater negative impacts of the COVID-19 pandemic. The purpose of this study was to compare the impact of COVID-19 on the lives of 196 early-career physician-scientists versus PhD researchers who are underrepresented in biomedical research. Participants in the Building Up study answered questions on the impact of the COVID-19 pandemic on their personal and professional lives, and a mixed-methods approach was used to conduct the analysis. While most participants experienced increases in overall stress (72% of PhD researchers vs 76% of physician-scientists), physician-scientists reported that increased clinical demands, research delays, and the potential to expose family members to SARS-CoV-2 caused psychological distress, specifically. PhD researchers, more than physician-scientists, reported increased productivity (27% vs 9%), schedule flexibilities (49% vs 25%), and more quality time with friends and family (40% vs 24%). Future studies should consider assessing the effectiveness of programs addressing COVID-19-related challenges experienced by PhD researchers and physician-scientists, particularly those from underrepresented backgrounds.