Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1288-3) contains supplementary material, which is available to authorized users.

Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Background Because of the coronavirus disease (COVID-19) pandemic, graduate medical education programs adopted virtual interviews (VIs) as the default modality for the 2020 recruitment season. It is unknown whether VIs allowed applicants to effectively evaluate programs, and the best interview format for the future is unclear. Objective To 1 ) assess pulmonary and critical care applicants’ perceived ability to evaluate programs using VIs, 2 ) determine the attitudes of applicants toward the components of VIs, and 3 ) identify applicants’ preferences for the future fellowship interview format. Methods After the National Residency Matching Program medical subspecialty match, an electronic survey was sent to 1,067 applicants to pulmonary and critical care medicine programs asking them to compare their fellowship VI experience with their residency in-person interview (IPI) experience. Results Three hundred six (29%) applicants responded to the survey, and 289 completed it (27%). There were 117 (40%) women and 146 (51%) White individuals. Most respondents believed that VIs hindered their ability to evaluate programs’ culture, faculty–fellow relationships, location, facilities, and their own fit within the program. They believed they were able to evaluate the clinical experience, curriculum, and potential for academic development equally well compared with IPIs. The most helpful elements of VIs were the interview with the program director, meetings with the fellows, and interviews with faculty members. Less helpful elements included conference access, prerecorded program director presentations, virtual hospital and city tours, and video testimonials. One hundred twenty-three respondents (43%) chose VIs with an optional visit as their preferred future interview format, 85 (29%) chose IPIs, 54 (19%) wanted a choice between VIs and IPIs, and 27 (9%) chose VIs only. Conclusion Most pulmonary and critical care medicine applicants preferred future interviews to include both VIs and the option of an in-person visit or interview. This study can assist programs in designing their future interview formats in a trainee-centric fashion.

OBJECTIVES: To investigate the potential influence of racial differences in outcomes of patients infected by coronavirus disease 2019-positive patients who require intensive care in an urban hospital. DESIGN: Retrospective cohort study. SETTING: Henry Ford Health System Multidisciplinary ICU, a total of 156 beds spread throughout the hospital in Detroit, MI. PATIENTS: We obtained data from the electronic medical record of all adult severe acute respiratory syndrome coronavirus-2-positive patients managed in the ICU of Henry Ford Hospital in Detroit, MI, between March 13, 2020, and July 31, 2020. Included patients were divided into two groups: people of color (including Black, Asian, Hispanic/Latino, and Arab) and White. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 365 patients were evaluated: 219 were Black (60.0%), 129 were White (35.3%), two were Asian (0.6%), eight were Hispanic/Latino (2.2%), and seven were Arab (1.9%). People of color were younger (62.8 vs 67.1; p = 0.007), with equal distribution of sex. People of color had less coronary artery disease (34 [14.4%] vs 35 [27.1%]; p =0.003) and less self-reported use of regular alcohol consumption (50 [21.2%] vs 12 [9.3%]; p = 0.004) than Whites, with no differences in diabetes (125 [53.0%] vs 66 [51.2%]; p = 0.742), hypertension (188 [79.7%] vs 99 [76.8%]; p = 0.516), congestive heart failure (41 [17.4%] vs 32 [24.8%]; p = 0.090), or chronic kidney disease (123 [54.1%] vs 55 [42.6%]; p = 0.083). There was no difference in ICU length of stay between people of color (18 d [CI, 7–47 d]) and Whites (18 d [CI, 6–48 d]; p = 0. 0.979). Neither frequency (72.5% vs 71.3%; p = ns) nor median time to mechanical ventilation between people of color (9 d [CI, 6–15 d]) and Whites (10 d [CI, 5–16 d]; p = 0.733) was different. Overall, 188 patients (51.5 %) died in the hospital. The 28-day mortality was lower in people of color (107/236; 45.3%) versus Whites (73/129; 56.6%) (adjusted odds ratio 0.60; p = 0.034), and there was an increased median survival time in people of color (20 d) versus Whites (13.5 d; hazard ratio 0.62; p = 0.002). The inhospital mortality was lower in people of color versus White, but the difference was not statistically significant (113 [47.9%] vs 75 [58.1%], respectively; p = 0.061). Finally, there was no significant difference in days of symptoms prior to admission, frequency of presenting symptoms, or frequency or severity of acute respiratory distress syndrome between the two groups. CONCLUSIONS: In critically ill patients infected with coronavirus disease 2019, people of color had a lower 28-day mortality than Whites with no difference in hospital mortality, ICU length of stay, or rates of intubation. These findings are contrary to previously held beliefs surrounding the pandemic.