The Emergence of Population Health in US Academic Medicine

Importance In response to rapidly growing interest in population health, academic medical centers are launching department-level initiatives that focus on this evolving discipline. This trend, with its potential to extend the scope of academic medicine, has not been well characterized. Objective To describe the emergence of departments of population health at academic medical centers in the United States, including shared areas of focus, opportunities, and challenges. Design, Setting, and Participants This qualitative study was based on a structured in-person convening of a working group of chairs of population health–oriented departments on November 13 and 14, 2017, complemented by a survey of core characteristics of these and additional departments identified through web-based review of US academic medical centers. United States medical school departments with the word population in their name were included. Centers, institutes, and schools were not included. Main Outcomes and Measures Departments were characterized by year of origin, areas of focus, organizational structure, faculty size, teaching programs, and service engagement. Opportunities and challenges faced by these emerging departments were grouped thematically and described. Results Eight of 9 population health–oriented departments in the working group were launched in the last 6 years. The 9 departments had 5 to 97 full-time faculty. Despite varied organizational structures, all addressed essential areas of focus spanning the missions of research, education, and service. Departments varied significantly in their relationships with the delivery of clinical care, but all engaged in practice-based and/or community collaboration. Common attributes include core attention to population health–oriented research methods across disciplines, emphasis on applied research in frontline settings, strong commitment to partnership, interest in engaging other sectors, and focus on improving health equity. Tensions included defining boundaries with other academic units with overlapping areas of focus, identifying sources of sustainable extramural funding, and facilitating the interface between research and health system operations. Conclusions and Relevance Departments addressing population health are emerging rapidly in academic medical centers. In supporting this new framing, academic medicine affirms and strengthens its commitment to advancing population health and health equity, to improving the quality and effectiveness of care, and to upholding the social mission of medicine

Posttransplant survival is not diminished in heart transplant recipients bridged with implantable left ventricular assist devices

BackgroundThe purpose of this study was to compare posttransplantation morbidity and mortality in orthotopic heart transplant recipients bridged to transplant with a left ventricular assist device with nonbridged recipients. To account for potential differences across device types, we stratified bridge-to-transplant recipients by type of ventricular assist device: extracorporeal (EXTRA), paracorporeal (PARA), and intracorporeal (INTRA).MethodsThe United Network for Organ Sharing provided de-identified patient-level data. The study population included 10,668 orthotopic heart transplant recipients aged 18 years old or older and undergoing transplantation between January 1, 2001, and December 31, 2006. Follow-up data were provided through August 3, 2008, with a mean follow-up time of 3.17 ± 2.15 years (range, 0–8.11 years). The primary outcome was actuarial posttransplant graft survival. Other outcomes of interest included infection, stroke, and dialysis during the transplant hospitalization; primary graft failure at 30 days; transplant hospitalization length of stay; and long-term complications including diabetes mellitus, transplant coronary artery disease, and chronic dialysis. Multivariable Cox proportional hazards regression (backward, P < .15) was used to determine the relationship between groups and overall graft survival, and multivariable logistic regression analysis (backward, P < .15) was used to determine the relationship between groups and secondary outcome measures.ResultsIn multivariable Cox regression analysis, when compared with the nonbridged group, risk-adjusted greater than 90-day graft survival was diminished among the EXTRA group (hazard ratio = 3.54, 2.28–5.51, P < .001), but not the INTRA group (1.04, 0.719–1.51, P = .834) or the PARA group (1.06, 0.642–1.76, P = .809). There were no significant differences in risk-adjusted graft survival across the 4 groups during the 90-days to 1-year or 1- to 5-year intervals. However, at more than 5 years, risk-adjusted graft survival in the INTRA group (0.389, 0.205–0.738, P = .004) was better than in the nonbridged group. The EXTRA, PARA, and INTRA groups all experienced increased risks of infection. The EXTRA group had increased risks of dialysis, stroke, and primary graft failure at 30 days, whereas neither the PARA nor the INTRA group differed from the nonbridged group. Long-term complications did not differ by group.ConclusionThe use of implantable left ventricular assist devices as bridges to transplantation, including both intracorporeal and paracorporeal devices, is not associated with diminished posttransplant survival. However, 90-day survival was diminished in recipients bridged with extracorporeal devices

Designing comparative effectiveness trials of surgical ablation for atrial fibrillation: Experience of the Cardiothoracic Surgical Trials Network

ObjectiveSince the introduction of the cut-and-sew Cox maze procedure for atrial fibrillation, there has been substantial innovation in techniques for ablation. Use of alternative energy sources for ablation simplified the procedure and has resulted in dramatic increase in the number of patients with atrial fibrillation treated by surgical ablation. Despite its increasingly widespread adoption, there is lack of rigorous clinical evidence to establish this procedure as an effective clinical therapy.MethodsThis article describes a comparative effectiveness randomized trial, supported by the Cardiothoracic Surgical Clinical Trials Network, of surgical ablation with left atrial appendage closure versus left atrial appendage closure alone in patients with persistent and long-standing persistent atrial fibrillation undergoing mitral valve surgery. Nested within this trial is a further randomized comparison of 2 different lesions sets: pulmonary vein isolation and the full maze lesion set.ResultsThis article addresses trial design challenges, including how best to characterize the target population, operationalize freedom from atrial fibrillation as a primary end point, account for the impact of antiarrhythmic drugs, and measure and analyze secondary end points, such as postoperative atrial fibrillation load.ConclusionsThis article concludes by discussing how insights that emerge from this trial may affect surgical practice and guide future research in this area

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. FUNDING: US National Institutes of Health and Operation Warp Speed