Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19.

BACKGROUNDEvidence supporting convalescent plasma (CP), one of the first investigational treatments for coronavirus disease 2019 (COVID-19), has been inconclusive, leading to conflicting recommendations. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19.METHODSThe multicenter, electronic health records-based, retrospective study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare-affiliated community hospitals. Coarsened exact matching (1:k) was employed, resulting in a sample of 3774 CP and 10,687 comparison patients.RESULTSExamination of mortality using a shared frailty model, controlling for concomitant medications, date of admission, and days from admission to transfusion, demonstrated a significant association of CP with lower mortality risk relative to the comparison group (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.59-0.86; P < 0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our real-time risk model (RTRM), indicated that patients who received CP recovered more quickly. The stratification of days to transfusion revealed that CP within 3 days after admission, but not within 4 to 7 days, was associated with a significantly lower mortality risk (aHR = 0.53; 95% CI, 0.47-0.60; P < 0.001). CP serology level was inversely associated with mortality when controlling for its interaction with days to transfusion (HR = 0.998; 95% CI, 0.997-0.999; P = 0.013), yet it did not reach univariable significance.CONCLUSIONSThis large, diverse, multicenter cohort study demonstrated that CP, compared with matched controls, is significantly associated with reduced risk of in-hospital mortality. These observations highlight the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19.FUNDINGThis research was supported in whole by HCA Healthcare and/or an HCA Healthcare-affiliated entity, including Sarah Cannon and Genospace.

Outcomes of COVID-19 in hospitalized solid organ transplant recipients compared to a matched cohort of non-transplant patients at a national healthcare system in the United States.

Data describing outcomes of solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) are variable, and the association between SOT status and mortality remains unclear. In this study, we compare clinical outcomes of SOT recipients hospitalized with COVID-19 between March 10, and September 1, 2020, to a matched cohort of non-SOT recipients at a national healthcare system in the United States (US). From a population of 43 461 hospitalized COVID-19-positive patients, we created a coarsened exact matched cohort of 4035 patients including 128 SOT recipients and 3907 weighted matched non-SOT controls. Multiple logistic regression was used to evaluate association between SOT status and clinical outcomes. Among the 4035 patients, median age was 60 years, 61.7% were male, 21.9% were Black/African American, and 50.8% identified as Hispanic/Latino ethnicity. Patients with a history of SOT were more likely to die within the study period when compared to matched non-SOT recipients (21.9% and 14.9%, respectively; odds ratio [OR] 1.93; 95% confidence interval [CI]: 1.18-3.15). Moreover, SOT status was associated with increased odds of receiving invasive mechanical ventilation (OR [95% CI]: 2.34 [1.51-3.65]), developing acute kidney injury (OR [95% CI]: 2.41 [1.59-3.65]), and receiving vasopressor support during hospitalization (OR [95% CI]: 2.14 [1.31-3.48]).

The critical need for academic health centers to assess the training, support, and career development requirements of clinical research coordinators: recommendations from the Clinical and Translational Science Award Research Coordinator Taskforce.

Clinical Research Coordinators (CRCs) are a vital component of the clinical research enterprise providing a pivotal role in human subject protection through the numerous activities and responsibilities assigned to them. In 2006, the National Institutes of Health's National Center for Research resources (NCRR) implemented the Clinical and Translational Science Awards program (CTSA) to advance biomedical research. As a part of this endeavor, many workgroups were formed among the Consortium to support translational research. The Research Coordinator Taskforce was created as part of the Regulatory Knowledge group of the Clinical Research Innovation Key Function Committee, and focuses on enhancing CTSA capabilities to provide support and training for CRCs. In the spring of 2008, this taskforce conducted two surveys of the then 24 CTSA Consortium members to better understand the current expectations and responsibilities of research coordinators in addition to the mechanism for providing education, training, and support in order for CRCs to successfully meet the study responsibilities placed upon them. The results of these surveys are summarized in this article and provide context to the recommendations of the Research Coordinator Taskforce for institutional considerations, approaches, and best practices for providing education, training, and support the expanding role of CRCs in fulfilling their responsibilities delegated to them by investigators.

Support for investigator-initiated clinical research involving investigational drugs or devices: the Clinical and Translational Science Award experience.

PURPOSE: Investigator-initiated research involving investigational drugs and devices is key to improving health. However, this requires the investigator to serve as a "sponsor-investigator," which can be complex and overwhelming. The Investigational New Drug/Investigational Device Exemption (IND/IDE) Taskforce of the Clinical and Translational Science Award (CTSA) consortium carried out a survey to examine how academic health centers (AHCs) assist sponsor-investigators with regulatory responsibilities. METHOD: The 24 CTSA centers existing in 2008 were surveyed regarding regulatory oversight and support for sponsor-investigators. Responses were analyzed by descriptive statistics. The evaluation of survey responses yielded three models of institutional support/oversight. RESULTS: Nineteen centers and one affiliate responded. Eleven (55%) reported having an IND/IDE support office, increased from five (25%) prior to their CTSA award. The volume of investigator-initiated IND/IDE research was highly variable (measured by numbers of investigators, IND/IDE applications, and studies). Oversight, if done, was provided by either the IND/IDE office or elsewhere in the institution. Most IND/IDE offices assisted with IND/IDE submissions and preparation for external audits. Half reported advanced training for sponsor-investigators. Almost all reported a goal to increase IND/IDE research. Important issues include the need for robust training of investigator/staff, appropriate determination of IND-exempt research, and sufficient support for preparing IND/IDE applications. CONCLUSIONS: Investigator-initiated research involving IND/IDEs is essential, but complex. AHCs should examine how they support sponsor-investigators in meeting the complex requirements. A model of either expert consultation/support or full service will minimize risks to participants and institutions, and regulatory noncompliance.