1.
Early Outpatient Treatment for Covid-19 with Convalescent Plasma
Sullivan DJ, Gebo KA, Shoham S, Bloch EM, Lau B, Shenoy AG, Mosnaim GS, Gniadek TJ, Fukuta Y, Patel B, et al
The New England journal of medicine. 2022
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Editor's Choice
Abstract
BACKGROUND Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).
PICO Summary
Population
Symptomatic adults who tested positive for severe acute respiratory syndrome coronavirus 2, at 23 trial sites in the United States (n= 1,225).
Intervention
Convalescent plasma transfusion (n= 610).
Comparison
Control plasma transfusion (n= 615).
Outcome
Covid-19-related hospitalization within 28 days after transfusion occurred in 17 of 592 patients (2.9%) who received convalescent plasma and 37 of 589 patients (6.3%) who received control plasma, which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated patients could not be inferred. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in patients who were not hospitalized.
2.
Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
Sullivan DJ, Gebo KA, Shoham S, Bloch EM, Lau B, Shenoy AG, Mosnaim GS, Gniadek TJ, Fukuta Y, Patel B, et al
medRxiv : the preprint server for health sciences. 2021
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Free full text
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Editor's Choice
Abstract
BACKGROUND The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain. METHODS This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021. RESULTS A total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions. CONCLUSION Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic. TRIAL REGISTRATION ClinicalTrials.gov number, NCT04373460 .
PICO Summary
Population
SARS-CoV-2 positive adults within 8 days of symptom onset (n= 1,225).
Intervention
High titre convalescent plasma (n= 592).
Comparison
ABO compatible control plasma (n= 589).
Outcome
A total of 1,181 patients were transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) patients who received ABO compatible control plasma and in 17 of 592 (2.9%) patients who received convalescent plasma corresponding to a 54% risk reduction.
3.
Implementation outcomes of policy and programme innovations to prevent obstetric haemorrhage in low- and middle-income countries: a systematic review
Ryan N, Vieira D, Goffman D, Bloch EM, Akaba GO, D'Mello BS, Egekeze C, Snyder A, Lyimo M, Nnodu O, et al
Health policy and planning. 2020
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Editor's Choice
Abstract
Globally, obstetric haemorrhage (OH) remains the leading cause of maternal mortality. Much of the associated mortality is ascribed to challenges surrounding deployment of innovations rather than lack of availability. In low- and middle-income countries (LMICs), where the burden is highest, there is a growing interest in implementation research as a means to bridge the 'know-do' gap between proven interventions and their reliable implementation at scale. In this systematic review, we identified and synthesized qualitative and quantitative data across the implementation outcomes of OH prevention innovations in LMICs using a taxonomy developed by Proctor et al. We also identified service outcomes for the included innovations, as well as implementation strategies and implementation facilitators and barriers. Eligible studies were empirical, focused on the implementation of OH prevention programmes or policies and occurred in an LMIC. Eight databases were searched. Two authors independently assessed studies for selection and extracted data; the first author resolved discrepancies. Narrative synthesis was used to analyse and interpret the findings. Studies were predominantly focused in Africa and on primary prevention. Interventions included prophylactic use of uterotonics (n = 7), clinical provider skills training (n = 4) and provision of clinical guidelines (n = 1); some (n = 3) were also part of a multi-component quality improvement bundle. Various barriers were reported, including challenges among intervention beneficiaries, providers and within the health system; however, studies reported the development and testing of practical implementation solutions. These included training and monitoring of implementers, community and stakeholder engagement and guidance by external mentors. Some studies linked successful delivery to implementation outcomes, most commonly adoption and acceptability, but also feasibility, penetration and sustainability. Findings suggest that innovations to prevent OH can be acceptable, appropriate and feasible in LMIC settings; however, more research is needed to better evaluate these and other under-reported implementation outcomes.
PICO Summary
Population
Women with obstetric haemorrhage (OH) in low and middle-income countries (LMICs).
Intervention
Systematic review to identify and synthesize qualitative and quantitative data across the implementation outcomes of OH prevention innovations in LMICs (12 studies).
Comparison
Outcome
Studies were predominantly focused in Africa and on primary prevention. Interventions included prophylactic use of uterotonics (n= 7), clinical provider skills training (n= 4) and provision of clinical guidelines (n= 1); some (n= 3) were also part of a multi-component quality improvement bundle. Various barriers were reported, including challenges among intervention beneficiaries, providers and within the health system; however, studies reported the development and testing of practical implementation solutions. These included training and monitoring of implementers, community and stakeholder engagement and guidance by external mentors. Some studies linked successful delivery to implementation outcomes, most commonly adoption and acceptability, but also feasibility, penetration and sustainability.