Author Correction: Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial (Nature Medicine, (2021), 27, 11, (2012-2024), 10.1038/s41591-021-01488-2)

In the version of this Article initially published, there was an omission in the member list for the CONCOR-1 Study Group. Valérie Arsenault (Héma-Québec, Montreal, Quebec, Canada) has now been included in the CONCOR-1 Study Group in the online version of the article

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery.

BACKGROUND The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes. RESULTS The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, -1.11 percentage points; 95% confidence interval [CI], -2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes. CONCLUSIONS In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .)

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Bleeding complications from the direct oral anticoagulants

Abstract Background Direct oral anticoagulants (DOACs) are now standard of care for the management of thromboembolic risk. A prevalent issue of concern is how to manage direct oral anticoagulant (DOAC)-associated bleeding for which there is no specific antidote available for clinical use. We conducted a retrospective case series to describe the Toronto, Canada multicenter experience with bleeding from dabigatran or rivaroxaban. Methods Retrospective chart review of DOAC bleeding necessitating referral to hematology and/or transfusion medicine services at five large University of Toronto affiliated academic hospitals from January 2011 to December 2013. Results Twenty-six patients with DOAC bleeding were reviewed; 42 % bleeds intracranial and 50 %, gastrointestinal. All patients had at least one risk factor associated with DOAC bleeding reported in previous studies. Inconsistent bleed management strategies were evident. Median length of hospital stay was 11 days (1–90). Five thromboembolic events occurred after transfusion based-hemostatic therapy and there were six deaths. Conclusions Management of DOAC bleeding is variable. Clinical trial data regarding DOAC reversal is needed to facilitate optimization and standardization of bleeding treatment algorithms

Decision Analysis in SHared decision making for Thromboprophylaxis during Pregnancy (DASH-TOP) : a sequential explanatory mixed methods pilot study protocol

Decision analysis is a quantitative approach to decision making that could bridge the gap between decisions based solely on evidence and the unique values and preferences of individual patients, a feature especially important when existing evidence cannot support clear recommendations and there is a close balance between harms and benefits for the treatments options under consideration. Low molecular weight heparin (LMWH) for the prevention of venous thromboembolism (VTE) during pregnancy represents one such situation. The objective of this paper is to describe the rationale and methodology of a pilot study that will explore the application of decision analysis to a shared decision-making process involving prophylactic LMWH for pregnant women or those considering pregnancy who have experienced a VTE. We will conduct an international, mixed methods, explanatory, sequential study, including quantitative data collection and analysis followed by qualitative data collection and analysis. In step I, we will ask women who are pregnant or considering pregnancy and have experienced VTE to participate in a shared decision-making intervention for prophylactic LMWH. The intervention consists of three components: a direct choice exercise, a values elicitation exercise and a personalised decision analysis. After administration of the intervention, we will ask women to make a treatment decision and measure decisional conflict, self-efficacy and satisfaction. In step II, which follows the analysis of quantitative data, we will use the results to inform the qualitative interview. Step III will be a qualitative descriptive study that explores participants' experiences and perceptions of the intervention. In step IV, we will integrate findings from the qualitative and quantitative analyses to obtain meta-inferences. Site-specific ethics boards have approved the study. All participants will provide informed consent. The research team will take an integrated approach to knowledge translation

Adverse effects of small-volume red blood cell transfusions in the neonatal population

Abstract Background Adverse transfusion reactions in the neonatal population are poorly understood and defined. The incidence and pattern of adverse effects due to red blood cell (RBC) transfusion are not well known, and there has been no systematic review of published adverse events. RBC transfusions continue to be linked to the development of morbidities unique to neonates, including chronic lung disease, retinopathy of prematurity, intraventricular haemorrhage and necrotising enterocolitis. Uncertainties about the exact nature of risks alongside benefits of RBC transfusion may contribute to evidence of widespread variation in neonatal RBC transfusion practice. Our review aims to describe clinical adverse effects attributed to small-volume (10–20 mL/kg) RBC transfusions and, where possible, their incidence rates in the neonatal population through the systematic identification of all relevant studies. Methods A comprehensive search of the following bibliographic databases will be performed: MEDLINE (PubMed/OVID which includes the Cochrane Library) and EMBASE (OVID). The intervention of interest is small-volume (10–20 mL/kg) RBC transfusions in the neonatal population. We will undertake a narrative synthesis of the evidence. If clinical similarity and data quantity and quality permit, we will also carry out meta-analyses on the listed outcomes. Discussion This systematic review will identify and synthesise the reported adverse effects and associations of RBC transfusions in the neonatal population. We believe that this systematic review is timely and will make a valuable contribution to highlight an existing research gap. Trial Registration PROSPERO, CRD42013005107 http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD4201300510