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The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm--relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care. A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes., Author(s): Philippe Bégin [sup.1] [sup.2] , Jeannie Callum [sup.3] [sup.4] [sup.5] [sup.6] , Erin Jamula [sup.7] , Richard Cook [sup.8] , Nancy M. Heddle [sup.6] [sup.7] [sup.9] , Alan Tinmouth [...]

Background: Bleeding is a primary outcome for many transfusion‐related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi‐step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients. Study Design and Methods: Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used. Results: HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding. Discussion: Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients. [ABSTRACT FROM AUTHOR]

Background: Hospital transfusion services order blood products to satisfy orders and maintain inventory levels during unexpected periods of increased blood demand. Surplus inventory may outdate before being allocated to a recipient. Blood product outdating is the largest contributor to blood wastage. Study Design: A province‐wide redistribution program was designed and implemented to redistribute near‐outdate plasma protein and related blood products from low‐usage to high‐usage hospitals. Program operations and details are described in this paper. Two transport container configurations were designed and validated for transport of all blood products. A cost‐analysis was performed to determine the effectiveness of this redistribution program. Results: A total of 130 hospital transfusion services contributed at least one near‐outdate blood product for redistribution between January 2012 and March 2020. These services redistributed 15,499 products through 3412 shipments, preventing the outdating of $17,570,700 CAD worth of product. Program costs were $14,900 for shipping and $30,000 for staffing. Failed time limits or non‐compliance with packing configurations resulted in $388,200 worth of blood products (97 shipments containing 816 products) being discarded. Courier transport delays was the most common reason (42/97; 43%) for transport failure. Conclusion: Redistributing near‐outdate blood products between hospitals is a feasible solution to minimize outdating. Despite heterogeneity of Canadian blood product inventory, all products (each with unique storage and transport requirements) were successfully redistributed in one of two validated and simple containers. Total operation costs of this program were small in comparison to the $17.6 million in savings associated with preventing the discard of outdated products. [ABSTRACT FROM AUTHOR]

Background: Mortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting. Methods: An open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality. Results: There were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1–3) unit and 2 (IQR, 1–3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1–10) and was 6.2% (95% CI, 3.2–12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86–0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00–0.31, p < 0.01) were associated with reduced 30-day mortality. Conclusions: The study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed. Trial registration: Pan African Clinical Trial Registry, (PACTR202302787440132). Registered on 06/02/2023. [ABSTRACT FROM AUTHOR]

Background: The CONvalescent Plasma for Hospitalized Adults With COVID‐19 Respiratory Illness (CONCOR‐1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID‐19 patients. This study evaluates the cost‐effectiveness of convalescent plasma and its impact on quality‐of‐life to provide insight into its potential as an alternative treatment in resource‐constrained settings. Methods: Individual patient data on health outcomes and resource utilization from the CONCOR‐1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post‐randomization. Baseline and 30‐day EQ‐5D‐5L were measured to calculate quality‐adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ‐5D‐5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ‐5D‐5L scores from the same population but only uses costs from this population. Results: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ‐5D‐5L scores were 0.61 in both arms (p =.85) at baseline. At 30 days, EQ‐5D‐5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p =.46). The incremental cost was $4458 and the incremental quality‐adjusted life day was −0.078. Discussion: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID‐19. [ABSTRACT FROM AUTHOR]

Background: Managing Canada's immunoglobulin (Ig) product resource allocation is challenging due to increasing demand, high expenditure, and global shortages. Detection of groups with high utilization rates can help with resource planning for Ig products. This study aims to uncover utilization subgroups among the Ig recipients using electronic health records (EHRs). Methods: The study included all Ig recipients (intravenous or subcutaneous) in Calgary from 2014 to 2020, and their EHR data, including blood inventory, recipient demographics, and laboratory test results, were analyzed. Patient clusters were derived based on patient characteristics and laboratory test data using K‐means clustering. Clusters were interpreted using descriptive analyses and visualization techniques. Results: Among 4112 recipients, six clusters were identified. Clusters 1 and 2 comprised 408 (9.9%) and 1272 (30.9%) patients, respectively, contributing to 62.2% and 27.1% of total Ig utilization. Cluster 3 included 1253 (30.5%) patients, with 86.4% of infusions administered in an inpatient setting. Cluster 4, comprising 1034 (25.1%) patients, had a median age of 4 years, while clusters 2–6 were adults with median ages of 46–60. Cluster 5 had 62 (1.5%) patients, with 77.3% infusions occurring in emergency departments. Cluster 6 contained 83 (2.0%) patients receiving subcutaneous Ig treatments. Conclusion: The results identified data‐driven segmentations of patients with high Ig utilization rates and patients with high risk for short‐term inpatient use. Our report is the first on EHR data‐driven clustering of Ig utilization patterns. The findings hold the potential to inform demand forecasting and resource allocation decisions during shortages of Ig products. [ABSTRACT FROM AUTHOR]

Epidemics are a serious public health threat, and the resources for mitigating their effects are typically limited. Decision-makers face challenges in forecasting the supply and demand for these resources as prior information about the disease is often not available, the behaviour of the disease can periodically change (either naturally or as a result of public health policies) and can differ by geographical region. In this work, we discuss a model that is suitable for short-term real-time supply and demand forecasting during emerging outbreaks. We consider a case study of demand forecasting and allocating scarce quantities of COVID-19 Convalescent Plasma (CCP) in an international multi-site Randomized Controlled Trial (RCT) involving multiple hospital hubs across Canada (excluding Québec). We propose a data-driven mixed-integer programming (MIP) resource allocation model that assigns available resources to maximize a notion of fairness among the resource-demanding entities. Numerical results from applying our MIP model to the case study suggest that our approach can help balance the supply and demand of limited products such as CCP and minimize the unmet demand ratios of the demand entities. We analyse the sensitivity of our model to different allocation settings and show that our model assigns equitable allocations across the entities. [ABSTRACT FROM AUTHOR]

The article "Meta-analysis of efficacy and safety of pathogen-reduced platelet components: Request for clarification" discusses a meta-analysis conducted on trials studying the efficacy and safety of pathogen-reduced platelet concentrates in patients with chemotherapy-induced thrombocytopenia. The authors analyzed the effectiveness of Intercept and Mirasol PC in preventing bleeding compared to standard platelets, with separate analyses for each pathogen inactivation approach. The letter to the editor requests clarification on the rationale for the two-subgroup analysis, differences in trial data compared to a Cochrane review, and errors in data abstraction from the Mirasol Clinical Evaluation Trial. The authors also address the importance of protocol registration for transparency in meta-analyses. [Extracted from the article]

Background: Anti‐K is an alloantibody stimulated in response to the KEL1 antigen and may cause hemolytic disease of the fetus and newborn (HDFN). Provision of KEL1 negative blood to females of child‐bearing potential was not our practice. We assessed the impact of our policy and assessed feasibility of a KEL1 negative transfusion policy. Study design and methods: This is a cohort study spanning Jan 1, 2007–Jun 30, 2017 in Hamilton, Canada. Data were obtained via our institution's transfusion database. Chart reviews of females age ≤45 with anti‐K were performed; data on RBC KEL1 phenotype were obtained from the blood supplier when needed to ascertain the cause of alloimmunization. Descriptive analysis of hospital KEL1 negative inventory demand and supply was performed. Results: From Jan 2007‐Jun 2017, 8.6% of all RBC units transfused were provided to females age ≤45. There were 111 females with detectable anti‐K. Median age at time of antibody detection was 34 years (interquartile range 27–40) and 28 of 111 (25.2%) patients may have been alloimmunized by transfusion. Of 49 pregnancies, seven had complications due to anti‐K. We estimated that our existing RBC inventory (with 16% units known to be KEL1 negative in 2017) is sufficient to meet demand and support a KEL1 negative transfusion policy for females age ≤45. Conclusion: Transfusion was responsible for alloimmunization in 25% of females with anti‐K over 10 years. Analysis of supply and demand can be used to inform feasibility of a KEL1 negative transfusion policy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Abundant clinical evidence supports the safety of red blood cell (RBC) concentrates for transfusion irrespective of storage age, but still, less is known about how recipient characteristics may affect post‐transfusion RBC recovery and function. Septic patients are frequently transfused. We hypothesized that the recipient environment in patients with septicaemia would blunt the increase in post‐transfusion blood haemoglobin (Hb). The main objective was to compare the post‐transfusion Hb increment in hospitalized patients with or without a positive blood culture. Materials and Methods: A retrospective cohort study using data from the Transfusion Research, Utilization, Surveillance, and Tracking database (TRUST) was performed. All adult non‐trauma in‐patients transfused between 2010 and 2017 with ≥1 RBC unit, and for whom both pre‐ and post‐transfusion complete blood count and pre‐transfusion blood culture data were available were included. A general linear model with binary blood culture positivity was fit for continuous Hb increment after transfusion and was adjusted for patient demographic parameters and transfusion‐related covariates. Results: Among 210,263 admitted patients, 6252 were transfused: 596 had positive cultures, and 5656 had negative blood cultures. A modelled Hb deficit of 1.50 g/L in blood culture‐positive patients was found. All covariates had a significant effect on Hb increment, except for the age of the transfused RBC. Conclusion: Recipient blood culture positivity was associated with a statistically significant but modestly lower post‐transfusion Hb increment in hospitalized patients. In isolation, the effect is unlikely to be clinically significant, but it could become so in combination with other recipient characteristics. [ABSTRACT FROM AUTHOR]

Background: The demand and supply of blood are highly variable over time. Blood inventory management that relies heavily on experience‐based decisions may not be adaptive to real demand, leading to high operational costs, wastage, and shortages. Methods: We combined statistical modeling, machine learning, and optimization methods to develop a data‐driven demand forecasting and inventory management strategy for red blood cells (RBCs). We then used the strategy to inform daily blood orders. A secondary semi‐weekly (twice per week) ordering strategy was developed to handle the last‐mile split delivery problem for blood suppliers, characterized by multi‐deliveries to the same location multiple times during a short period of time. Both strategies were evaluated using the TRUST database including all patient data across four hospitals in Hamilton, Ontario. Results: We identified 227,944 RBC transfusions for 40,787 patients in Hamilton, Ontario from 2012 to 2018. The predicted daily demand from the hybrid demand forecasting model was not significantly different from the actual daily demand (paired t‐test p‐value = 0.163); however, the proposed daily ordering quantity from the model was significantly lower than the actual ordering quantity (p‐value <0.001). The proposed daily ordering strategy reduced inventory levels by 38.4% without risk of shortages, leading to an overall cost reduction of 43.0% (95% confidence interval [CI]: 42.3%, 43.7%) compared with the actual cost. The semi‐weekly ordering strategy reduced ordering frequency by 62.6% (95% CI: 61.5%, 63.7%). Conclusion: The proposed data‐driven ordering strategy combining demand forecasting and inventory optimization can achieve significant cost savings for healthcare systems and blood suppliers. [ABSTRACT FROM AUTHOR]

Background: The relationship between ABO non‐identical transfusion and the outcomes of necrotizing enterocolitis (NEC), and all‐cause mortality in very‐low birth weight (VLBW) neonates receiving red blood cell transfusion is unknown. Study design and methods: A retrospective multicenter cohort study was conducted in VLBW neonates in neonatal intensive care units between 2004 and 2016. VLBW (≤1500 grams) neonates were followed until discharge or in‐hospital death. The primary exposure was ABO group. Secondary exposures included platelet count, plasma transfusions, and maternal ABO group. Outcome measures were NEC (defined as Bell stage ≥ 2) and all‐cause mortality. Time‐dependent Cox regression models with competing risks were used to investigate factors associated with NEC and mortality. Results: Thousand and sixteen neonates were included with 10.8% developing NEC (n = 110) and 14.1% mortality (n = 143). Platelet count (hazard ratio [HR] = 0.995; 95% confidence interval [CI]: 0.922–0.998) and number of plasma transfusions (HR = 2.908; 95% CI:1.265–6.682) were associated with NEC, while ABO group (non‐O vs. O) was not (HR = 0.761; 95% CI: 0.393–1.471). Higher all‐cause mortality occurred in neonates without NEC who were non‐O compared with O (HR = 17.5; 95% CI: 1.784–171.692), but not in neonates with NEC (HR = 1.112; 95% CI: 0.142–8.841). Plasma transfusion was associated with increased mortality in both groups. Discussion: ABO non‐identical transfusion was not associated with NEC or mortality in neonates with NEC. It was associated with increased mortality in neonates without NEC. As many neonatal intensive care units transfuse only O group blood as routine practice, future trials are needed to investigate the association between this practice and neonatal mortality. [ABSTRACT FROM AUTHOR]