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Patients with cancer experience higher rates of preventable harm from hospital-acquired bloodstream infections (haBSIs) and central-line-associated bloodstream infections (CLABSIs) compared with the general hospital population. The prevention of haBSIs and CLABSIs in patients with cancer is an urgent priority, and requires standardized surveillance and reporting efforts. The application of haBSI and CLABSI definitions, classification systems and surveillance strategies for patients with cancer is complex, and there is wide variation in clinical practice. Existing systems were not designed explicitly for patients with cancer, and have different strengths and weaknesses in the cancer setting. For these reasons, epidemiological estimates of haBSIs and CLABSIs in patients with cancer also require careful interpretation. This complexity can be a barrier to identifying appropriate targets for intervention and reducing preventable harm. This review provides an overview of key concepts and challenges in haBSI surveillance and prevention specific to patients with cancer. In addition, this review summarizes the strengths and weaknesses of commonly used surveillance definitions and denominators in the setting of cancer care; existing surveillance practice; epidemiology of haBSIs and CLABSIs; prevention strategies; and current knowledge gaps. A global collaborative effort to harmonize the surveillance of hospital-acquired infections in patients with cancer would be invaluable to improve the accuracy and utility of existing data, advance efforts to prevent hospital-acquired infections, and improve patient safety.

Anemia is common in Myelodysplastic Syndromes (MDS). Different anemia treatments have been tested in clinical studies, but the full impact on patients' health-related quality of life (HRQoL) and physical function is unknown. The main aim of this review was to assess whether improvements in anemia are associated with changes in HRQoL/physical function. Twenty-six full-text publications were identified, enrolling 2211 patients: nine randomized trials (RCTs), fourteen non-randomized studies of interventions and three cross-sectional studies. Interventions included: growth factors/erythropoiesis-stimulating agents (n = 14), red cell transfusion (n = 9), erythroid maturation agents (n = 1), or a combination (n = 2). Five RCTs reported no changes in HRQoL despite erythroid response to the intervention, raising the question of whether anemia treatment alone can effectively improve HRQoL. Many studies were considered at high risk of bias for assessing HRQoL. There is a pressing need for future clinical trials to better define the nature of the relationship between anemia and HRQoL/functional outcomes.

Item does not contain fulltext, IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06

Item does not contain fulltext, IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06

Item does not contain fulltext, IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital surv

Background: During extracorporeal life support (ECLS), bleeding is one of the most frequent complications, associated with high morbidity and increased mortality, despite continuous improvements in devices and patient care. Risk factors for bleeding complications in veno-venous (V-V) ECLS applied for respiratory support have been poorly investigated. We aim to develop and internally validate a prediction model to calculate the risk for bleeding complications in adult patients receiving V-V ECLS support. Method(s): Data from adult patients reported to the extracorporeal life support organization (ELSO) registry between the years 2010 and 2020 were analyzed. The primary outcome was bleeding complications recorded during V-V ECLS. Multivariable logistic regression with backward stepwise elimination was used to develop the predictive model. The performance of the model was tested by discriminative ability and calibration with receiver operating characteristic curves and visual inspection of the calibration plot. Result(s): In total, 18 658 adult patients were included, of which 3 933 (21.1%) developed bleeding complications. The prediction model showed a prediction of bleeding complications with an AUC of 0.63. Pre-ECLS arrest, surgical cannulation, lactate, pO2, HCO3, ventilation rate, mean airway pressure, pre-ECLS cardiopulmonary bypass or renal replacement therapy, pre-ECLS surgical interventions, and different types of diagnosis were included in the prediction model. Conclusion(s): The model is based on the largest cohort of V-V ECLS patients and reveals the most favorable predictive value addressing bleeding events given the predictors that are feasible and when compared to the current literature. This model will help identify patients at risk of bleeding complications, and decision making in terms of anticoagulation and hemostatic management.Copyright © 2021 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation

Background: During extracorporeal life support (ECLS), bleeding is one of the most frequent complications, associated with high morbidity and increased mortality, despite continuous improvements in devices and patient care. Risk factors for bleeding complications in veno-venous (V-V) ECLS applied for respiratory support have been poorly investigated. We aim to develop and internally validate a prediction model to calculate the risk for bleeding complications in adult patients receiving V-V ECLS support. Method(s): Data from adult patients reported to the extracorporeal life support organization (ELSO) registry between the years 2010 and 2020 were analyzed. The primary outcome was bleeding complications recorded during V-V ECLS. Multivariable logistic regression with backward stepwise elimination was used to develop the predictive model. The performance of the model was tested by discriminative ability and calibration with receiver operating characteristic curves and visual inspection of the calibration plot. Result(s): In total, 18 658 adult patients were included, of which 3 933 (21.1%) developed bleeding complications. The prediction model showed a prediction of bleeding complications with an AUC of 0.63. Pre-ECLS arrest, surgical cannulation, lactate, pO2, HCO3, ventilation rate, mean airway pressure, pre-ECLS cardiopulmonary bypass or renal replacement therapy, pre-ECLS surgical interventions, and different types of diagnosis were included in the prediction model. Conclusion(s): The model is based on the largest cohort of V-V ECLS patients and reveals the most favorable predictive value addressing bleeding events given the predictors that are feasible and when compared to the current literature. This model will help identify patients at risk of bleeding complications, and decision making in terms of anticoagulation and hemostatic management.Copyright © 2021 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective(s): To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participant(s): In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Intervention(s): Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from-1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Result(s): The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespe

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective(s): To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participant(s): In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Intervention(s): Patients were randomized to receive either open-label aspirin (n=565), a P2Y12 inhibitor (n=455), or no antiplatelet therapy (control; n=529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Result(s): The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecifie

Item does not contain fulltext, IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified c

Acquired hypogammaglobulinemia is common in chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). No previous systematic reviews (SR) have compared different approaches to infection prevention. We aimed to assess the efficacy and safety of prophylactic immunoglobulin (Ig), antibiotics and vaccinations in these patients. We performed a SR and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of prophylactic Ig, antibiotics and vaccinations in adult patients with hematological malignancies commonly associated with acquired hypogammaglobulinemia, specifically CLL, NHL and MM. We searched Pubmed (MEDLINE), EMBASE and Cochrane Registry to 01/09/2021. Results for dichotomous data were expressed as relative risks (RR) with 95% confidence intervals (CI) and pooled using a random effects model. This review was registered with PROSPERO CRD42017070825. From 10,576 studies screened, there were 21 completed and one ongoing RCT. Of these, eight evaluated prophylactic Ig (n=370, seven published before 2000); five evaluated prophylactic antibiotics (n=1587), seven evaluated vaccinations (n=3996) and one compared Ig to antibiotics (n=60). Prophylactic Ig reduced the risk of clinically documented infections (CDIs) by 28%, (n=2 trials; RR 0.72 [95% CI 0.54-0.96]) and vaccinations reduced risk of CDIs by 63%, RR 0.37 (95% CI 0.30-0.45). Prophylactic antibiotics did not reduce the risk of CDIs. No interventions reduced all-cause mortality. Prophylactic Ig and antibiotics increased risk of adverse events. Findings should be interpreted with caution given high risk of bias in many studies. There is a clear need for high-quality contemporary trials to establish the effectiveness of different approaches to prevent infections.Copyright © 2022 American Society of Hematology.

Item does not contain fulltext, IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified c

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%–30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial commenced enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious disease syndromes.

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%-30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial commenced enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious disease syndromes.

The search for clinically effective antivirals against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is ongoing. Repurposing of drugs licensed for non-coronavirus disease 2019 (COVID-19) indications has been extensively investigated in laboratory models and in clinical studies with mixed results. Nafamostat mesylate (nafamostat) is a drug licensed in Japan and Korea for indications including acute pancreatitis and disseminated intravascular coagulation. It is available only for continuous intravenous infusion. In vitro human lung cell line studies with nafamostat demonstrate high antiviral potency against SARS-CoV-2 (half maximal inhibitory concentration [IC50] of 0.0022 µM [compared to remdesivir 1.3 µM]), ostensibly via inhibition of the cellular enzyme transmembrane protease serine 2 (TMPRSS2) preventing viral entry into human cells. In addition, the established antithrombotic activity is hypothesised to be advantageous given thrombosis-associated sequelae of COVID-19. Clinical reports to date are limited, but indicate a potential benefit of nafamostat in patients with moderate to severe COVID-19. In this review, we will explore the pre-clinical, pharmacokinetic and clinical outcome data presently available for nafamostat as a treatment for COVID-19. The recruitment to ongoing clinical trials is a priority to provide more robust data on the safety and efficacy of nafamostat as a treatment for COVID-19.

The frequency and causes of early mortality in patients with newly diagnosed multiple myeloma (NDMM) have not been well described in the era of novel agents. We investigated early mortality in a prospective cohort study of all patients with NDMM registered on the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) at 36 institutions between July 2011 and March 2020. Early mortality was defined as death from any cause within the first 12 months after diagnosis. A total of 2377 patients with NDMM were included in the analysis, with a median (interquartile range) age of 67.4 (58.9-74.60 years, and 60% were male. Overall, 216 (9.1%) patients died within 12 months, with 119 (4.5%) having died within 6 months. Variables that were independent predictors of early mortality after adjustment in multivariable regression included age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.05-1.08; p < 0.001), Eastern Cooperative Oncology Group performance status (OR 1.50, 95% CI 1.26-1.79; p < 0.001), serum albumin (OR 0.95, 95% CI 0.93-0.98; p < 0.001), cardiac disease (OR 1.96, 95% CI 1.35-2.86; p < 0.001) and International Staging System (OR 1.40, 95% CI 1.07-1.82; p = 0.01). For those with a primary cause of death available, it was reported as disease-related in 151 (78%), infection 13 (7%), other 29 (15%). Infection was listed as a contributing factor for death in 38% of patients.

INTRODUCTION: Cryopreservation at -80°C in dimethylsulphoxide extends platelet shelf-life from 7 days to 2 years. Only limited comparative trial data supports the safety and effectiveness of cryopreserved platelets as a treatment for surgical bleeding. Cryopreserved platelets are not currently registered for civilian use in most countries. METHODS AND ANALYSIS: CLIP-II and CLIPNZ-II are harmonised, blinded, multicentre, randomised, controlled clinical non-inferiority trials comparing bleeding, transfusion, safety and cost outcomes associated with cryopreserved platelets versus conventional liquid platelets as treatment for bleeding in cardiac surgery. CLIP-II is planning to enrol patients in 12 tertiary hospitals in Australia; CLIPNZ-II will recruit in five tertiary hospitals in New Zealand. The trials use near-identical protocols aside from details of cryopreserved platelet preparation. Patients identified preoperatively as being at high risk of requiring a platelet transfusion receive up to three units of study platelets if their treating doctor considers platelet transfusion is indicated. The primary endpoint is blood loss through the surgical drains in the 24 hours following intensive care unit (ICU) admission after surgery. Other endpoints are blood loss at other time points, potential complications, adverse reactions, transfusion and fluid requirement, requirement for procoagulant treatments, time to commencement of postoperative anticoagulants, delay between platelet order and commencement of infusion, need for reoperation, laboratory and point-of-care clotting indices, cost, length of mechanical ventilation, ICU and hospital stay, and mortality. Transfusing 202 (CLIP-II) or 228 (CLIPNZ-II) patients with study platelets will provide 90% power to exclude the possibility of greater than 20% inferiority in the primary endpoint. If cryopreserved platelets are not inferior to liquid-stored platelets, the advantages of longer shelf-life would justify rapid change i

BACKGROUND: SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have limited the utility of traditional approaches to randomised controlled trials. METHODS: ASCOT ADAPT is an international, investigator-initiated, adaptive platform, randomised controlled trial of therapeutics for non-critically ill patients hospitalised with COVID-19. The study design is open label and pragmatic. Potential participants are hospitalised adults with PCR confirmed, symptomatic, SARS-CoV-2 infection, within 14 days of symptom onset. Domains include antiviral, antibody and anticoagulant interventions, with a composite primary outcome of 28-day mortality or progression to intensive-care level respiratory or haemodynamic support. Initial interventions include intravenous nafamostat and variable dose anticoagulation. A range of secondary endpoints, and substudies for specific domains and interventions are outlined. DISCUSSION: This paper presents the trial protocol and management structure, including international governance, remote site monitoring and biobanking activities and provides commentary on ethical and pragmatic considerations in establishing the ASCOT ADAPT trial under pandemic conditions. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12620000445976) and ClinicalTrials.gov (NCT04483960).

Item does not contain fulltext, BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulati

Item does not contain fulltext, BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagul

To date, 18 living recommendations for the clinical care of pregnant and postpartum women with COVID-19 have been issued by the National COVID-19 Clinical Evidence Taskforce. This includes recommendations on mode of birth, delayed umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, antenatal corticosteroids, angiotensin-converting enzyme inhibitors, disease-modifying treatments (including dexamethasone, remdesivir and hydroxychloroquine), venous thromboembolism prophylaxis and advanced respiratory support interventions (prone positioning and extracorporeal membrane oxygenation). Through continuous evidence surveillance, these living recommendations are updated in near real-time to ensure clinicians in Australia have reliable, evidence-based guidelines for clinical decision-making. Please visit https://covid19evidence.net.au/ for the latest recommendation updates.Copyright © 2020 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists

Background: Extracorporeal life support (ECLS) is increasingly used worldwide over the past two decades and new indications are emerging, including extracorporeal cardiopulmonary resuscitation, trauma and COVID-19 cases. A frequent and remained feared complication is bleeding, and it is associated with high morbidity and mortality. However, trends of bleeding complications and outcomes have been poorly investigated. Method(s): Veno-venous (V-V) and veno-arterial (V-A) ECLS patients from the Extracorporeal Life Support Organization (ELSO) Registry database between 2000 and 2020 were included. Bleeding complication and mortality trends were analyzed. Bleeding complications included surgical site, cannulation site, gastrointestinal, pulmonary central nervous system and tamponade bleeding. Risk factors for bleeding complications were identified with multivariable analysis. Result(s): The analysis included 50.444 patients with single ECLS runs, 30.696 patients with V-A ECLS and 19.748 with V-V ECLS. Bleeding complications were reported in 13.534 patients (26.8%) and occurred more often in V-A ECLS compared to V-V ECLS patients (30.0% versus 21.9%). Bleeding patients showed lower hospital survival rates in both groups. Over the past twenty years bleeding complications showed a decreasing trend with a coefficient of -1.124 and -1.661 for V-V and V-A ECLS respectively. Surgical and cannulation site bleeding showed highest negative trend in both ECLS groups. Conclusion(s): The decrease in bleeding complications, especially cannulation and surgical site related bleeding, over the past two decades suggest improvement in anticoagulation management and possible equipment development. However, the persistent high rates of bleeding complications and association with mortality reinforces the need to understand bleeding complications more thoroughly during ECLS.

PURPOSE OF REVIEW: Recent advances in the understanding of the pathophysiological processes associated with traumatic haemorrhage and trauma-induced coagulopathy (TIC) have resulted in improved outcomes for seriously injured trauma patients. However, a significant number of trauma patients still die from haemorrhage. This article reviews the role of fibrinogen in normal haemostasis, the effect of trauma and TIC on fibrinogen levels and current evidence for fibrinogen replacement in the management of traumatic haemorrhage. RECENT FINDINGS: Fibrinogen is usually the first factor to reach critically low levels in traumatic haemorrhage and hypofibrinogenaemia after severe trauma is associated with increased risk of massive transfusion and death. It is postulated that the early replacement of fibrinogen in severely injured trauma patients can improve outcomes. There is, however, a paucity of evidence to support this, and in addition, there is little evidence to support or refute the effects of cryoprecipitate or fibrinogen concentrate for fibrinogen replacement. SUMMARY: The important role fibrinogen plays in haemostasis and effective clot formation is clear. A number of pilot trials have investigated different strategies for fibrinogen replacement in severe trauma. These trials have formed the basis of several large-scale phase III trials, which, cumulatively will provide a firm evidence base to harmonise worldwide clinical management of severely injured trauma patients with major haemorrhage.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Background: Prophylactic immunoglobulin (Ig) replacement and prophylactic oral antibiotics (PA) are used to prevent infections in patients with haematological malignancies and acquired hypogammaglobulinemia. Ig has been shown to reduce infection risk, but is costly and in limited supply. PA have been shown to reduce infection risk in other patient populations and are less expensive, but have side-effects and can increase antimicrobial resistance rates. Guidelines and clinical practice vary internationally, with some recommending a trial of PA prior to commencing Ig replacement, and others omitting PA. The efficacy, safety and cost-effectiveness of Ig and PA have not been directly compared in a randomised controlled trial (RCT) in patients with acquired hypogammaglobulinemia secondary to haematological malignancies. Aim(s): To determine the feasibility of delivering PA as an alternative to Ig replacement in patients with haematological malignancies and acquired hypogammaglobulinemia. Method(s): Phase II, multicentre, feasibility RCT (ACTRN12616001723471). Eligible patients had acquired hypogammaglobulinemia due to a haematological malignancy, a history of recurrent or severe bacterial infections or an IgG level <4g/L (excluding paraprotein), and had a life expectancy more than 12 months. Exclusion criteria included prior allogeneic haematopoietic stem cell transplant and prior Ig replacement in the preceding 3 months. Patients were randomised to receive Ig (0.4g/kg IV every 4 weeks, modified to achieve an IgG trough level >= lower limit of reference range; or 0.1g/kg/week SC, modified to achieve an IgG trough level of >= lower limit of reference rage) or daily oral prophylactic antibiotics (trimethoprim-sulfamethoxazole 160mg/800mg, with 100mg doxycycline as an alternative for hypersensitivity) for 12 months at a 1:2 ratio. Randomisation was stratified by site. Patients allocated to PA were allowed to cross over to Ig if they experienced a CTCAE >= Grade 3 infection.

Introduction: There is an increase in use of extracorporeal life support (ECLS) for cardiac support, with new indications emerging. Bleeding complications are the most frequent complications, associated with high morbidity and mortality. Despite the high frequency, the risk factors for bleeding complications remain poorly investigated. Method(s): To develop a prediction model for bleeding complications, adult patients included in the Extracorporeal Life Support Organization (ELSO) registry undergoing V-A ECLS between 2000 and 2020 were analyzed. The primary outcome was bleeding complications during V-A ECLS. Backward stepwise elimination in multivariable logistic regression analysis was used to develop the prediction model. The performance of the model was tested by ROC curves with AUC for discriminative ability and calibration plots. To detect overfitting of the model, internal validation was performed. Result(s): Single V-A ECLS runs were recorded in 28.767 adult patients, of which 29,0% developed bleeding complications. Sex, BMI, surgical cannulation, respiratory and hemodynamic variables prior to ECLS, the use of additional support devices, pre-ECLS interventions and different type of diagnosis were included in the prediction model. The model showed a fair predictive capability with an AUC of 0.66. Internal validation showed almost no overfitting of the model. An online calculator may simplify the use of the model. Conclusion(s): A multivariable model was developed and internally validated to calculate the risk for bleeding complications for adult patients receiving V-A ECLS. This model showed a favorabel predictive capability compared to the current literature. External validation is needed to confirm clinical use of this model.

Background: Extracorporeal life support (ECLS) is increasingly used worldwide over the past two decades and new indications are emerging, including extracorporeal cardiopulmonary resuscitation, trauma and COVID-19 cases. A frequent and remained feared complication is bleeding, and it is associated with high morbidity and mortality. However, trends of bleeding complications and outcomes have been poorly investigated. Method(s): Veno-venous (V-V) and veno-arterial (V-A) ECLS patients from the Extracorporeal Life Support Organization (ELSO) Registry database between 2000 and 2020 were included. Bleeding complication and mortality trends were analyzed. Bleeding complications included surgical site, cannulation site, gastrointestinal, pulmonary central nervous system and tamponade bleeding. Risk factors for bleeding complications were identified with multivariable analysis. Result(s): The analysis included 50.444 patients with single ECLS runs, 30.696 patients with V-A ECLS and 19.748 with V-V ECLS. Bleeding complications were reported in 13.534 patients (26.8%) and occurred more often in V-A ECLS compared to V-V ECLS patients (30.0% versus 21.9%). Bleeding patients showed lower hospital survival rates in both groups. Over the past twenty years bleeding complications showed a decreasing trend with a coefficient of -1.124 and -1.661 for V-V and V-A ECLS respectively. Surgical and cannulation site bleeding showed highest negative trend in both ECLS groups. Conclusion(s): The decrease in bleeding complications, especially cannulation and surgical site related bleeding, over the past two decades suggest improvement in anticoagulation management and possible equipment development. However, the persistent high rates of bleeding complications and association with mortality reinforces the need to understand bleeding complications more thoroughly during ECLS.

Background: Prophylactic immunoglobulin (Ig) replacement and prophylactic oral antibiotics (PA) are used to prevent infections in patients with haematological malignancies and acquired hypogammaglobulinemia. Ig has been shown to reduce infection risk, but is costly and in limited supply. PA have been shown to reduce infection risk in other patient populations and are less expensive, but have side-effects and can increase antimicrobial resistance rates. Guidelines and clinical practice vary internationally, with some recommending a trial of PA prior to commencing Ig replacement, and others omitting PA. The efficacy, safety and cost-effectiveness of Ig and PA have not been directly compared in a randomised controlled trial (RCT) in patients with acquired hypogammaglobulinemia secondary to haematological malignancies. Aim(s): To determine the feasibility of delivering PA as an alternative to Ig replacement in patients with haematological malignancies and acquired hypogammaglobulinemia. Method(s): Phase II, multicentre, feasibility RCT (ACTRN12616001723471). Eligible patients had acquired hypogammaglobulinemia due to a haematological malignancy, a history of recurrent or severe bacterial infections or an IgG level <4g/L (excluding paraprotein), and had a life expectancy more than 12 months. Exclusion criteria included prior allogeneic haematopoietic stem cell transplant and prior Ig replacement in the preceding 3 months. Patients were randomised to receive Ig (0.4g/kg IV every 4 weeks, modified to achieve an IgG trough level >= lower limit of reference range; or 0.1g/kg/week SC, modified to achieve an IgG trough level of >= lower limit of reference rage) or daily oral prophylactic antibiotics (trimethoprim-sulfamethoxazole 160mg/800mg, with 100mg doxycycline as an alternative for hypersensitivity) for 12 months at a 1:2 ratio. Randomisation was stratified by site. Patients allocated to PA were allowed to cross over to Ig if they experienced a CTCAE >= Grade 3 infection.

Introduction: There is an increase in use of extracorporeal life support (ECLS) for cardiac support, with new indications emerging. Bleeding complications are the most frequent complications, associated with high morbidity and mortality. Despite the high frequency, the risk factors for bleeding complications remain poorly investigated. Method(s): To develop a prediction model for bleeding complications, adult patients included in the Extracorporeal Life Support Organization (ELSO) registry undergoing V-A ECLS between 2000 and 2020 were analyzed. The primary outcome was bleeding complications during V-A ECLS. Backward stepwise elimination in multivariable logistic regression analysis was used to develop the prediction model. The performance of the model was tested by ROC curves with AUC for discriminative ability and calibration plots. To detect overfitting of the model, internal validation was performed. Result(s): Single V-A ECLS runs were recorded in 28.767 adult patients, of which 29,0% developed bleeding complications. Sex, BMI, surgical cannulation, respiratory and hemodynamic variables prior to ECLS, the use of additional support devices, pre-ECLS interventions and different type of diagnosis were included in the prediction model. The model showed a fair predictive capability with an AUC of 0.66. Internal validation showed almost no overfitting of the model. An online calculator may simplify the use of the model. Conclusion(s): A multivariable model was developed and internally validated to calculate the risk for bleeding complications for adult patients receiving V-A ECLS. This model showed a favorabel predictive capability compared to the current literature. External validation is needed to confirm clinical use of this model.

To date, 18 living recommendations for the clinical care of pregnant and postpartum women with COVID-19 have been issued by the National COVID-19 Clinical Evidence Taskforce. This includes recommendations on mode of birth, delayed umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, antenatal corticosteroids, angiotensin-converting enzyme inhibitors, disease-modifying treatments (including dexamethasone, remdesivir and hydroxychloroquine), venous thromboembolism prophylaxis and advanced respiratory support interventions (prone positioning and extracorporeal membrane oxygenation). Through continuous evidence surveillance, these living recommendations are updated in near real-time to ensure clinicians in Australia have reliable, evidence-based guidelines for clinical decision-making. Please visit https://covid19evidence.net.au/ for the latest recommendation updates.Copyright © 2020 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists

PURPOSE OF REVIEW: Recent advances in the understanding of the pathophysiological processes associated with traumatic haemorrhage and trauma-induced coagulopathy (TIC) have resulted in improved outcomes for seriously injured trauma patients. However, a significant number of trauma patients still die from haemorrhage. This article reviews the role of fibrinogen in normal haemostasis, the effect of trauma and TIC on fibrinogen levels and current evidence for fibrinogen replacement in the management of traumatic haemorrhage. RECENT FINDINGS: Fibrinogen is usually the first factor to reach critically low levels in traumatic haemorrhage and hypofibrinogenaemia after severe trauma is associated with increased risk of massive transfusion and death. It is postulated that the early replacement of fibrinogen in severely injured trauma patients can improve outcomes. There is, however, a paucity of evidence to support this, and in addition, there is little evidence to support or refute the effects of cryoprecipitate or fibrinogen concentrate for fibrinogen replacement. SUMMARY: The important role fibrinogen plays in haemostasis and effective clot formation is clear. A number of pilot trials have investigated different strategies for fibrinogen replacement in severe trauma. These trials have formed the basis of several large-scale phase III trials, which, cumulatively will provide a firm evidence base to harmonise worldwide clinical management of severely injured trauma patients with major haemorrhage.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

We present a case of late symptom onset of COVID-19 infection 72 days after initial diagnosis in an immunocompromised 53-year-old man. SARS-CoV-2 was cultured from his sputum sample at this time, and genomic sequencing suggested reinfection was unlikely. After receipt of convalescent plasma, SARS-CoV-2 became undetectable by PCR 111 days after diagnosis, although SARS-CoV-2 antibodies remained not detectable. This case posed difficult public health management issues in a low prevalence COVID-19 setting as the person required extended home isolation given his prolonged SARS-CoV-2 PCR detection.Copyright © 2021 by The Society for Healthcare Epidemiology of America. All rights reserved.

BACKGROUND: As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection to SARS-CoV-2, ideally with rapid turnaround and without the need for laboratory-based testing. METHODS: We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibody (NAb) from whole blood, with a result that can be determined by eye or quantitatively on a small instrument. We compared our lateral flow test with the gold-standard microneutralisation assay, using samples from convalescent and vaccinated donors, as well as immunised macaques. FINDINGS: We show a high correlation between our lateral flow test with conventional neutralisation and that this test is applicable with animal samples. We also show that this assay is readily adaptable to test for protection to newly emerging SARS-CoV-2 variants, including the beta variant which revealed a marked reduction in NAb activity. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (specificity 100% and sensitivity 96% at a microneutralisation cutoff of 1:40) and that fingerprick whole blood samples are sufficient for this test. INTERPRETATION: Taken together, the COVID-19 NAb-testTM device described here provides a rapid readout of NAb based protection to SARS-CoV-2 at the point of care. FUNDING: Support was received from the Victorian Operational Infrastructure Support Program and the Australian Government Department of Health. This work was supported by grants from the Department of Health and Human Services of the Victorian State Government; the ARC (CE140100011, CE140100036), the NHMRC (1113293, 2002317 and 1116530), and Medical Research Future Fund Awards (2005544, 2002073, 2002132). Individua

Contains fulltext : 238101.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagul

Contains fulltext : 238100.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulati

Contains fulltext : 238101.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagul

Contains fulltext : 238100.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulati

Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of

Aim: To determine the feasibility of an electronic dataset comprising hospital laboratory data, transfusion data (any fresh or manufactured product) and clinical outcomes in Australian hospitals. To provide a 'issing link' in monitoring alignment of practice with, and impact of, Australian national patient blood management (PBM) policies and guidelines. Method(s): Using the platform of the Australian and New Zealand Massive Transfusion Registry, all data from adult patients transfused any blood product at participating sites for 2017, including laboratory (for transfusion and other laboratory records) and hospital information systems data (for patient demographics, co-morbidities, admission and clinical outcome data) were extracted. Data were securely sent, imported into the database and data linkage algorithms applied. Analyses were performed using Stata software. Result(s): Selected results from data analyses of the first pilot site are presented. During 2017, 5859 patients received at least 1 transfusion product during a total of 11 201 separate admissions; of these, 3407 (30%) were day-admissions. Length-of-stay (LoS) was >=10 days for 51% of admissions. 21% of hospital stays included ICU admission, of which 25% (577/2307 ICU admissions) were >10 days LoS in ICU. In-hospital mortality was 9.6% (565 deaths/5859 patients), of which 28 deaths (5% of 565 deaths) were LoS <1-day Emergency admissions. Transfused blood products included 24 766 RBC (red blood cells), 9365 PLT (platelets), 7701 FFP (fresh frozen plasma), 4422 Cryo (cryoprecipitate), 52 251 grams IVIg (intravenous immunoglobulin) and 6301 vials of Prothrombinex. Conclusion(s): This study demonstrates feasibility of a potential national dataset linking comprehensive information from readily available electronic hospital data sources on all patients transfused any type of blood product, including immunoglobulins and coagulation factor concentrates, with clinical outcomes data adjusted for demographics and c

Aim: Using Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR) describe Whole Blood (WB) use in massive transfusion (MT) (>=5 red blood cells (RBC) in any 4 h period) in NZ and compare transfusion requirements, laboratory parameters and patient outcomes for WB recipients (WB-R) with those receiving only RBC units (RBC-R). Method(s): All adult MT recipients between 2011 and 2018, at 4 NZ sites with access to WB, were included in the analysis. Result(s): Three hundred fifteen of 1947 (16.1%) MT recipients received >=1 WB unit. WB was most commonly used in vascular surgery (21%), trauma (17%), gastrointestinal (14%), cardiac surgery (11%). WB-R received a median of 2 (IQR 1, 2) WB units and commenced transfusion sooner relative to time of hospital admission than RBC-R. WB-R received fewer RBC (9 (6,16) vs 10 (7,15), P = 0.013), more fresh frozen plasma (FFP) (6 (2,11) vs 5 (2, 9), p < 0.001) and more recombinant FVIIa (P = 0.02) than RBC-R. There were no differences in fibrinogen concentrate, prothrombin complex or other fresh blood products given. In first 4-h of MT, WB-R had shorter APTT compared to RBC-R (42 (34, 60) vs 47 (36, 71) seconds; P = 0.01). Nadir haemoglobin, platelet count and fibrinogen for the 2 groups were similar. WB-R had higher in-hospital mortality (31.4% vs 25.3%, P = 0.024), but similar ICU length of stay and ventilation time. After adjusting for age, sex, number of RBC and FFP units, clinical context and hospital site there was no significant association between WB use and mortality (adjusted odds ratio WB Plasma Reduced 1.19 (95% CI 0.80-1.78) and WB Leucodepleted 1.42 (95% CI 0.94-2.15)).

Aim: Patients with haematologic malignancies are major recipients of blood products; however comprehensive Australian data about clinical outcomes of transfusion are limited. As part of a feasibility study to establish a national comprehensive dataset of all transfusions and their outcomes, we analysed transfusion data for adult haematology/oncology patients from the first pilot site. Method(s): Hospital electronic data on adult patients receiving any blood product (>=1 RBC [red blood cells], platelet, FFP [fresh frozen plasma], cryoprecipitate, or plasma derivative) during 2017 were imported, linked and analysed using the expanded platform of the Australian and New Zealand Massive Transfusion Registry. Data included laboratory (for transfusion and blood tests) and hospital information systems records (for patient demographics, co-morbidities, admission and clinical outcome data). Haematology/oncology patients were identified by ICD-10-AM diagnostic codes. Analyses were performed using Stata software. Result(s): Of 5859 transfused admitted patients, 767 (13%) were haematology/ oncology patients. Of these 38% were acute leukaemias, 25% myeloma, 15% NHL (non-Hodgkin lymphoma), 7% chronic leukaemias, and 15% MDS and other haematopoietic neoplasms. Patient median age was 66.7y, [IQR, 57, 74], and 58% were male. Haematology/oncology patients were 30% (3365/11201) of all admissions where a transfusion was performed; of which 56% were day-admissions. 61% of patients were admitted only once; 34% had 2-10 admissions and 5% had 11-100 admissions. They accounted for 33% RBCs, 69% platelets, 20% cryoprecipitate, 5% FFP and 13% IVIg (intravenous immunoglobulin; in grams) transfused. For outpatients receiving platelet transfusions, median [IQR] platelet count was 17 x109/L [10, 51]. Conclusion(s): Haematology/oncology patients represented 13% of all transfused patients, but required significant proportions of the transfusion product inventory, including 69% of all platelets, cons

The role of cytarabine-based induction and autologous stem cell transplantation (ASCT) in front-line treatment of younger patients with mantle cell lymphoma (MCL) is well established, however the utility of intensive approaches in older patients remains unclear. This retrospective study compared first line treatment outcomes in patients aged 60 years or more, treated at six tertiary centres between 2000-2015. 70 patients included had a median age of 69 (60-91) and most (94%) demonstrated advanced stage disease. Treatment regimens included: R-CHOP-like (n=39), alternating R-CHOP/R-DHAC (n=10), R-HyperCVAD/R-MA (n=7), R-CHOP/Cytarabine (Nordic Protocol) (n=10) and other (n=4). 16 patients underwent an ASCT. The median follow-up for surviving patients was 37 months. Compared to R-CHOP-like therapies, cytarabine-based regimens were associated with an improved overall response rate (ORR) of 70% vs 33% (p<0.001) and overall survival (OS) (HR 0.541, [0.292-1.001], p=0.05). No difference in efficacy between different cytarabine-based regimens was detected, but R-HyperCVAD/R-MA was associated with increased hospitalisation and transfusion requirements. Patients undergoing ASCT demonstrated an improved median OS (HR 0.108 [0.015-0.796], p=0.029) but were significantly younger. These results reaffirm the use of cytarabine in MCL for selected patients aged over 60. Such regimens should be strongly considered for this population in frontline therapy.

Aim: To determine the feasibility of an electronic dataset comprising hospital laboratory data, transfusion data (any fresh or manufactured product) and clinical outcomes in Australian hospitals. To provide a 'issing link' in monitoring alignment of practice with, and impact of, Australian national patient blood management (PBM) policies and guidelines. Method(s): Using the platform of the Australian and New Zealand Massive Transfusion Registry, all data from adult patients transfused any blood product at participating sites for 2017, including laboratory (for transfusion and other laboratory records) and hospital information systems data (for patient demographics, co-morbidities, admission and clinical outcome data) were extracted. Data were securely sent, imported into the database and data linkage algorithms applied. Analyses were performed using Stata software. Result(s): Selected results from data analyses of the first pilot site are presented. During 2017, 5859 patients received at least 1 transfusion product during a total of 11 201 separate admissions; of these, 3407 (30%) were day-admissions. Length-of-stay (LoS) was >=10 days for 51% of admissions. 21% of hospital stays included ICU admission, of which 25% (577/2307 ICU admissions) were >10 days LoS in ICU. In-hospital mortality was 9.6% (565 deaths/5859 patients), of which 28 deaths (5% of 565 deaths) were LoS <1-day Emergency admissions. Transfused blood products included 24 766 RBC (red blood cells), 9365 PLT (platelets), 7701 FFP (fresh frozen plasma), 4422 Cryo (cryoprecipitate), 52 251 grams IVIg (intravenous immunoglobulin) and 6301 vials of Prothrombinex. Conclusion(s): This study demonstrates feasibility of a potential national dataset linking comprehensive information from readily available electronic hospital data sources on all patients transfused any type of blood product, including immunoglobulins and coagulation factor concentrates, with clinical outcomes data adjusted for demographics and c

The role of cytarabine-based induction and autologous stem cell transplantation (ASCT) in front-line treatment of younger patients with mantle cell lymphoma (MCL) is well established, however the utility of intensive approaches in older patients remains unclear. This retrospective study compared first line treatment outcomes in patients aged 60 years or more, treated at six tertiary centres between 2000-2015. 70 patients included had a median age of 69 (60-91) and most (94%) demonstrated advanced stage disease. Treatment regimens included: R-CHOP-like (n=39), alternating R-CHOP/R-DHAC (n=10), R-HyperCVAD/R-MA (n=7), R-CHOP/Cytarabine (Nordic Protocol) (n=10) and other (n=4). 16 patients underwent an ASCT. The median follow-up for surviving patients was 37 months. Compared to R-CHOP-like therapies, cytarabine-based regimens were associated with an improved overall response rate (ORR) of 70% vs 33% (p<0.001) and overall survival (OS) (HR 0.541, [0.292-1.001], p=0.05). No difference in efficacy between different cytarabine-based regimens was detected, but R-HyperCVAD/R-MA was associated with increased hospitalisation and transfusion requirements. Patients undergoing ASCT demonstrated an improved median OS (HR 0.108 [0.015-0.796], p=0.029) but were significantly younger. These results reaffirm the use of cytarabine in MCL for selected patients aged over 60. Such regimens should be strongly considered for this population in frontline therapy.

Aim: Using Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR) describe Whole Blood (WB) use in massive transfusion (MT) (>=5 red blood cells (RBC) in any 4 h period) in NZ and compare transfusion requirements, laboratory parameters and patient outcomes for WB recipients (WB-R) with those receiving only RBC units (RBC-R). Method(s): All adult MT recipients between 2011 and 2018, at 4 NZ sites with access to WB, were included in the analysis. Result(s): Three hundred fifteen of 1947 (16.1%) MT recipients received >=1 WB unit. WB was most commonly used in vascular surgery (21%), trauma (17%), gastrointestinal (14%), cardiac surgery (11%). WB-R received a median of 2 (IQR 1, 2) WB units and commenced transfusion sooner relative to time of hospital admission than RBC-R. WB-R received fewer RBC (9 (6,16) vs 10 (7,15), P = 0.013), more fresh frozen plasma (FFP) (6 (2,11) vs 5 (2, 9), p < 0.001) and more recombinant FVIIa (P = 0.02) than RBC-R. There were no differences in fibrinogen concentrate, prothrombin complex or other fresh blood products given. In first 4-h of MT, WB-R had shorter APTT compared to RBC-R (42 (34, 60) vs 47 (36, 71) seconds; P = 0.01). Nadir haemoglobin, platelet count and fibrinogen for the 2 groups were similar. WB-R had higher in-hospital mortality (31.4% vs 25.3%, P = 0.024), but similar ICU length of stay and ventilation time. After adjusting for age, sex, number of RBC and FFP units, clinical context and hospital site there was no significant association between WB use and mortality (adjusted odds ratio WB Plasma Reduced 1.19 (95% CI 0.80-1.78) and WB Leucodepleted 1.42 (95% CI 0.94-2.15)).

Aim: Patients with haematologic malignancies are major recipients of blood products; however comprehensive Australian data about clinical outcomes of transfusion are limited. As part of a feasibility study to establish a national comprehensive dataset of all transfusions and their outcomes, we analysed transfusion data for adult haematology/oncology patients from the first pilot site. Method(s): Hospital electronic data on adult patients receiving any blood product (>=1 RBC [red blood cells], platelet, FFP [fresh frozen plasma], cryoprecipitate, or plasma derivative) during 2017 were imported, linked and analysed using the expanded platform of the Australian and New Zealand Massive Transfusion Registry. Data included laboratory (for transfusion and blood tests) and hospital information systems records (for patient demographics, co-morbidities, admission and clinical outcome data). Haematology/oncology patients were identified by ICD-10-AM diagnostic codes. Analyses were performed using Stata software. Result(s): Of 5859 transfused admitted patients, 767 (13%) were haematology/ oncology patients. Of these 38% were acute leukaemias, 25% myeloma, 15% NHL (non-Hodgkin lymphoma), 7% chronic leukaemias, and 15% MDS and other haematopoietic neoplasms. Patient median age was 66.7y, [IQR, 57, 74], and 58% were male. Haematology/oncology patients were 30% (3365/11201) of all admissions where a transfusion was performed; of which 56% were day-admissions. 61% of patients were admitted only once; 34% had 2-10 admissions and 5% had 11-100 admissions. They accounted for 33% RBCs, 69% platelets, 20% cryoprecipitate, 5% FFP and 13% IVIg (intravenous immunoglobulin; in grams) transfused. For outpatients receiving platelet transfusions, median [IQR] platelet count was 17 x109/L [10, 51]. Conclusion(s): Haematology/oncology patients represented 13% of all transfused patients, but required significant proportions of the transfusion product inventory, including 69% of all platelets, cons

Anaemia is a major public health issue, affecting 25% of the population worldwide according to the World Health Organization. Iron deficiency is responsible for approximately half of all cases globally, with other causes including anaemia of chronic disease, other nutritional deficiencies, haemoglobinopathies, renal impairment, malignancy and bone marrow disease. In the elderly, where anaemia is even more common, the cause is frequently multifactorial. Anaemia is associated with increased mortality, decreased cognitive and physical function, depressive symptoms and fatigue, particularly in older adults. Poor outcomes have also been reported in anaemic patients with underlying comorbidities such as cardiac and renal disease, and cancer. Within a hospital setting, anaemia is highly prevalent. Preoperative anaemia, affecting up to 30% of patients, is associated with poor clinical outcomes including higher in-hospital mortality, longer length of stay and higher ICU admission rates. Anaemia management requires a proactive and multi-faceted approach, typically involving a multi-disciplinary team in which the transfusion practitioner plays a vital role. This includes screening of high-risk patients and pre-admission clinics to identify and manage patients at high risk of peri-operative anaemia. Implementation of patient blood management (PBM) guideline recommendations has been shown to be effective to prevent and optimally manage anaemia within the community and hospital settings. The transfusion practitioner has key roles in the coordination, monitoring and auditing of PBM programs. Active patient involvement and engagement of all members of the multidisciplinary team, including primary care clinicians, are also key to enhance the success of such programs.

Background: Patients with haematological malignancies often develop thrombocytopenia as a consequence of either their disease or its treatment. Platelet transfusions are commonly given to raise a low platelet count and reduce the risk of clinical bleeding (prophylaxis) or stop active bleeding (therapy). Recent studies have shown that many patients continue to experience bleeding despite the use of prophylactic platelet transfusions. Tranexamic acid is an anti-fibrinolytic, which reduces the breakdown of clots formed in response to bleeding. Anti-fibrinolytics have been shown to prevent bleeding, decrease blood loss and use of red cell transfusions in elective and emergency surgery, and are used widely in these settings. The aim of this trial is to test whether giving tranexamic acid to patients receiving treatment for haematological malignancies reduces the risk of bleeding or death and the need for platelet transfusions. Method(s): This is a multinational randomised, double-blind, placebo-controlled, parallel, superiority trial. Patients will be randomly assigned to receive tranexamic acid (given intravenously or orally) or a matching placebo in a 1:1 ratio, stratified by site. Patients with haematological malignancies receiving intensive chemotherapy or stem cell transplantation (or both) who are at least 18 years of age and expected to become severely thrombocytopenic for at least 5 days will be eligible for this trial. The primary outcome of the trial is the proportion of patients who died or had bleeding of World Health Organization grade 2 or above during the first 30 days of the trial. We will measure the rates of bleeding daily by using a short, structured assessment of bleeding, and we will record the number of transfusions given to patients. We will assess the risk of arterial and venous thrombosis for 120 days from the start of trial treatment. Discussion(s): This trial will assess the safety and efficacy of using prophylactic tranexamic acid during a per