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Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

This study is a further analysis of the TOPPS trial data and assesses patients' baseline characteristics at enrolment, burden of thrombocytopenia, presence of fever and presence of minor hemorrhage as potential risk factors for WHO grade 2 to 4 bleeding. Recurrent event analyses have been used to allow assessment of bleeding over the 30-day trial period and to account for multiple bleeds per patient. MethodsDetails of the UK and Australian TOPPS randomized trial have been published previously .2,8,10 Six hundred patients were randomized to receive either prophylactic platelet transfusions if the platelet count was <10x10 9 /L (n=299), or no prophylaxis (n=301). The trial was approved by independent ethics committees. Although the median number of days with complete data was 30, bleeding data were not complete for all 30 days for all patients. The vast majority of bleeds were inpatient bleeds 8 and, as incomplete records often related to when the patient was at home, no bleeding was assumed on days for which no data were reported.Bleeding types were grouped to describe characteristics of bleeding: skin bruising included petechiae, purpura, and bruising; gastrointestinal bleeding included blood in the stool, melena and hematemesis; mouth bleeding included oral blood blisters and oropharyngeal bleeding; and other included musculoskeletal or deep tissue bleeding, eyes and visual impairment, pleural tap, and cerebral bleeds.For the modeling (Figure 1), patients were grouped by treatment plan [autologous hematopoietic stem cell transplant (HSCT) and chemotherapy (induction and consolidation)/allogeneic HSCT (myeloablative and reduced intensity)] and diagnosis [acute myeloid leukemia (AML), myeloma, lymphoma and other diagnoses]. In contrast to the TOPPS analysis, only the first day of consecutive bruising or petechiae was counted as a bleed, unless bleeding on the subsequent day was worse. Modeling analysisNegative binomial regression 11 was used to model baseline characteristics associated with the number of days of grade 2-4 bleeding (analysis 1). The risk factors considered are shown in Table 1. Previous HSCT (defined as any prior transplant) and relapsed disease were also considered.Recurrent event analysis 12 was used to model the hazard of a grade 2-4 bleed on any one day, accounting for previous bleeds (analyses 2a, 2b and 2c). Robust sandwich variance estimates 12 were used for the hazard confidence intervals. Analysis 2a was the main recurrent event analysis. Analysis 2b was performed on a subset of bleeding records in which the platelet count from all 3 previous days was reported. Analysis 2c was a further subset analysis in which patients' temperature from all 3 previous days Risk factors for bleeding and platelet transfusion haematologica | 2015; 100(6) 741 Figure 1. Shows the number of patients (Np) and number of bleeding records (Nr) included in each part of the analysis.Eight of the 600 patients in the TOPPS trial dataset were not included in the analyses described in this paper: two patients w...

A comprehensive search yielded 121 confirmed cases of Creutzfeldt-Jakob disease who died in England and Wales in the decade 1970-1979, 31 probable cases and 10 possible cases. Descriptive epidemiological data are presented. The average annual incidence was 0 3 cases/million. An unexpected female excess was found. There was no evidence of space-time clustering of cases and no associations with occupation or past medical treatment were apparent. There was statistically significant variation in incidence rates in different parts of the country but no relationship was discovered between incidence and population density. Creutzfeldt-Jakob disease was first transmitted to the chimpanzee in 1968,' but despite extensive subsequent investigation no means of natural transmission has been discovered. Lateral transmission of an agent is thought to occur in scrapie,2 transmissible mink encephalopathy,3 and kuru4 but, with the exception of rare cases of iatrogenic transmission and possible contact transmission with familial cases, has not been described in Creutzfeldt-Jakob disease. As part of an epidemiological survey of the disease in England and Wales a retrospective survey was undertaken for the decade 1970-1979. The present communication is concerned with the epidemiological aspects of the survey. Methods Cases were ascertained from three sources. The primary source of cases was from death certificates. The 8th ICD revision, which was in use between 1970-1978, did not have a separate code for Creutzfeldt-Jakob disease and it was first necessary to define rubrics likely to include patients dying of Creutzfeldt-Jakob disease. Death certificates for the year 1973 was available on microfilm at the Office of Population Censuses and Surveys, and all certificates coded under rubrics 348, 290-0, 290-1, 333.9, 347.9, 3319 and 342 were examined for mention of Creutzfeldt-Jakob disease or Subacute Spongiform Encephalopathy. (A list of rubrics is appended.) Two cases certified as Creutzfeldt-Jakob disease were coded under rubric 290-1 and twelve cases under rubric Address for reprint requests: RG Will,

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