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.

No abstract

Background After admission to intensive care, women have higher mortality rates than do men. The reasons for the greater mortality in women are not fully understood. Objective To determine if increased mortality in women was due to delays in the recognition of critical illness or to delays in timely admission to intensive care. Methods A total of 241 consecutive admissions to intensive care from medical and surgical units during a 12-month period were analyzed retrospectively. Patients' demographics, illness severity, and delay between the time the patients would have fulfilled criteria for calling a medical emergency team and consultation with and admission to intensive care were analyzed. Results Delay from fulfillment of criteria for calling a medical emergency team and consultation with intensive care and from consultation to admission to intensive care did not differ between sexes. Despite similar delays in admission to intensive care, women had a higher 30-day mortality than did men (44.9% vs 30.5%; P = .02). The increased mortality was more pronounced in the medical patients (53% vs 34%; P = .02). Multivariate analysis of mortality data yielded a mortality odds ratio of 0.35 (95% CI, 0.16-0.74) for men, significantly different from values for women (P = .006). Conclusion After admission to intensive care from medical or surgical units, women had higher mortality rates than did men, and the difference was more pronounced in medical patients.

Implementation of an ICU consult service without any formal afferent limb training was associated with decreased mortality and 14-day readmission rates of patients admitted to the ICU. In contrast, hospital-wide mortality and code blue rates were unaffected.

Background. Medical emergency teams (METs) or rapid response teams (RRTs) facilitate early intervention for clinically deteriorating hospitalized patients. In healthcare systems where financial resources and intensivist availability are limited, the establishment of such teams can prove challenging. Objectives. A low-cost, ward-based response system was implemented on a medical clinical teaching unit in a Montreal tertiary care hospital. A prospective before/after study was undertaken to examine the system's impact on time to intervention, code blue rates, and ICU transfer rates. Results. Ninety-five calls were placed for 82 patients. Median time from patient decompensation to intervention was 5 min (IQR 1–10), compared to 3.4 hours (IQR 0.6–12.4) before system implementation (p < 0.001). Total number of ICU admissions from the CTU was reduced from 4.8/1000 patient days (±2.2) before intervention to 3.3/1000 patient days (±1.4) after intervention (IRR: 0.82, p = 0.04 (CI 95%: 0.69–0.99)). CTU code blue rates decreased from 2.2/1000 patient days (±1.6) before intervention to 1.2/1000 patient days (±1.3) after intervention (IRR: 0.51, p = 0.02 (CI 95%: 0.30–0.89)). Conclusion. Our local ward-based response system achieved a significant reduction in the time of patient decompensation to initial intervention, in CTU code blue rates, and in CTU to ICU transfers without necessitating additional usage of financial or human resources.

Late-stage erythroid cells synthesize large quantities of haemoglobin, a process requiring the co-ordinated regulation of globin and haem synthesis as well as iron uptake. In the present study, we investigated the role of the ERK (extracellular-signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) signalling pathways in MEL (mouse erythroleukaemia) cell differentiation. We found that treatment of HMBA (hexamethylene bisacetamide)-induced MEL cells with the ERK pathway inhibitor UO126 results in an increase in intracellular haem and haemoglobin levels. The transcript levels of the genes coding for β(major)-globin, the haem biosynthesis enzyme 5-aminolevulinate synthase 2 and the mitochondrial iron transporter mitoferrin 1 are up-regulated. We also showed enhanced expression of globin and transferrin receptor 1 proteins upon UO126 treatment. With respect to iron uptake, we found that ERK inhibitor treatment led to an increase in both haem-bound and total iron. In contrast, treatment of MEL cells with the p38 MAPK pathway inhibitor SB202190 had the opposite effect, resulting in decreased globin expression, haem synthesis and iron uptake. Reporter assays showed that globin promoter and HS2 enhancer-mediated transcription was under the control of MAPKs, as inhibition of the ERK and p38 MAPK pathways led to increased and decreased gene activity respectively. Our present results suggest that the ERK1/2 and p38α/β MAPKs play antagonistic roles in HMBA-induced globin gene expression and erythroid differentiation. These results provide a novel link between MAPK signalling and the regulation of haem biosynthesis and iron uptake in erythroid cells.

IntroductionThere is high variability amongst physicians’ assessments of appropriate ICU admissions, which may be based on potential assessments of benefit. We aimed to examine whether opinions over benefit of ICU admissions of critically ill medical inpatients differed based on physician specialty, namely intensivists and internists.Materials and MethodsWe carried out an anonymous, web-based questionnaire survey containing 5 typical ICU cases to all ICU physicians regardless of their base specialty as well as to all internists in 3 large teaching hospitals. For each case, we asked the participants to determine if the patient was an appropriate ICU admission and to assess different parameters (e.g. baseline function, likelihood of survival to ICU discharge, etc.). Agreement was measured using kappa values.Results21 intensivists and 22 internists filled out the survey (response rate = 87.5% and 35% respectively). Predictions of likelihood of survival to ICU admission, hospital discharge and return to baseline were not significantly different between the two groups. However, agreement between individuals within each group was only slight to fair (kappa range = 0.09–0.22). There was no statistically significant difference in predicting ICU survival and prediction of survival to hospital discharge between both groups. The accuracy with which physicians predicted actual outcomes ranged between 35% and 100% and did not significantly differ between the two groups. A greater proportion of internists favoured non resuscitative measures (24.6% of intensivists and 46.9% internists [p = 0.002]).ConclusionIn a case-based survey, physician specialty base did not affect assessments of ICU admission benefit or accuracy in outcome prediction, but resulted in a statistically significant difference in level of care assignments. Of note, significant disagreement amongst individuals in each group was found.

No abstract