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.

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Background The synchronised monthly disbursement of income assistance, whereby all recipients are paid on the same day, has been associated with increases in illicit drug use and serious associated harms. This phenomenon is often referred to as the cheque effect. Because payment variability can affect consumption patterns, this study aimed to assess whether these harms could be mitigated through a structural intervention that varied income assistance payment timing and frequency.Methods This randomised, parallel group trial was done in Vancouver, Canada, and enrolled recipients of income assistance whose drug use increased around payment days. The recipients were randomly assigned 1:2:2 to a control group that received monthly synchronised income assistance payments on government payment days, a staggered group in which participants received single desynchronised monthly income assistance payments, or a split and staggered group in which participants received desynchronised income assistance payments split into two instalments per month, 2 weeks apart, for six monthly payment cycles. Desynchronised payments in the intervention groups were made on individual payment days outside the week of the standard government schedules. Randomisation was through a pre-established stratified block procedure. Investigators and statisticians were masked to group allocation, but participants and front-line staff were not. Complete final results are reported after scheduled interim analyses and the resulting early stoppage of recruitment. Under intention-to-treat specifications, generalised linear mixed models were used to analyse the primary outcome, which was escalations in drug use, predefined as a 40% increase in at least one of: use frequency; use quantity; or number of substances used during the 3 days after government payments. Secondary analyses examined analogous drug use outcomes coinciding with individual payments as well as exposure to violence. This trial is registered with ClinicalTrials.gov, NCT02457949.

Background People who use drugs (PWUD) are known to fear calling emergency medical services (EMS) for drug overdoses. In response, drug-related Good Samaritan Laws (GSLs) have been widely adopted in the USA and Canada to encourage bystanders to call emergency medical services (EMS) in the event of a drug overdose. However, the effect of GSLs on EMS-calling behaviours has been understudied. We sought to identify factors associated with EMS-calling, including the enactment of the Canadian GSL in May 2017, among PWUD in Vancouver, Canada, a setting with an ongoing overdose crisis. Methods Data were derived from three prospective cohort studies of PWUD in Vancouver in 2014–2018. Multivariable logistic regression was used to determine factors associated with EMS-calling among PWUD who witnessed an overdose event. An interrupted time series (ITS) analysis was employed to assess the impact of GSL on monthly prevalence of EMS-calling. Results Among 540 eligible participants, 321 (59%) were males and 284 (53%) reported calling EMS. In multivariable analysis, ever having administered naloxone three or more times (adjusted odds ratio [AOR] 2.00; 95% confidence interval [CI] 1.08–3.74) and residence in the Downtown Eastside (DTES) neighbourhood of Vancouver (AOR 1.96; 95% CI 1.23–3.13) were positively associated with EMS-calling, while living in a single occupancy hotel (SRO) was negatively associated with EMS-calling (AOR 0.51; 95% CI 0.30–0.86). The post-GSL enactment period was not associated with EMS-calling (AOR 0.81; 95% CI 0.52–1.25). The ITS found no significant difference in the monthly prevalence of EMS-calling between pre- and post-GSL enactment periods. Conclusion We observed EMS being called about half the time and the GSL did not appear to encourage EMS-calling. We also found that individuals living in SROs were less likely to call EMS, which raises concern given that fatal overdose cases are concentrated in SROs in our setting. The link between many naloxone administrations and EMS-calling could indicate that those with prior experience in responding to overdose events were more willing to call EMS. Increased efforts are warranted to ensure effective emergency responses for drug overdoses among PWUD.