Efficacy and effectiveness of SARS-CoV-2 vaccines for death prevention: A protocol for a systematic review and meta-analysis.

BACKGROUND: There is consistent evidence that SARS-CoV-2 vaccines have statistical and clinical significant efficacy to prevent incident and severe cases of COVID-19, although different outcomes were analyzed and different risk reductions were observed. However, randomized control trials (RCT) were not designed or powered to assess whether the vaccines prevent deaths, even though this was a secondary or exploratory outcome across many studies. Early real-world observational data suggest that these vaccines are highly effective in reducing hospitalization and all-cause mortality. Our objective is to summarize and appraise-the existing evidence on the efficacy and real-world effectiveness of all SARS-CoV-2 vaccines currently approved for full or limited use to prevent all-cause and COVID-19-attributed mortality. METHODS: The population consists of persons with a record of vaccination status and the outcome of interest. Randomized controlled trials, comparative cohort and case-control studies reporting vaccination with any of the vaccines approved (intervention) will be eligible. The primary outcome will be all cause deaths. COVID-19-attributed deaths and deaths attributable to the vaccination (adverse event deaths) will be secondary outcomes. We will compare deaths occurring in vaccinated persons versus those non-vaccinated or having received placebo. Studies in any language will be eligible. Two independent reviewers will screen for inclusion and assess quality of studies using the Cochrane Risk of Bias 2 and the ROBINS-1 tool, as appropriate. Hazard ratios will be calculated. Assessment of statistical heterogeneity amongst the studies will be done using I2 and prediction intervals, as well as visual inspection of the forest plots. Publication bias will be assessed using a funnel plot and Egger statistical test if we have more than 10 studies in a forest plot. We have followed the PRISMA-Protocol checklist for the current protocol, which is registered at Prospero (York University, CRD42021262211).

Factors influencing enoxaparin anti-Xa activity in surgical critically ill patients.

STUDY OBJECTIVE: The objectives of the present study were to describe the incidence of low anti-Xa levels defined as below 0.1 IU/mL in a general surgical intensive care unit population and to evaluate factors independently influencing anti-Xa activity. DESIGN: A prospective study was undertaken. SETTING: Thirty-six patients admitted to a general intensive care unit and receiving subcutaneous (SC) enoxaparin 30 mg twice daily for thromboprophylaxis between November 2003 and August 2005 were included in the study. MEASUREMENTS AND MAIN RESULTS: After reaching steady state, anti-Xa activity was determined by chromogenic assay at 0, 3, 6, and 9 hours after injection. Anti-Xa levels below 0.1 IU/mL at any time were considered subtherapeutic. Areas under the curve (AUCs) for a 12-hour dosing interval were estimated. Factors influencing anti-Xa AUC were evaluated using linear regression. Two patients (5.6%) did not attain therapeutic levels defined as anti-Xa more than 0.1 IU/mL at 3 hours post dose. Median AUC was 1.84 IU·h/mL (interquartile range, 1.47 IU·h/mL). In the linear regression analysis, sex and creatinine clearance were significant predictors of anti-Xa AUC(0-12h) levels. CONCLUSION: In the study, prophylactic SC enoxaparin in critically ill patients at the current 30 mg SC twice daily dosage attained an anti-Xa level more than 0.1 U/mL in nearly all patients. In addition, low creatinine clearances and female sex are associated with higher anti-Xa activity AUC(0-12h).