CERTAIN Program: Logic Model for System Level Planning and Evaluation of Innovative Education Delivery and Dissemination (preprint)

Background: CERTAIN (Checklist for Early Recognition and Treatment of Acute Illness and iNjury) has been shown to improve critical care process and patient outcomes in international ICUs with variable resources. Methods CERTAIN education program derived from this approach is designed, promoted, and implemented following the Logic model. Through the roadmap of the Logic model, we presented a dynamic, longitudinal implementation framework that had sufficient rigor yet offers flexibility to reach the need of the existing and emerging diversified medical education projects. Results Using the Logic model, the delivery of the CERTAIN education program is optimized to deliver relevant education content in various environments. During the COVID-19 outbreak, the implementational framework demonstrated that it could serve as an excellent template for effective response to global pandemics. Conclusions The Logical model is useful as a facilitation tool for planning and evaluating innovative education delivery and dissemination. The CERTAIN program provided an example for other continuous professional education projects.

Association of Obesity with COVID-19 Severity and Mortality: A Systemic Review and Meta-Regression (preprint)

Objective: To estimate the association of obesity with severity (defined as use of invasive mechanical ventilation or intensive care unit admission) and all-cause mortality in coronavirus disease 2019 (COVID-19) patients. Patients and Methods: A systematic search was conducted from inception of COVID-19 pandemic through January 31st, 2021 for full-length articles focusing on the association of increased BMI/ Obesity and outcome in COVID-19 patients with help of various databases including Medline (PubMed), Embase, Science Web, and Cochrane Central Controlled Trials Registry. Preprint servers such as BioRxiv, MedRxiv, ChemRxiv, and SSRN were also scanned. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used for study selection and data extraction. The severity in hospitalized COVID-19 patients, such as requirement of invasive mechanical ventilation and intensive care unit admission with high BMI/ Obesity was the chief outcome. While all-cause mortality in COVID-19 hospitalized patients with high BMI/ Obesity was the secondary outcome. Results: A total of 576,784 patients from 100 studies were included in this meta-analysis. Being obese was associated with increased risk of severe disease (RR=1.46, 95% CI 1.34-1.60, p<0.001, I2 = 92 %). Similarly, high mortality was observed in obese patients with COVID-19 disease (RR=1.12, 95% CI 1.06-1.19, p<0.001, I2 = 88%). In a multivariate meta-regression on severity outcome, the covariate of female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2= 50% of the between-study heterogeneity for severity. Similarly, for mortality outcome, covariate of female gender, proportion of pulmonary disease, diabetes, hypertension, and cardiovascular diseases were significant, these covariates collectively explained R2=53% of the between-study variability for mortality. Conclusions: Our findings suggest that obesity is significantly associated with increased severity and higher mortality among COVID-19 patients. Therefore, the inclusion of obesity or its surrogate body mass index in prognostic scores and streamlining the management strategy and treatment guidelines to account for the impact of obesity in patient care management is recommended.

A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients (preprint)

Importance/Background: Despite the global healthcare's exhaustive efforts to treat COVID-19, we still do not have an effective cure for it. Repurposing Ivermectin, a known antiparasitic agent, for treating COVID-19 has demonstrated positive results in several studies. We aim to evaluate the benefit and risk of Ivermectin in COVID-19. Methods: We conducted a systematic search for full-text manuscripts published from February 1, 2020 to March 27, 2021 that focused on efficacy and safety of Ivermectin therapy against COVID-19. The primary outcomes were overall mortality, need for intensive care unit (ICU) admission; secondary outcomes were - adverse effects, need for mechanical ventilation. Random-effects models were used for all analysis. Results: We included a total of 38 studies (n=15,002) in the qualitative analysis (Mortality N=28, ICU admission= 8, Mechanical Ventilation= 10, Adverse events=28) and out of these, 30 studies (n=11,291) were included in the quantitative analysis (Mortality N=22, ICU admission= 5, Mechanical Ventilation= 9, Adverse events=17). In the mortality meta-analysis, odds of death were lower in the Ivermectin-arm compared to the non-Ivermectin arm. (OR 0.39, 95% CI 0.22-0.70; I2=81%). Subgroup analysis of 12 randomized controlled trials with severity-based data showed mortality benefit overall (OR 0.33, 95% CI 0.15-0.72; I2=53%) and in the mild/moderate sub-group (OR 0.10, 95% CI 0.03-0.33; I2=0%). Benefit of Ivermectin in decreasing; the need for ICU admission (OR 0.48, 95% CI 0.17-1.37; I2=59%) and mechanical ventilation (OR 0.64, 95% CI 0.40-1.04; I2=17%) was not significant. The quantitative analysis of adverse effects with Ivermectin use was inconclusive (OR 0.92, 95% CI 0.64-1.33; I2=14%). Conclusion: Our meta-analysis suggests that Ivermectin could be an effective adjuvant therapy in reducing mortality, particularly in patients with mild-moderate clinical presentation of COVID-19. Trends of decreased need for ICU admissions and mechanical ventilation were observed but were not significant. The analysis for adverse effects was inconclusive.

Mortality and Severity in COVID-19 Patients on ACEIs & ARBs - A Meta-Regression Analysis (preprint)

Purpose: The primary objective of this review is to examine studies reporting association of mortality in COVID-19 patients with whether they were on Angiotensin-converting-enzyme inhibitors (ACEIs) and Angiotensin II receptor blockers (ARBs). A secondary objective is to similarly access associations with higher severity of the disease in COVID-19 patients. Materials and Methods: We searched multiple COVID-19 databases (WHO, CDC, LIT-COVID) for randomized trials and longitudinal studies from all over the world reporting mortality and severity published before January 18th, 2021. Meta-analyses were performed using 53 studies for mortality outcome and 43 for the severity outcome. Mantel-Haenszel odds ratios were generated to describe overall effect size using random effect models. To account for between study results variations, multivariate meta-Regression was performed with preselected covariates using maximum likelihood method for both the mortality and severity models. Result: Our findings showed that the use of ACEIs/ARBs did not significantly influence either mortality (OR=1.16 95% CI 0.94 to 1.44, p= 0.15, I2 = 93.2%) or severity (OR=1.18, 95% CI 0.94 to 1.48 p= 0.15, I2 = 91.1%) in comparison to not being on ACEIs/ARBs in COVID-19 positive patients. Multivariate meta-regression for the mortality model demonstrated that 36% of between study variations could be explained by differences in age, gender, and proportion of heart diseases in the study samples. Multivariate meta-regression for the severity model demonstrated that 8% of between study variations could be explained by differences in age, proportion of diabetes, heart disease and study country in the study samples. Conclusion: We found no association of mortality or severity in COVID-19 patients taking ACEIs/ARBs.