Antiviral and anti-inflammatory drugs to combat COVID-19: Effects on cardiac ion channels and risk of ventricular arrhythmias.

Introduction: Drugs with no indication for the treatment of cardiovascular diseases (e.g., drugs employed to treat COVID-19) can increase the risk of arrhythmias. Of interest, a six-fold increase in the number of arrhythmic events was reported in patients with severe COVID-19. In this study, we reviewed (i) the pro-arrhythmic action of drugs given to patients with COVID-19 infection, and (ii) the effects of inflammatory cytokines on cardiac ion channels and possible generation of arrhythmias. Methods: We conducted a literature search on the drugs with purported or demonstrated efficacy against COVID-19 disease, emphasizing the mechanisms by which anti-COVID-19 drugs and inflammatory cytokines interfere with cardiac ion channels. Results: Antibiotics (azithromycin), antimalarials (hydroxychloroquine, chloroquine), antivirals (ritonavir/lopinavir, atazanavir), and some of the tyrosine kinase inhibitors (vandetanib) could induce long QT and increase risk for ventricular arrhythmias. The pro-arrhythmic action results from drug-induced inhibition of Kv11.1 (hERG) channels interfering with the repolarizing potassium IKr currents, leading to long QT and increased risk of triggered arrhythmias. At higher concentrations, these drugs may interfere with IKs, IK1, and/or Ito potassium currents, and even inhibit sodium (INa) and calcium (ICa) currents, inducing additional cardiac toxicity. Ibrutinib, an inhibitor of Bruton's TK, increased the incidence of atrial fibrillation and ventricular tachycardia associated with a short QT interval. Inflammatory cytokines IL-6 and TNF-α inhibit IKr and Ito repolarizing potassium currents. High levels of inflammatory cytokines could contribute to the arrhythmic events. For remdesivir, favipiravir, dexamethasone, tocilizumab, anakinra, baricitinib, and monoclonal antibodies (bamlanivimab, etesevimab, and casirivimab), no evidence supports significant effects on cardiac ion channels, changes in the QT interval, and increased risk for ventricular arrhythmias. Conclusion: This study supports the concept of hERG channel promiscuity. Different drug classes given to COVID-19 patients might delay repolarization, and increase the risk of ventricular arrhythmias. The presence of comorbid pro-arrhythmic disease states, and elevated levels of pro-arrhythmic cytokines, could increase the risk of ventricular arrhythmias. Discontinuation of nonessential drugs and correction of electrolyte abnormalities could prevent severe ventricular arrhythmias. Altogether, the most effective therapies against COVID-19 (remdesivir, dexamethasone, monoclonal antibodies) lack pro-arrhythmic activity.

Impact of pharmacy-supported interventions on proportion of patients receiving non-indicated acid suppressive therapy upon discharge: A systematic review and meta-analysis.

OBJECTIVE: Conduct a systematic review and meta-analysis to estimate the impact of pharmacy-supported interventions on the proportion of patients discharged from the hospital on inappropriate acid suppressive therapy (AST). METHODS: To identify studies, the following databases were systematically searched on October 14th, 2018 and repeated on September 12th, 2019: Ovid MEDLINE(R) and In-Process & Other Non-Indexed Citations and Daily, Embase.com, CINAHL, Web of Science, Cochrane CENTRAL (EBSCO), and ClinicalTrials.gov. Eligible studies consisted of adults, intervention and historical/usual care groups, description of active pharmacy-supported intervention, and proportion of patients discharged on inappropriate AST. Qualitative assessments and quantitative analyses were performed. Modified funnel plot analysis assessed heterogeneity. Preferred reporting items of systematic reviews and meta-analyses (PRISMA) methodology was used to evaluate studies in this review. RESULTS: Seventeen publications resulting in 16 studies were included in the review. Using random effects model, meta-analysis showed a significant reduction in the odds of being discharged on inappropriate AST from the hospital in the pharmacist-supported intervention arm versus comparator (Odds Ratio 0.33 [95%CI 0.20 to 0.53]), with significant heterogeneity (I2 = 86%). Eleven studies favored pharmacy-supported interventions, four were inconclusive and one favored usual care. Using modified funnel plot analysis, our final evaluation was distilled to 11 studies and revealed a similar outcome (OR 0.36 [95%CI 0.27 to 0.48]), but with less heterogeneity (I2 = 36%). CONCLUSION: This systematic review and meta-analysis showed that pharmacy-supported interventions were associated with a significantly reduced probability of patients discharged on inappropriate AST. However, heterogeneity was high and may affect interpretation of results. Using funnel plot optimization method, three positive and two negative studies were objectively removed from analyses, resulting in a similar effect size, but with less heterogeneity. To improve study quality, future researchers should consider utilizing a pre-post, multi-arm, prospective design with sampling randomization, training of data extractors (preferably two extractors), re-evaluating a small dataset to check for agreement and providing a comprehensive methodology in subsequent publications.

Using resident health advocates to improve public health screening and follow-up among public housing residents, Boston, 2007-2008.

INTRODUCTION: Promoting screening for hypertension, high cholesterol, diabetes, and dental disease, particularly among residents of public housing, is a key strategy for achieving the objectives of Healthy People 2010. This community-based participatory research study tested a resident health advocate (RHA) intervention in public housing to increase use of mobile screening and to assess postscreening follow-up care for people with positive screening results. METHODS: During the summers of 2007 and 2008, a mobile health unit screened residents at 4 housing developments for hypertension, high cholesterol, diabetes risk, and dental disease. In the first summer, at 2 intervention sites, RHAs used personal contacts and repeated flyers to recruit residents; 2 control sites received standard recruitment, which was to leave flyers with the development manager. In the second summer, the 2 control sites from the previous year became intervention sites. For both summers combined, we calculated the number of people at intervention and control sites who used the van and we examined rates of appointments made and kept for residents who had positive screening test results. RESULTS: Screening rates were higher in the intervention condition compared with the control condition (relative risk [RR], 1.55; 95% confidence interval [CI], 1.12-2.15). Approximately 65% of participants screened positive for at least 1 condition. The proportion of participants with screen-positive findings who had follow-up appointments increased from 15% in 2007 to 55% in 2008. CONCLUSION: The use of RHAs increased participation in health screening among public housing residents and rates of follow-up medical visits for people with positive screening results.