Riaz, Muhammad

Abstract Background Statins up-regulate angiotensin-converting enzyme 2, the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while also exhibiting pleiotropic antiviral, antithrombotic, and anti-inflammatory properties. Uncertainties exist about their effect on the course of SARS-CoV-2 infection. We sought to systematically review the literature and perform a meta-analysis to examine the association between prior statin use and outcomes of patients with coronavirus disease 2019 (COVID-19). Methods We searched Ovid Medline, Web of Science, Scopus, and the preprint server medRxiv from inception to December 2020. We assessed the quality of eligible studies with the Newcastle-Ottawa quality scale. We pooled adjusted relative risk (aRRs) of the association between prior statin use and outcomes of patients with COVID-19 using the DerSimonian-Laird random-effects model and assessed heterogeneity using the I2 index. Results Overall, 19 (16 cohorts and 3 case-control) studies were eligible, with a total of 395 513 patients. Sixteen of 19 studies had low or moderate risk of bias. Among 109 080 patients enrolled in 13 separate studies, prior statin use was associated with a lower risk of mortality (pooled aRR, 0.65 [95% confidence interval {CI}, .56–.77], I2 = 84.1%) and a reduced risk of severe COVID-19 was also observed in 48 110 patients enrolled in 9 studies (pooled aRR, 0.73 [95% CI, .57–.94], I2 = 82.8%), with no evidence of publication bias. Conclusions Cumulative evidence suggests that prior statin use is associated with lower risks of mortality or severe disease in patients with COVID-19. These data support the continued use of statins medications in patients with an indication for lipid-lowering therapy during the COVID-19 pandemic.

Abstract Objectives Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients. Methods We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization. Results Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96–1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00–1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19. Conclusions Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.

Purpose Open fractures are considered orthopedic emergencies that are traditionally treated with surgical debridement within 6 h of injury to prevent infection. However, this proclaimed “6-h rule” is arbitrary and not based on rigorous scientific evidence. The aim of our study was to systematically review the literature that compares late (>6 h from the time of injury) to early (<6 h from the time of injury) surgical debridement of pediatric open fractures. Methods We searched several databases from 1946 to 2013 for any observational or experimental studies that evaluated late and early surgical debridement of pediatric open fractures. We performed a meta-analysis using a random effects model to pool odds ratios for a comparison of infection rates between children undergoing late versus early surgical debridement. We also investigated the infection rates in upper- and lower-limb pediatric open fractures. Descriptive, quantitative, and qualitative data were extracted. Results Of the 12 articles identified, three studies (retrospective cohort studies) were eligible for the meta-analysis, encompassing a total of 714 open fractures. The pooled odds ratio (OR = 0.79) for infection between late and early surgical debridement was in favor of late surgical debridement but was not statistically significant (95 % CI 0.32, 1.99; p = 0.38, I 2 = 0 %). No significant difference in infection rate was detected between pediatric open fractures in the upper and lower limbs according to the time threshold in the included studies (OR = 0.72, 95 % CI 0.29, 1.82; p = 0.40, I 2 = 0 %). Conclusions The cumulative evidence does not, at present, indicate an association between late surgical debridement and higher infection rates in pediatric open fractures. However, initial expedient surgical debridement of open fractures in children should always remain the rule. Thus, multi-center randomized controlled trials or prospective cohort studies will be able to answer this question with more certainty and a higher level of evidence. Level of evidence Level III.