The COVID-19 pandemic began in early 2020 with major health consequences. While a need to disseminate information to the medical community and general public was paramount, concerns have been raised regarding the scientific rigor in published reports. We performed a systematic review to evaluate the methodological quality of currently available COVID-19 studies compared to historical controls. A total of 9895 titles and abstracts were screened and 686 COVID-19 articles were included in the final analysis. Comparative analysis of COVID-19 to historical articles reveals a shorter time to acceptance (13.0[IQR, 5.0–25.0] days vs. 110.0[IQR, 71.0–156.0] days in COVID-19 and control articles, respectively; p < 0.0001). Furthermore, methodological quality scores are lower in COVID-19 articles across all study designs. COVID-19 clinical studies have a shorter time to publication and have lower methodological quality scores than control studies in the same journal. These studies should be revisited with the emergence of stronger evidence.

Topical drug delivery to the front of the eye is extremely inefficient due to effective natural protection mechanisms such as precorneal tear turnover and the relative impermeability of the cornea and sclera tissues. This causes low ocular drug bioavailability, requiring large frequent doses that result in high systemic exposure and side effects. Mucoadhesive drug delivery systems have the potential to improve topical drug delivery by increasing pharmaceutical bioavailability on the anterior eye surface. We report the synthesis and characterization of a series of poly(L-lactide)-b-poly(methacrylic acid-co-3-acrylamidophenylboronic acid) block copolymer micelles for use as mucoadhesive drug delivery vehicles. Micelle properties, drug release rates, and mucoadhesion were shown to depend on phenylboronic acid content. The micelles showed low in vitro cytotoxicity against human corneal epithelial cells and undetectable acute in vivo ocular irritation in Sprague-Dawley rats, suggesting good biocompatibility with the corneal surface. The micelles show the potential to significantly improve the bioavailability of topically applied ophthalmic drugs, which could reduce dosage, frequency of administration, and unintentional systemic exposure. This would greatly improve the delivery of the ocular drugs such as the potent immunosuppressive cyclosporine A used in the treatment of severe dry eye disease.

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Objective: To systematically evaluate the quality of reporting of currently available COVID-19 studies compared to historical controls. Design: A systematic review and case-control analysis Data sources: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials until May 14, 2020 Study selection: All original clinical literature evaluating COVID-19 or SARS-CoV2 were identified and 1:1 historical control of the same study type in the same published journal was matched from the previous year Data extraction: Two independent reviewers screened titles, abstracts, and full-texts and independently assessed methodological quality using Cochrane Risk of Bias Tool, Newcastle-Ottawa Scale, QUADAS-2 Score, or case series checklist. Results: 9895 titles and abstracts were screened and 686 COVID-19 articles were included in the final analysis in which 380 (55.4%) were case series, 199 (29.0%) were cohort, 63 (9.2%) were diagnostic, 38 (5.5%) were case-control, and 6 (0.9%) were randomized controlled trials. Overall, high quality/low-bias studies represented less than half of COVID-19 articles - 49.0% of case series, 43.9% of cohort, 31.6% of case-control, and 6.4% of diagnostic studies. We matched 539 control articles to COVID-19 articles from the same journal in the previous year for a final analysis of 1078 articles. The median time to acceptance was 13.0 (IQR, 5.0-25.0) days in COVID-19 articles vs. 110.0 (IQR, 71.0-156.0) days in control articles (p<0.0001). Overall, methodological quality was lower in COVID-19 articles with 220 COVID-19 articles of high quality (41.0%) vs. 392 control articles (73.3%, p<0.0001) with similar results when stratified by study design. In both unadjusted and adjusted logistic regression, COVID-19 articles were associated with lower methodological quality (odds ratio, 0.25; 95% CI, 0.20 to 0.33, p<0.0001). Conclusion: Currently published COVID-19 studies were accepted more quickly and were found to be of lower methodological quality than comparative studies published in the same journal. Given the implications of these studies to medical decision making and government policy, greater effort to appropriately weigh the existing evidence in the context of emerging high-quality research is needed. Study registration: PROSPERO: CRD42020187318

BackgroundWe sought to determine the prognostic value of transthoracic echocardiography (TTE)-derived right ventricular dysfunction (RVD) in haemodynamically stable and intermediate-risk patients with acute pulmonary embolism (PE), evaluate continuous RVD parameters, and assess the literature quality.MethodsWe searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for studies assessing TTE-derived RVD in haemodynamically stable PE that reported in-hospital adverse events within 30 days. We determined pooled odds ratios (ORs) using a random-effects model, created funnel plots, evaluated the Newcastle–Ottawa scale and performed Grading of Recommendations, Assessment, Development and Evaluation.ResultsBased on 55 studies (17 090 patients, 37.8% RVD), RVD was associated with combined adverse events (AEs) (OR 3.29, 95% confidence interval (CI) 2.59–4.18), mortality (OR 2.00, CI 1.66–2.40) and PE-related mortality (OR 4.01, CI 2.79–5.78). In intermediate-risk patients, RVD was associated with AEs (OR 1.99, CI 1.17–3.37) and PE-related mortality (OR 6.16, CI 1.33–28.40), but not mortality (OR 1.63, CI 0.76–3.48). Continuous RVD parameters provide a greater spectrum of risk compared to categorical RVD. We identified publication bias, poor methodological quality in 34/55 studies and overall low certainty of evidence.ConclusionsRVD is frequent in PE and associated with adverse outcomes. However, data quality and publication bias are limitations of existing evidence.