Objective This living, systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of macrolides for treating patients with COVID-19. Design A living, systematic review. Database We conducted searches in the centralized repository L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from the Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customized to group all COVID-19 evidence in one place. Today it is maintained through regular searches in 39 databases. Methods We included randomized trials evaluating the effect of macrolides — as monotherapy or in combination with other drugs — versus placebo or no treatment in patients with COVID-19. Randomized trials evaluating macrolides in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomized studies in COVID-19 were searched in case we found no direct evidence from randomized trials. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. Measures included all-cause mortality; the need for invasive mechanical ventilation; extracorporeal membrane oxygenation, length of hospital stay, respiratory failure, serious adverse events, time to SARS-CoV-2 RT-PCR negativity. We applied the GRADE approach to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates. Results The search in the L·OVE platform retrieved 424 references. We considered 260 as potentially eligible and were reviewed in full texts. We included one randomized clinical trial that evaluated the use of azithromycin in combination with hydroxychloroquine compared to hydroxychloroquine alone in hospitalized patients with COVID 19. The estimates for all outcomes evaluated resulted in insufficient power to draw conclusions. The quality of the evidence for the main outcomes was low to very low. Conclusions Macrolides in the management of patients with COVID 19 showed no beneficial effects compared to standard of care. The evidence for all outcomes is inconclusive. Larger trials are needed to determine the effects of macrolides on pulmonary and other outcomes in COVID-19 patients. Systematic review registration PROSPERO Registration number: CRD42020181032 Protocol preprint DOI: 10.31219/osf.io/rvp59

The increasing amount of evidence has caused an increasing amount of literature reviews. There are different types of reviews —systematic reviews are the best known—, and every type of review has different purposes. The scoping review is a recent model that aims to answer broad questions and identify and expose the available evidence for a broader question, using a rigorous and reproducible method. In the last two decades, researchers have discussed the most appropriate method to carry out scoping reviews, and recently the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ for scoping reviews (PRISMA-ScR) reporting guideline was published. This is the fifth article of a methodological collaborative series of narrative reviews about general topics on biostatistics and clinical epidemiology. This review aims to describe what scoping reviews are, identify their objectives, differentiate them from other types of reviews, and provide considerations on how to carry them out.

This is the second article from a collaborative methodological series of biostatistics and clinical epidemiology narrative reviews. This review aims to describe living systematic reviews’ relevance, the considerations that should be taken when producing one, and the challenges proper of this type of review. The living systematic review is a continuous update that maintains a systematic review’s rigor and methodological quality. The living format is appropriate when the review aims to answer a priority question in terms of health decision-making, the existent certainty of the evidence for this question is low or very low, and new evidence will likely appear soon. To carry out a successful living systematic review, researchers should consider different things, such as: having a continuous and automated search, having update criteria, evaluating how to update the meta-analysis and how to perform the editorial process, and publishing in a friendly format, among others. As living systematic reviews are a new proposal, they will likely change in the future to improve their performance, so we will have to keep an eye on its future updates.

ObjectiveThis living systematic review aims to provide a timely, rigorous and continuously updated summary of the evidence available on the role of macrolides for the treatment of patients with COVID-19.Data sources We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal.Eligibility criteria for selecting studies and methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomised trials evaluating the effect of macrolides — as monotherapy or in combination with other drugs — versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating macrolides in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case we find no direct evidence from randomised trials, or if the direct evidence provides low- or very low-certainty for critical outcomes.Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the GRADE system to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates.Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.PROSPERO Registration number CRD42020181032

BackgroundDiabetic macular oedema (DME) is a worldwide major cause of low vision and blindness. Intravitreal antivascular endothelial growth factor (anti-VEGF) constitutes an effective treatment. Clinical practice guidelines (CPGs) are synthesis documents that seek to improve patient care.ObjectivesTo identify CPGs that make anti-VEGF recommendations for DME and to assess their reporting quality and their considerations when making recommendations.Eligibility criteriaCPGs published between December 2009 and December 2019 that make explicit anti-VEGF recommendations in DME.Sources of evidenceSensitive search strategy in Embase, Google Scholar and hand-searching on 165 websites.MethodsWe extracted information from each CPG with a previously piloted sheet. Two independent authors applied theAppraisal of Guidelines, Research and Evaluation tool (AGREE-II) assessment for each CPG.ResultsThe 21 included CPGs recommend anti-VEGF for DME, but there is a wide variation among the clinical aspects included, such as location of DME, visual acuity required, therapeutical alternatives or discontinuation. Most have a poor quality of reporting based on the AGREE-II tool assessment, especially those developed by ophthalmological societies, those that have an exclusive content about DME, and those where most of their authors disclose conflict of interest (COI) with pharmaceutical industry or where their authors did not report COIs. Pharmaceutical-sponsored CPGs did not use systematic reviews (SRs) to support their recommendations. Very few recommendations consider patient values and preferences, equity, acceptability and feasibility of the intervention.ConclusionsMost of the CPGs that made recommendations of anti-VEGF for DME have poor quality of reporting, do not use SRs and do not consider patients’ values and preferences.