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The efficacy of services for children and adolescents with obesity is well researched, but this review describes what actually matters to stakeholders (children, caregivers, and professionals) in relation to such services.A mega-ethnography, an innovative review-of-reviews approach that uses conceptual findings as primary data, was performed. Twelve bibliographic databases (2010-2020) were searched for reviews that considered the values and preferences of stakeholders concerning services or interventions (diet, exercise, lifestyle) that targeted children and adolescents with obesity.From 485 citations, 17 relevant reviews were identified. The synthesis found that the perceived need to address obesity is determined by subjective norms of weight and interactions with health professionals. Children's and caregivers' participation in obesity management services is shaped by their response to content, acceptability, and perceived benefits and demands. Whether they continue with and complete an intervention are determined by its perceived success, beyond just weight loss, including behavior change, enhanced self-esteem, and the provision of timely and relevant support.Obesity management services must be promoted in a sensitive manner and must be tailored, be varied, and make positive use of family and schools if children and caregivers are to seek and actively engage with them.

To evaluate reporting of minimal important difference (MID) estimates using anchor-based methods for patient-reported outcome measures (PROMs), and the association with reporting deficiencies on their credibility.Systematic survey of primary studies empirically estimating MIDs. We searched Medline, EMBASE, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database until October 2018. We evaluated study reporting, focusing on participants' demographics, intervention(s), characteristics of PROMs and anchors, and MID estimation method(s). We assessed the impact of reporting issues on credibility of MID estimates.In 585 studies reporting on 5,324 MID estimates for 526 distinct PROMs, authors frequently failed to adequately report key characteristics of PROMs and MIDs, including minimum and maximum values of PROM scale, measure of variability accompanying the MID estimate and number of participants included in the MID calculation. Across MID estimates (n = 5,324), the most serious reporting issues impacting credibility included infrequent reporting of the correlation between the anchor and PROM (66%), inadequate details to judge precision of MID point estimate (13%), and insufficient information about the threshold used to ascertain MIDs (16%).Serious issues of incomplete reporting in the MID literature threaten the optimal use of MID estimates to inform the magnitude of effects of interventions on PROMs.

We conceptualize patient values and preferences as the relative importance of health outcomes (RIO) which are often obtained through utility elicitation research. A transparent and structured approach to present synthesized RIO evidence and the certainty of this evidence is needed. This study aims to adapt the summary of findings (SoF) table to describe the RIO.We performed three interactive workshops with a protype version of the SoF table for RIO, evidence adapted from the SoF table for intervention effects. We then tested the new format through semi-structured interviews with professionals who interpret RIO evidence (e.g., systematic review authors and guideline developers).We adapted the SoF table for the presentation of RIO evidence. This SoF table may be easy to use, but bears one risk: some participants misunderstood the utility information and the variability around the RIO. We added a visual analogue scale to clarify the concept of utilities.Through a multi-stage process including brainstorming sessions and interviews, we adapted the SoF table to present RIO evidence. This table may enhance understanding of evidence synthesis of values and preferences, facilitating the incorporation of this type of evidence in decision-making.

Objectives The objective of the study was to develop an inventory summarizing all anchor-based minimal important difference (MID) estimates for patient-reported outcome measures (PROMs) available in the medical literature. Study Design and Setting We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database internal library (January 1989–October 2018). We included primary studies empirically calculating an anchor-based MID estimate for any PROM in adults and adolescents. Pairs of reviewers independently screened and selected studies, extracted data, and evaluated the credibility of the MIDs. Results We identified 585 eligible studies, the majority conducted in Europe (n = 211) and North America (n = 179), reporting 5,324 MID estimates for 526 distinct PROMs. Investigators conducted their studies in the context of patients receiving surgical (n = 105, 18%), pharmacological (n = 85, 15%), rehabilitation (n = 65, 11%), or a combination of interventions (n = 194, 33%). Of all MID estimates, 59% (n = 3,131) used a global rating of change anchor. Major credibility limitations included weak correlation (n = 1,246, 23%) or no information regarding the correlation (n = 3,498, 66%) between the PROM and anchor and imprecision in the MID estimate (n = 2,513, 47%). Conclusion A large number of MIDs for assisting in the interpretation of PROMs exist. The MID inventory will facilitate the use of MID estimates to inform the interpretation of the magnitude of treatment effects in clinical research and guideline development.

IntroductionThe prevalence of COVID-19 and its impact varied between countries and regions. Pregnant women are at high risk of COVID-19 complications compared with non-pregnant women. The magnitude of variations, if any, in SARS-CoV-2 infection rates and its health outcomes among pregnant women by geographical regions and country’s income level is not known.MethodsWe performed a random-effects meta-analysis as part of the ongoing PregCOV-19 living systematic review (December 2019 to April 2021). We included cohort studies on pregnant women with COVID-19 reporting maternal (mortality, intensive care admission and preterm birth) and offspring (mortality, stillbirth, neonatal intensive care admission) outcomes and grouped them by World Bank geographical region and income level. We reported results as proportions with 95% confidence intervals (CI).ResultsWe included 311 studies (2 003 724 pregnant women, 57 countries). The rates of SARS-CoV-2 infection in pregnant women varied significantly by region (pConclusionThe rates of SARS-CoV-2 infection in pregnant women vary globally, and its health outcomes mirror the COVID-19 burden and global maternal and offspring inequalities.PROSPERO registration numberCRD42020178076.

WHAT IS KNOWN ON THE SUBJECT?: It is generally accepted that all interventions carried out by mental health nurses involve engagement with the patient; this engagement is a process that is gradually constructed and is not immediate. In Spain during last decade, nurses working in assertive outreach teams have gradually replaced the traditional institutional setting in favour of environments that are more familiar to the patient. In contrast, when patients and nurses interact outside institutional settings, a new approach and skillset is required in order to adapt to the new environment. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: We have systematically identified and assessed the available evidence on how nurses work in assertive outreach team programmes. The therapeutic link is not just assistance; it is actually a construct, which is established between nurse and patient, with the aim of favouring, fostering and strengthening the therapeutic relationship. Only a few studies have discussed the nurse-patient therapeutic link in assertive outreach services. However, it seems important that nurses use a standardized language, that is, a language promoted as a model of correct use and used for functions of greater prestige, especially in public administration and teaching, to integrate it into the theoretical framework. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: With the synthesis that we present, we hope that it promote a more consistent use of the engagement concept in research on this topic. In turn, this will enhance staff support and training and will foster evidence-based practice. The conceptualization of nursing language and its use by professionals helps to improve practice and the lack of a theoretical framework with a nurse perspective. It is necessary to establish a consensus between mental health nurses around the engagement' meaning in the programmes of assertive outreach teams. ABSTRACT: Introduction During last decade in Spain, nurses working in assertive outreach programmes have replaced the traditional institutional setting in favour of the patient's own environment. Engagement with patients requires a different skillset when the axis of the nurse-patient interaction is the patient's own environment. The engagement alone could be associated with the innate concept of patient's care and the helping relationship. However, in the individualized care models, the engagement seems to be an instrument with its own characteristics for the purpose of providing mental health care. Aim/Question To systematically identify and assess the empirical evidence on the relationships and engagement between patients with mental illness (schizophrenia, psychotic disorders, schizoaffective disorders, mood disorders and disorders of adult personality) and nursing mental health nurses. Method Systematic literature review based on PRISMA guidance. Results We identified and reviewed seven primary research studies. Following the analytic processes, three themes emerged: existence of different engagement levels, training needs and skills in the creation and consolidation of the engagement, and engagement as process. Discussion The engagement of nurse and patient is understood as a process that incorporates different stages. Whilst it is established, the engagement is subject to positive and negative influences. For the creation of the engagement and its maintenance specialized skills, knowledge and personal attributes (resilience, psychosocial skills, compressive knowledge of mental health illnesses, capacity to build effective relationships, adaptability and problem-solving) are necessary, but the main focus is on context where it develops, selected by the patient himself, for example, his home. Implications for Practice Administrators may have questions about appropriate hiring practices for assertive outreach teams since certain skills are necessary to obtain un engagement process, and staff training should be considered a key issue to provide specific skills for enhancing engagement and the therapeutic relationship. Conclusion The engagement must be understood as a long-term process. For the creation of the engagement and its maintenance, specialized skills, knowledge and personal attributes are necessary.

Infants exposed to Zika virus (ZIKV) or diagnosed with congenital Zika syndrome (CZVS) may present dysphagia, regurgitation and other feeding difficulties. They may require special feeding practices to minimise the risk of mortality, morbidity and developmental problems. Improving knowledge, skills and behaviours of caregivers may preserve health, maximise development and promote quality of life among affected infants. We reviewed intervention studies of modified feeding practices and additional primary caregiver support to improve outcomes among infants 0 to 12 months of age exposed to ZIKV or diagnosed with CZVS.Rapid review and meta-analysis. We searched PubMed/MEDLINE and contacted experts. The search is current to 18 July 2020. We planned a meta-analysis using fixed-effect models; if unfeasible, we intended to summarise studies narratively. We planned to assess risk of bias of included studies and quality of evidence using Cochrane guidance.We identified 42 records for title and abstract screening; 14 were eligible for full-text assessment. Among these, no intervention studies were found. Eight observational studies reported on the nutritional status, feeding practices and outcomes among infants affected by ZIKV or diagnosed with CZVS. They are presented and discussed to provide a basis for future research.While no intervention studies were found, evidence from eight observational studies highlights the need for early nutrition interventions and caregiver support among infants affected by ZIKV or diagnosed with CZSV. More research is needed to assess whether modifications of feeding practices and provision of additional primary caregiver support will impact outcomes of interest.Les nourrissons exposés au virus Zika (VZIK) ou diagnostiqués avec le syndrome congénital Zika (SCZ) peuvent présenter une dysphagie, des régurgitations et d'autres difficultés d'alimentation. Ils peuvent nécessiter des pratiques alimentaires spéciales pour minimiser le risque de mortalité, de morbidité et de problèmes de développement. L'amélioration des connaissances, des compétences et des comportements des soignants peut préserver la santé, maximiser le développement et promouvoir la qualité de vie des nourrissons affectés. Nous avons examiné les études d'intervention sur les pratiques d'alimentation modifiées et le soutien additionnel aux principaux soignants pour améliorer les résultats chez les nourrissons de 0 à 12 mois exposés au VZIK ou diagnostiqués avec le SCZ. MÉTHODES: Revue rapide et méta-analyse. Nous avons effectué des recherches dans PubMed/MEDLINE et contacté des experts. La recherche a été mise à jour au 18 juillet 2020. Nous avons prévu une méta-analyse utilisant des modèles à effets fixes; si cela n’était pas réalisable, nous avions l'intention de résumer les études de manière narrative. Nous avons prévu d'évaluer le risque de biais des études incluses et la qualité des données en utilisant les directives Cochrane. RÉSULTATS: Nous avons identifié 42 reports pour la recherche des titres et des résumés; 14 étaient éligibles pour une évaluation en texte intégral. Parmi ceux-ci, aucune étude d'intervention n'a été trouvée. Huit études observationnelles ont rapporté sur l'état nutritionnel, les pratiques d'alimentation et les résultats chez les nourrissons atteints du VZIK ou diagnostiqués avec le SCZ. Elles sont présentées et discutées pour fournir une base pour les futures recherches.Bien qu'aucune étude d'intervention n'ait été trouvée, les données de huit études observationnelles mettent en évidence la nécessité d'interventions nutritionnelles précoces et de soutien des soignants des nourrissons atteints de VZIK ou diagnostiqués avec le SCZ. Des recherches supplémentaires sont nécessaires pour évaluer si les modifications des pratiques d'alimentation et la fourniture d'un soutien additionnel aux principaux soignants auront un impact sur les résultats d'intérêt.

Recommendations for preventing and diagnosing recurrent urinary tract infection (UTI) tend to vary between clinical practice guidelines (CPGs) because of low-quality scientific evidence, potentially leading to practice variation and suboptimal care. We assessed the quality of existing CPGs for recurrent UTI.A systematic search was performed from January 2000 to June 2021 in PubMed and EMBASE for CPGs on recurrent UTI prevention or hospital diagnostics in Dutch, English, and Spanish. Each CPG was assessed by four appraisers in a multidisciplinary review team, using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) instrument.We identified and assessed eight CPGs published between 2013 and 2021. The scope and purpose (mean and standard deviation: 67.3 ± 21.8) and clarity of presentation (74.8 ± 17.6) domains scored highly. However, issues with methods, patient participation, conflict of interests, and facilitators and barriers were common and resulted in lower scores for the rigour of development (56.9 ± 25.9), applicability (19.6 ± 23.4), stakeholder involvement (50.4 ± 24.6), and editorial independence (62.1 ± 23.1) domains. Overall, two CPGs were recommended, three were recommended with modifications, and three were not recommended.Significant room for improvement exists in the quality of CPGs for recurrent UTI, with most displaying serious limitations in the stakeholder involvement, rigour of development, and applicability domains. These aspects must be improved to decrease diagnostic and therapeutic uncertainty. Developers could benefit from using checklists and following guidelines when developing de novo CPGs.

Background Vitamin D has been widely promoted for bone health through supplementation and fortification of the general adult population. However, there is growing evidence that does not support these strategies. Our aim is to review the quality and recommendations on vitamin D nutritional and clinical practice guidelines and explore predictive factors for their direction and strength. Methods We searched three databases and two guideline repositories from 2010 onwards. We performed a descriptive analysis, a quality appraisal using AGREE II scores (Appraisal of Guidelines Research and Evaluation) and a bivariate analysis evaluating the association between direction and strength of recommendations, AGREE II domains' scores and pre-specified characteristics. Results We included 34 guidelines, 44.1% recommended, 26.5% suggested, and 29.4% did not recommend vitamin D supplementation. Guidelines that scored higher for "editorial independence" and "overall quality score" were less likely to recommend or suggest vitamin D supplementation (median 68.8 vs. 35.4; p=0.001), and median 58.3 vs. 37.5; p=0.02). Guidance produced by government organizations and those that reported source of funding were associated with higher AGREE II scores. Unclear role of source of funding was associated with recommending or suggesting vitamin D supplementation (p=0.034). Editorial independence was an independent predictor for recommending or suggesting vitamin D supplementation (OR 1.09; CI95% 1.02 to 1.16; p=0.006). Conclusions Policymakers, clinicians and patients should be aware that lower quality guidelines, and those reporting conflicts of interest are more likely to promote vitamin D supplementation. Guideline organizations should improve the quality of their recommendations' development and the management of conflicts of interest. Users and editors should be aware of these findings when using and appraising guidelines.

Introduction: Long-term care encompasses a wide range of health and social services that are delivered in different settings. Long-term care is susceptible to fragmentation in service delivery: during needs assessments, accessing benefits, data collection and in the diversity of quality improvement efforts. The aim of this work was to develop a toolkit for guiding the design, development and reporting of country assessments on the integrated delivery of health and social services for long-term care. Methods: This toolkit is based on the principles of systems thinking, people-centeredness and integrated care, life-course approach, healthy ageing, human rights and gender perspective. The underpinning conceptual framework is the European Framework for Action on Integrated Health Service Delivery. The toolkit benefited from the input of professionals in the field of long-term care and from existing resources for fostering the delivery of integrated care for older people. There were complementary scientific and grey literature searches on long-term care research and assessments in Europe. The toolkit was piloted in six country studies for validation and adaptation to fieldwork. Results: The toolkit is designed along four domains: individual and population needs, performance measures, long-term care service delivery and system enablers. The toolkit outlines a standard process for country assessment, consisting of: i) initial desk research, ii) country visit preparation, iii) country visit completion, iv) analysis of data and evidence and v) reporting of findings. The toolkit includes a checklist of items that should be covered during the initial desk research, as well as measures and outcomes for each item and detailed “where-to-look” information. Country site visits consists of three activities: i) individual and group interviews, ii) site visits and iii) workshops and focus groups. Data analysis focuses on comparing the needs of the older people against the performance measures and the overall services delivery adopting, to the extent possible, a gender and human rights perspective. The toolkit was implemented in Croatia, Denmark, Germany, Portugal, Romania and Turkey. Discussion: The toolkit can serve as blueprint to identify challenges and facilitators in pursuing integrated delivery of long-term care. The toolkit is pragmatic and can be adapted depending on whether the country assessment is initiated by local governments, international agencies, academia or services providers. Conclusions: Promoting the availability and quality of long-term care services that are integrated, people-centred and properly managed is a right step for ensuring healthy lives and wellbeing in the old age. The overall aim of this toolkit is contributing to this endeavour. Lessons learned: The country assessment results will be instrumental to inform evidence-based policy recommendations that will help countries optimise existing long-term care systems and to inform the development of emerging ones. Limitations: The Toolkit did not undergo a formal validation process. Nevertheless, general feedback from stakeholders involved in the development was positive. Feasibility and acceptability of the toolkit were adequate during the country assessments. Suggestions for future research: The toolkit could be further refined based on the results of future country assessments.

Objectives The purpose of this research was to generate and validate a questionnaire that identifies determinants of guideline use from the clinician perspective. Study Design and Setting From January 2017 to March 2018, a seven-member six-country multidisciplinary team used a five-step multimethod design to search for and compile determinant frameworks, map items to determinants (content validity), select the best items for each determinant (content validity), refine wording of determinants and items (face validity), merge or separate items (construct validity), and review the final questionnaire. Results The Clinician Guideline Determinants Questionnaire includes four sections: clinician demographic information (including two determinants: attitudes about/experience with guidelines), 26 close-ended items reflecting clinician- and guideline-specific determinants, four open-ended items reflecting enablers and barriers perceived as most important, and three items on learning style (preferred sources of guideline information). Conclusion The Clinician Guideline Determinants Questionnaire is a comprehensive, validated instrument that addresses multiple potential determinants specific to guideline use from a clinician perspective. The Questionnaire can be used at multiple time points in the guideline development cycle to assess determinants of the use of new, updated, or adapted guidelines and before and after interventions to assess their impact on the determinants of guideline use. In future research, we will establish psychometric properties of the new questionnaire.

Objectives The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group defines patient values and preferences as the relative importance patients place on the main health outcomes. We provide GRADE guidance for assessing the risk of bias and indirectness domains for certainty of evidence about the relative importance of outcomes. Study Design and Setting We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance and consulted GRADE members and other stakeholders for feedback. Results This is the first of two articles. A body of evidence addressing the importance of outcomes starts at “high certainty”; concerns with risk of bias, indirectness, inconsistency, imprecision, and publication bias lead to downgrading to moderate, low, or very low certainty. We propose subdomains of risk of bias as selection of the study population, missing data, the type of measurement instrument, and confounding; we have developed items for each subdomain. The population, intervention, comparison, and outcome elements associated with the evidence determine the degree of indirectness. Conclusion This article provides guidance and examples for rating the risk of bias and indirectness for a body of evidence summarizing the importance of outcomes.

Purpose Soft tissue sarcomas are a heterogeneous group of rare tumours of mesenchymal origin. Evidence mapping is one of the most didactic and friendly approaches to organise and summarise the range of research activity in broad topic fields. The objective of this evidence mapping is to identify, describe and organise the current available evidence about therapeutic interventions on soft tissues sarcomas. Methods We followed the methodology of global evidence mapping. We performed a search of the PubMed, EMBASE, The Cochrane Library and Epistemonikos to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two independent literature reviewers assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and used tables and a bubble plot to display the results. Results The map is based on 24 SRs that met eligibility criteria and included 66 individual studies. Three-quarters were either observational or uncontrolled clinical trials. The quality of the included SRs was in general moderate or high. We identified 64 PICO questions from them. The corresponding results mostly favoured the intervention arm. Conclusions This evidence mapping was built on the basis of SRs, which mostly included non-experimental studies and were qualified by the AMSTAR tool as of moderate quality. The evidence mapping created from PICO questions is a useful approach to describe complex and huge clinical topics through graphical media and orientate further research to fulfil the existing gaps. However, it is important to delimitate the steps of the evidence mapping in a pre-established protocol.

Objectives To identify, describe, and map contemporary nutrition guidelines (NGs) from reviews that used the Appraisal of Guidelines, Research and Evaluation (AGREE) tool. Study Design and Setting We performed an overview of reviews that systematically assessed the quality of NGs using the AGREE tool. We searched MEDLINE and EMBASE from inception to February 2018. Two authors independently selected and assessed reviews and extracted data. Results We included nine evaluations with a total of 67 NGs. The higher median AGREE scores were for the domains “scope and purpose” (80%, Q1–Q3: 59–89%) and “clarity and presentation” (69%, Q1–Q3: 53–89%), while the lower were for “rigor of development” (58%, Q1–Q3: 31–84%), “editorial independence” (53%, Q1–Q3: 19–79%), “stakeholder involvement” (50%, Q1–Q3: 28–72%), and “applicability” (22%, Q1–Q3: 11–50%). The median AGREE overall rating was 5 (Q1–Q3: 4–6), and most were recommended for use (75%; 30/40). Twenty-nine NGs (43.3%; 29/67) scored ≥60% in three or more domains, including “rigor of development” domain. The methodological quality of NGs did not improve over time. Conclusion The methodological quality of NGs varies widely, but there is general need for improvement in most AGREE domains. NG developers could incorporate available tools to ensure the development of high-quality NGs.

ObjectiveTo determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature to 19 January 2021, and six additional Chinese databases to 20 January 2021.Study selectionRandomized trials in which people at risk of covid-19 were randomized to drug prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.ResultsThe first iteration of this living network meta-analysis includes nine randomized trials – six addressing hydroxychloroquine (6,059 participants), one addressing ivermectin combined with iota-carrageenan (234 participants) and two addressing ivermectin alone (540 participants), all compared to standard care or placebo. Hydroxychloroquine has no important effect on admission to hospital (risk difference (RD) 1 fewer per 1,000, 95% credible interval (CrI) 3 fewer to 4 more, high certainty) or mortality (RD 1 fewer per 1,000, 95% CrI 2 fewer to 3 more, high certainty). Hydroxychloroquine probably has no important effect on laboratory-confirmed infection (RD 2 more per 1,000, 95% CrI 18 fewer to 28 more, moderate certainty), probably increases adverse effects leading to drug discontinuation (RD 19 more per 1,000, 95% CrI 1 fewer to 70 more, moderate certainty) and may have no important effect on suspected, probable or laboratory-confirmed infection (RD 15 fewer per 1,000, 95% CrI 64 fewer to 41 more, low certainty). Due to serious risk of bias and very serious imprecision – and thus very low certainty evidence, the effects of ivermectin combined with iota-carrageenan on laboratory-confirmed infection (RD 52 fewer per 1,000, 95% CrI 58 fewer to 37 fewer), and ivermectin alone on laboratory-confirmed infection (RD 50 fewer per 1,000, 95% CrI 59 fewer to 16 fewer) and suspected, probable or laboratory-confirmed infection (RD 159 fewer per 1,000, 95% CrI 165 fewer to 144 fewer) remain uncertain.ConclusionHydroxychloroquine prophylaxis does not have an important effect on hospital admission and mortality, probably increases adverse effects, and probably does not have an important effect on laboratory-confirmed SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, we are highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection.Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.FundingThis study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Background A large body of evidence suggests that self-management interventions (SMIs) may improve outcomes in chronic obstructive pulmonary disease (COPD). However, accurate comparisons of the relative effectiveness of SMIs are challenging, partly due to heterogeneity of outcomes across trials and uncertainty about the importance of these outcomes for patients. We aimed to develop a core set of patient-relevant outcomes (COS) for SMIs trials to enhance comparability of interventions and ensure person-centred care. Methods We undertook an innovative approach consisting of four interlinked stages: i) Development of an initial catalogue of outcomes from previous EU-funded projects and/or published studies, ii) Scoping review of reviews on patients and caregivers’ perspectives to identify outcomes of interest, iii) Two-round Delphi online survey with patients and patient representatives to rate the importance of outcomes, and iv) Face-to-face consensus workshop with patients, patient representatives, health professionals and researchers to develop the COS. Results From an initial list of 79 potential outcomes, 16 were included in the COS plus one supplementary outcome relevant to all participants. These were related to patient and caregiver knowledge/competence, self-efficacy, patient activation, self-monitoring, adherence, smoking cessation, COPD symptoms, physical activity, sleep quality, caregiver quality of life, activities of daily living, coping with the disease, participation and decision-making, emergency room visits/admissions and cost effectiveness. Conclusion The development of the COPD COS for the evaluation of SMIs will increase consistency in the measurement and reporting of outcomes across trials. It will also contribute to more personalized health care and more informed health decisions in clinical practice as patients’ preferences regarding COPD outcomes are more systematically included.

IntroductionRapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic.Methods and analysisWe plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019. We will supplement our search with studies mapped by Cochrane Fertility and Gynaecology group, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), COVID-19 study repositories, reference lists and social media blogs. The search will be updated every week and not be restricted by language. We will include observational cohort (≥10 participants) and randomised studies reporting on prevalence of COVID-19 in pregnant and postpartum women, the rates of clinical manifestations and outcomes, risk factors in pregnant and postpartum women alone or in comparison with non-pregnant women with COVID-19 or pregnant women without COVID-19 and studies on tests and treatments for COVID-19. We will additionally include case reports and series with evidence on mother-to-child transmission of SARS-CoV-2 in utero, intrapartum or postpartum. We will appraise the quality of the included studies using appropriate tools to assess the risk of bias. At least two independent reviewers will undertake study selection, quality assessment and data extraction every 2 weeks. We will synthesise the findings using quantitative random effects meta-analysis and report OR or proportions with 95% CIs and prediction intervals. Case reports and series will be reported as qualitative narrative synthesis. Heterogeneity will be reported as I2 and τ2 statistics.Ethics and disseminationEthical approval is not required as this is a synthesis of primary data. Regular updates of the results will be published on a dedicated website (https://www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and disseminated through publications, social media and webinars.PROSPERO registration numberCRD42020178076.

Objective To propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 weeks) in the clinical, public health, and health systems fields. Study design and setting We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the GRADE Rapid Guidelines project group, and obtained feedback from the larger GRADE working group. Results A request for developing recommendations within two weeks is the usual trigger for an urgent response. While the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of four potential approaches: adopt existing recommendations; adapt existing recommendations; develop new recommendations using existing adequate systematic review; or develop new recommendations using expert panel input; and (8) consider an updating plan. Conclusion An urgent response for developing recommendations requires building a cohesive, skilled and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise, adapting to shifting needs, complying with the principles of transparency and properly managing conflicts of interest., Highlights • The proposed approach for developing trustworthy recommendations as part of urgent responses (1-2 weeks) builds on the general principles of trustworthy guideline development; • The approach proposes the following steps: (1) assess the level of urgency; (2) clarify and focus the scope of question(s); (3) prioritize and collect the information needed; (4) assess the adequacy of identified information; and then (5) develop recommendations; • Developing recommendations can consist of a) adopting existing recommendations; (b) adapting existing recommendations; c) developing new recommendations using existing systematic reviews; or d) developing new recommendations using identified information and panel input.

Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty). Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty), mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19. Janus kinase inhibitors appear to have promising benefits, but certainty is low. Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits. Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is publicly available in the supplementary material. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Properly conducted controlled clinical trials (CCTs) provide the highest level of evidence for optimising decision-making in healthcare. Electronic search strategies do not exhaustively retrieve them, because of issues related to indexing, exclusion of journals in languages other than English, among others. A handsearch approach is therefore warranted. We aimed to identify all CCTs published in Ophthalmology journals in Spain, to describe their main features, and to submit them to the Cochrane Register of CCTs (CENTRAL).After identifying all Spanish Ophthalmology Journals, we conducted a systematic handsearch following Cochrane guidelines. When appropriate, results were compared against electronic searches. A descriptive analysis was completed, including risk of bias assessment.We identified 18 eligible journals; 10 074 original articles, editorials, letters to the editor, abstracts and conference proceedings were assessed via handsearching for inclusion. Of these, 136 were subject to title and abstract screening, after which 102 were classified as CCTs. We identified three articles via electronic searches that had not been detected via handsearch, for a total of 105 CCTs. Among these, the most investigated pathologies were cataracts (32/105; 30.5%) and glaucoma (23/105 21.9%). Regarding risk of bias, 104/105 (99.0%) were deemed as "high risk of bias", mainly due to flaws in sequence generation and allocation concealment. 15/105 (14.3%) mentioned conflicts of interest, half of which had something to declare. No CCT reported adherence to CONSORT.Spanish Ophthalmology journals publish a low number of CCTs, with limited methodological quality. Handsearching was more sensitive than the electronic searching. Abbreviations CCT: Controlled clinical trial.

Objective The Guidelines International Network (G-I-N) Updating Guidelines Working Group launched an initiative to develop a glossary (the Updating Glossary) with domains, terms, definitions, and synonyms related to updating of clinical guidelines (CGs). Study Design and Setting The steering committee developed an initial list of domains, terms, definitions, and synonyms through brainstorming and discussion. The panel members participated in three rounds of feedback to discuss, refine, and clarify the proposed terms, definitions, and synonyms. Finally, the panel members were surveyed to assess their level of agreement regarding the glossary. Results Eighteen terms were identified and defined: (1) continuous updating, (2) decision to update, (3) fixed updating, (4) full updating, (5) impact of the new evidence, (6) partial updating, (7) prioritization process, (8) reporting process, (9) signal for an update, (10) surveillance process, (11) time of validity, (12) timeframe, (13) tools and resources, (14) up to date, (15) update cycle, (16) update unit, (17) updated version, and (18) updating strategy. Consensus was reached for all terms, definitions, and synonyms (median agreement scores ≥ 6); except for one term. Conclusions The G-I-N Updating Guidelines Working Group assembled the Updating Glossary to facilitate and improve the knowledge exchange among CGs developers, researchers, and users.

Outcome measurement in outpatient and day-care mental health facilities for children and adolescents in Spain remains limited, in part due to a lack of validated scales. To address this issue, we translated HoNOSCA (glossary, score sheet, self-rated questionnaire, and parent/legal guardian questionnaire) into Spanish and Catalan using a reverse translation approach. We ascertained the validity and psychometric quality of the HoNOSCA in Spanish by assessing correlation with the Children's Global Assessment Scale (C-GAS). We recruited 64 participants 7-17 years of age in five day-care Psychiatry hospitals in Catalonia (Spain). Two evaluators administered both instruments twice, two weeks apart. Patients and parents/legal guardians completed the corresponding HoNOSCA versions. We calculated Cronbach's alpha for assessing internal consistency, intra-class correlation coefficients (ICC) for inter-rater and test-retest reliability, and Pearson's correlation coefficients for validity. We found that all HoNOSCA versions in Spanish presented satisfactory internal consistency, inter-rater and test-retest reliability. Concurrent validity for HoNOSCA-Glossary was also acceptable, with Pearson's coefficients of -0.543 and -0.519 for evaluators in the first administration, and of -0.675 and -0.685 in the second administration. HoNOSCA was also successfully translated into Catalan; acceptability was determined using cognitive interviews.

Background To date there is no consensus about the optimal strategy for keeping clinical guidelines (CGs) up-to-date. The aims of this study were (1) to develop a continuous surveillance and updating strategy for CGs and (2) to test the strategy in a specific CG. Methods The main steps were as follows: (1) recruiting members for the CG Updating Working Group, (2) mapping the CG, (3) identifying new evidence from the CG Updating Working Group, (4) designing and running restricted literature searches, (5) reviewing drugs and medical devices alerts, (6) screening and assessing the new evidence, (7) reviewing and, if necessary, modifying clinical questions and recommendations, and (8) updating the CG document. Results The Pregnancy CG Updating Working Group consisted of 29 members, including clinicians, patients and caregivers, and clinical guideline methodology experts. We selected 69 clinical questions (123 recommendations) from the “Assistance during pregnancy” section. For the first update cycle (32-month duration), 9710 references were identified. Of these, 318 were pertinent, 289 were relevant, and 55 were classified as potential key references. For the second and third update cycles (6-month duration each), 2160 and 2010 references were retrieved, respectively. The continuous surveillance and updating strategy has not yet been completely implemented. Conclusions Further resources are needed in updating the CG field, both for implementing updating strategies and for developing methodological research.

Objectives The aim of the study was to identify and describe strategies to prioritize the updating of systematic reviews (SRs), health technology assessments (HTAs), or clinical guidelines (CGs). Study Design and Setting We conducted an SR of studies describing one or more methods to prioritize SRs, HTAs, or CGs for updating. We searched MEDLINE (PubMed, from 1966 to August 2016) and The Cochrane Methodology Register (The Cochrane Library, Issue 8 2016). We hand searched abstract books, reviewed reference lists, and contacted experts. Two reviewers independently screened the references and extracted data. Results We included 14 studies. Six studies were classified as descriptive (6 of 14, 42.9%) and eight as implementation studies (8 of 14, 57.1%). Six studies reported an updating strategy (6 of 14, 42.9%), six a prioritization process (6 of 14, 42.9%), and two a prioritization criterion (2 of 14, 14.2%). Eight studies focused on SRs (8 of 14, 57.1%), six studies focused on CGs (6 of 14, 42.9%), and none were about HTAs. We identified 76 prioritization criteria that can be applied when prioritizing documents for updating. The most frequently cited criteria were as follows: available evidence (19 of 76, 25.0%), clinical relevance (10 of 76; 13.2%), and users' interest (10 of 76; 13.2%). Conclusion There is wide variability and suboptimal reporting of the methods used to develop and implement processes to prioritize updating of SRs, HTAs, and CGs.

Objective We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. Study Design and Setting We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. Results We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1–13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). Conclusion About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

Rationale, aims, and objectivesSeveral studies have found that about half of research results from clinical trials are never published. Until now, there has been little information on the views that funding agencies of biomedical research in Europe have regarding this issue and its possible solutions. MethodsAn electronic survey was conducted among funding agencies from 34 European countries. Participants were asked about their opinions, policies, and potential solutions regarding dissemination bias. On the basis of the results of this survey and the input of the OPEN Consortium and of representatives of stakeholder groups in the knowledge generation process, we formulated recommendations for funding agencies to reduce dissemination bias. ResultsWe received responses from 64 funding agencies of biomedical medicine from most European countries, out of 245 that were contacted (26%). Of these, 56 funded research at the national and/or international level and were therefore eligible to participate. Policies encouraging publication increased over time: 33 (58.9%) of agencies enforced them in 2005 compared to 38 (67.6%) in 2012. However, only 13 (23.2%) had knowledge of the publications related to research funded in 2005, 23 (41.1%) were able to provide only an estimate, and 20 (35.7%) did not know at all. Regarding recommendations to control dissemination bias, we propose that funding agencies request the dissemination of research results irrespective of the direction of findings. We also call for measures that allow evaluating funded projects past the contractual period and until dissemination of results. Funding agencies should create publicly accessible databases with information on funded projects and dissemination efforts. ConclusionDespite having policies to encourage publication of results, most funding agencies fail to implement such measures or to ensure compliance. We propose recommendations that could be incorporated in the blueprint of calls for proposals and contracts agreed upon by funding agencies and grant recipients.

Background Vitamin D has been widely promoted for bone health through supplementation and fortification of the general population. However, there is growing evidence that does not support these strategies. Our aim is to review the quality and recommendations on vitamin D nutritional and clinical practice guidelines and explore predictive factors for their direction and strength. Methods We searched Medline, TRIP, G-I-N and guidelines.gov databases for guidelines from January 2010 to January 2018. We performed a descriptive analysis, a quality appraisal using AGREE II scores (Appraisal of Guidelines Research and Evaluation) and a bivariate analysis evaluating the association between direction and strength of recommendations, three AGREE II domains’ scores (Rigor of development, Applicability and Editorial Independence) and pre-specified characteristics. Results We included 24 guidelines in our review. Nine recommended supplementation, eight suggested its use, and seven did not recommend it. The mean score for “Rigor of development” domain was 40.1%. For the “Applicability” domain 34.5% and 39.6% for “Editorial independence” domain. The majority of guidelines did not reach and overall of 60% on these independent scores to be considered high quality. Guidelines with higher scores in these domains were less likely to recommend or suggest vitamin D supplementation (64% recommending against vs 29% suggesting for, and 27% recommending for; p=0.002, 52% vs 26% and 25%; p=0.003, 61% vs 35% and 24%; p=0.001, respectively). Guidelines with potential conflicts of interest were more likely to recommend or suggest vitamin D supplementation (likelihood ratio: p=0.018). Conclusions Policymakers, clinicians and patients should be aware that lower quality guidelines, and those reporting conflicts of interest are more likely to promote vitamin D supplementation. Guideline organizations should improve the quality of their recommendations’ development and the management of conflicts of interest. Users and editors should be aware of these findings when using and appraising guidelines.

IntroductionPersonal recovery has been defined as ‘a profound personal and unique process for the individual to change their attitudes, values, feelings, goals, abilities and roles in order to achieve a satisfactory, hopeful and productive way of life, with the possible limitations of the illness’. However, research on personal recovery has focused almost exclusively on adults. This project aims to systematically review the available literature on definitions of personal recovery among children and adolescents with mental health conditions and to undertake a narrative synthesis to develop a conceptual framework of recovery.Methods and analysisSystematic review and narrative synthesis consisting (1) searching scientific literature databases, (2) handsearching, (3) citation tracking, (4) grey literature searching, (5) web-based searching and expert consultation. We will include qualitative and quantitative studies or systematic reviews providing a definition, theoretical or conceptual framework, domains or dimensions of personal recovery among eligible participants. The study will follow standard systematic review methodology for study selection and data extraction. We will assess quality of the evidence using tools appropriate for each study design. We will develop a new conceptual framework using a modified narrative synthesis approach, as follows: (1) describing eligible studies and conducting a preliminary synthesis, (2) determining relationships within and between studies and (3) determining the robustness of the synthesis.Ethics and disseminationWe obtained a waiver of approval from our local Research Ethics Committee. Results will be disseminated via publications in international peer-reviewed journals and conference proceedings.This study will result in a theoretical framework that is based on an exhaustive review of the literature and the input of experts in the field of recovery. We expect that this framework will foster a better understanding of the stages and processes of recovery in children and adolescents with mental health conditions.PROSPERO registration numberCRD42018064087.

Background: The living systematic review (LSR) is an emerging approach for improved evidence synthesis that uses continual updating to include relevant new evidence as soon as it is published. The objectives of this study are to: 1) assess the methods of conduct and reporting of living systematic reviews using a living study approach; and 2) describe the life cycle of living systematic reviews, i.e., describe the changes over time to their methods and findings. Methods: For objective 1, we will begin by conducting a cross-sectional survey and then update its findings every 6 months by including newly published LSRs. For objective 2, we will conduct a prospective longitudinal follow-up of the cohort of included LSRs. To identify LSRs, we will continually search the following electronic databases: Medline, EMBASE and the Cochrane library. We will also contact groups conducting LSRs to identify eligible studies that we might have missed. We will follow the standard systematic review methodology for study selection and data abstraction. For each LSR update, we will abstract information on the following: 1) general characteristics, 2) systematic review methodology, 3) living approach methodology, 4) results, and 5) editorial and publication processes. We will update the findings of both the surveys and the longitudinal follow-up of included LSRs every 6 months. In addition, we will identify articles addressing LSR methods to be included in an ‘LSR methods repository’. Conclusion: The proposed living methodological survey will allow us to monitor how the methods of conduct, and reporting as well as the findings of LSRs change over time. Ultimately this should help with ensuring the quality and transparency of LSRs.

Background: There is still lack of consensus on the benefit-harm balance of breast cancer screening. In this scenario, women's values and preferences are crucial for developing health-related recommendations. In the context of the European Commission Initiative on Breast Cancer, we conducted a systematic review to inform the European Breast Guidelines. Methods: We searched Medline and included primary studies assessing women's values and preferences regarding breast cancer screening and diagnosis decision making. We used a thematic approach to synthesise relevant data. The quality of evidence was determined with GRADE, including GRADE CERQual for qualitative research. Results: We included 22 individual studies. Women were willing to accept the psychological and physical burden of breast cancer screening and a significant risk of overdiagnosis and false-positive mammography findings, in return for the benefit of earlier diagnosis. The anxiety engendered by the delay in getting results of diagnostic tests was highlighted as a significant burden, emphasising the need for rapid and efficient screening services, and clear and efficient communication. The confidence in the findings was low to moderate for screening and moderate for diagnosis, predominantly because of methodological limitations, lack of adequate understanding of the outcomes by participants, and indirectness. Conclusions: Women value more the possibility of an earlier diagnosis over the risks of a false-positive result or overdiagnosis. Concerns remain that women may not understand the concept of overdiagnosis. Women highly value time efficient screening processes and rapid result delivery and will accept some discomfort for the peace of mind screening may provide.

Background Infantile haemangiomas (IH) are soft swellings of the skin that occur in 3-10% of infants. When haemangiomas occur in high-risk areas or when complications develop, active intervention is necessary. Objective To update a Cochrane Review assessing the interventions for the management of IH in children. Methods We searched for randomized controlled trials in CENTRAL, MEDLINE, Embase, LILACS, AMED, PsycINFO, CINAHL and six trials registers up to February 2017. We included 28 trials (1728 participants) assessing 12 interventions. Results We downgraded evidence from high to moderate/low for issues related to risk of bias and imprecision. Oral propranolol (3 mg kg-1 daily) probably improves clinician-assessed clearance vs placebo [risk ratio (RR) 16·61, 95% confidence interval (CI) 4·22-65·34; moderate quality of evidence (QoE)]; we found no evidence of a difference in terms of serious adverse events (RR 1·05, 95% CI 0·33-3·39; low QoE). We found the chance of reduction of redness may be improved with topical timolol maleate (0·5% gel applied twice daily) when compared with placebo (RR 8·11, 95% CI 1·09-60·09; low QoE). We found no instances of bradycardia or hypotension for this comparison. Conclusions Our key results indicate that oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harm.

Objective To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. Design Living systematic review and network meta-analysis. Data sources World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. Study selection Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. Methods Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Results The first iteration of this living network meta-analysis includes nine randomised trials—six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. Conclusions Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. Systematic review registration This review was not registered. The protocol established a priori is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.