Effectiveness and Safety of Non-Invasive Neuromodulation for Vision Restoration: A Systematic Review and Meta-Analysis.

We carried out a systematic review and meta-analysis to determine the effectiveness and safety of non-invasive electrical stimulation (NES) for vision restoration. We systematically searched for randomised controlled trials (RCTs) comparing NES with sham stimulation, for vision restoration between 2000 and 2022 in CENTRAL, MEDLINE, EMBASE, and LILACS. The main outcomes were as follows: visual acuity (VA); detection accuracy; foveal threshold; mean sensitivity as the parameter for the visual field; reading performance; contrast sensitivity (CS); electroencephalogram; quality of life (QoL), and safety. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias using the Cochrane risk of bias 2.0 tool. The certainty in the evidence was determined using the GRADE framework. Protocol registration: CRD42022329342. Thirteen RCTs involving 441 patients with vision impairment indicate that NES may improve VA in the immediate post-intervention period (mean difference [MD] = -0.02 logMAR, 95% confidence intervals [CI] -0.08 to 0.04; low certainty), and probably increases QoL and detection accuracy (MD = 0.08, 95% CI -0.25 to 0.42 and standardised MD [SMD] = 0.09, 95% CI -0.58 to 0.77, respectively; both moderate certainty). NES likely results in little or no difference in mean sensitivity (SMD = -0.03, 95% CI -0.53 to 0.48). Compared with sham stimulation, NES increases the risk of minor adverse effects (risk ratio = 1.24, 95% CI 0.99 to 1.54; moderate certainty). The effect of NES on CS, reading performance, and electroencephalogram was uncertain. Our study suggests that although NES may slightly improve VA, detection accuracy, and QoL, the clinical relevance of these findings remains uncertain. Future research should focus on improving the available evidence's precision and consistency.

Low awareness of the transitivity assumption in complex networks of interventions: a systematic survey from 721 network meta-analyses.

BACKGROUND: The transitivity assumption is the cornerstone of network meta-analysis (NMA). Violating transitivity compromises the credibility of the indirect estimates and, by extent, the estimated treatment effects of the comparisons in the network. The present study offers comprehensive empirical evidence on the completeness of reporting and evaluating transitivity in systematic reviews with multiple interventions. METHODS: We screened the datasets of two previous empirical studies, resulting in 361 systematic reviews with NMA published between January 2011 and April 2015. We updated our evidence base with an additional 360 systematic reviews with NMA published between 2016 and 2021, employing a pragmatic approach. We devised assessment criteria for reporting and evaluating transitivity using relevant methodological literature and compared their reporting frequency before and after the PRISMA-NMA statement. RESULTS: Systematic reviews published after PRISMA-NMA were more likely to provide a protocol (odds ratio (OR): 3.94, 95% CI: 2.79-5.64), pre-plan the transitivity evaluation (OR: 3.01, 95% CI: 1.54-6.23), and report the evaluation and results (OR: 2.10, 95% CI: 1.55-2.86) than those before PRISMA-NMA. However, systematic reviews after PRISMA-NMA were less likely to define transitivity (OR: 0.57, 95% CI: 0.42-0.79) and discuss the implications of transitivity (OR: 0.48, 95% CI: 0.27-0.85) than those published before PRISMA-NMA. Most systematic reviews evaluated transitivity statistically than conceptually (40% versus 12% before PRISMA-NMA, and 54% versus 11% after PRISMA-NMA), with consistency evaluation being the most preferred (34% before versus 47% after PRISMA-NMA). One in five reviews inferred the plausibility of the transitivity (22% before versus 18% after PRISMA-NMA), followed by 11% of reviews that found it difficult to judge transitivity due to insufficient data. In justifying their conclusions, reviews considered mostly the comparability of the trials (24% before versus 30% after PRISMA-NMA), followed by the consistency evaluation (23% before versus 16% after PRISMA-NMA). CONCLUSIONS: Overall, there has been a slight improvement in reporting and evaluating transitivity since releasing PRISMA-NMA, particularly in items related to the systematic review report. Nevertheless, there has been limited attention to pre-planning the transitivity evaluation and low awareness of the conceptual evaluation methods that align with the nature of the assumption.

Patients' values and preferences for health states in allergic rhinitis-An artificial intelligence supported systematic review.

BACKGROUND: Allergic rhinitis (AR) impacts patients' physical and emotional well-being. Assessing patients' values and preferences (V&P) related to AR is an essential part of patient-centered care and of the guideline development process. We aimed to systematically summarize the information about patients' V&P on AR and its symptoms and impact on daily life. METHODS: We conducted systematic review in a MEDLINE, Embase, PsychInfo, and CINAHL databases. We included studies which quantitatively assessed patients' V&P for specific outcomes in AR by assessing utilities, applying discrete choice approaches, or rating and ranking outcomes. We grouped outcomes as AR symptoms, functional status, and care-related patient experience. Study selection and data extraction were supported by the Laser AI tool. We rated the certainty of evidence (CoE) using the GRADE approach. RESULTS: Thirty-six studies (41 records) were included: nine utility studies, seven direct-choice studies and 21 studies of rating or ranking outcomes. Utilities were lower with increased AR severity and with the concomitant presence of asthma, but not with whether AR was seasonal or perennial (CoE = low-high). Patients rated AR symptom-related outcomes as more important than those related to care-related patient experience and functional status (CoE = very low-moderate). Nasal symptoms (mainly nasal congestion) followed by breathing disorders, general and ocular symptoms were rated as the symptoms with the highest impact. CONCLUSIONS: This systematic review provides a comprehensive overview of V&P of patients with AR. Patients generally considered nasal symptoms as the most important. Future studies with standardized methods are needed to provide more information on V&P in AR.

Clinical practice guideline on the use of single-operator cholangioscopy in the diagnosis of indeterminate biliary stricture and the treatment of difficult biliary stones.

BACKGROUND AND AIMS: Single-operator cholangioscopy (SOC) offer a diagnostic and therapeutic alternative with an improved optical resolution over conventional techniques; however, there are no standardized clinical practice guidelines for this technology. This evidence-based guideline from the Colombian Association of Digestive Endoscopy (ACED) intends to support patients, clinicians, and others in decisions about using in adults the SOC compared to endoscopic retrograde cholangiopancreatography (ERCP), to diagnose indeterminate biliary stricture and to manage difficult biliary stones. METHODS: ACED created a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. Universidad de los Andes and the Colombia Grading of Recommendations Assessment, Development and Evaluation (GRADE) Network supported the guideline-development process, updating and performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The GRADE approach was used, including GRADE Evidence-to-Decision frameworks. RESULTS: The panel agreed on one recommendation for adult patients with indeterminate biliary strictures and one for adult patients with difficult biliary stones when comparing SOC versus ERCP. CONCLUSION: For adult patients with indeterminate biliary strictures, the panel made a conditional recommendation for SOC with stricture pattern characterization over ERCP with brushing and/or biopsy for sensitivity, specificity, and procedure success rate outcomes. For the adult patients with difficult biliary stones the panel made conditional recommendation for SOC over ERCP with large-balloon dilation of papilla. Additional research is required on economic estimations of SOC and knowledge translation evaluations to implement SOC intervention in local contexts.

Topical treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD prescription topical treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s). RESULTS: The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. CONCLUSIONS: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.

Community-Based Knowledge Translation Strategies for Maternal, Neonatal, and Perinatal Outcomes: A Systematic Review of Quantitative and Qualitative Data.

Objective: To identify and assess the effect of community-based Knowledge Translation Strategies (KTS) on maternal, neonatal, and perinatal outcomes. Methods: We conducted systematic searches in Medline, Embase, CENTRAL, CINAHL, PsycInfo, LILACS, Wholis, Web of Science, ERIC, Jstor, and Epistemonikos. We assessed the certainty of the evidence of the studies using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: We identified seven quantitative and seven qualitative studies. Quantitative findings suggest that there is a possible effect on reducing maternal mortality (RR 0.65; 95% CI, 0.48-0.87; moderate evidence certainty); neonatal mortality (RR 0.79; 95% CI 0.70-0.90; moderate evidence certainty); and perinatal mortality (RR 0.84; 95% CI 0.77-0.91; moderate evidence certainty) in women exposed to KTS compared to those who received conventional interventions or no intervention at all. Analysis of qualitative studies identified elements that allowed to generate benefit effects in improving maternal, neonatal, and perinatal outcomes. Conclusion: The KTS in maternal, neonatal, and perinatal outcomes might encourage the autonomy of communities despite that the certainty of evidence was moderate.

Improving grading of recommendations assessment, development, and evaluation evidence tables part 4: a three-arm noninferiority randomized trial demonstrates improved understanding of content in summary of findings tables with a new format.

OBJECTIVES: To evaluate alternative formats of summary of findings (SoF) tables for single comparison with multiple outcomes. STUDY DESIGN AND SETTING: We conducted a three-arm randomized controlled noninferiority trial (RCT) in the following systematic review (SR) users: researchers, clinical practice guideline developers, health care providers, policymakers, and knowledge transfer organizations to measure understanding, accessibility, satisfaction, and preference across the current grading of recommendations assessment, development, and evaluation (GRADE) SoF, an alternative GRADE SoF, or an adapted evidence-based practice center (EPC) program SoF table. RESULTS: One Hundred Seventy-Nine participants were randomized, and 129 participants completed the RCT (n = 47 current GRADE, n = 41 alternative GRADE, n = 41 adapted EPC). Understanding the certainty of evidence and treatment effect was comparable across groups. The adapted EPC SoF table was inferior for quantifying risk and RD compared to the alternatives (<35% correct vs. >85% correct). Participants reported increased satisfaction when SoF tables presented number needed to treat (NNT), anticipated absolute effect differences, and narrative syntheses for evidence that could not be meta-analyzed. Participants reported accessibility to information as significantly better in both GRADE SoF tables, when compared with the adapted EPC SoF table. Participants preferred the alternative GRADE SoF table format. CONCLUSION: The alternative GRADE SoF table is a promising format for SR users preferring a comprehensive presentation of SR results for single comparisons.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

Effectiveness and adherence to closed face shields in the prevention of COVID-19 transmission: a non-inferiority randomized controlled trial in a middle-income setting (COVPROSHIELD).

BACKGROUND: The use of respiratory devices can mitigate the spread of diseases such as COVID-19 in community settings. We aimed to determine the effectiveness of closed face shields with surgical face masks to prevent SARS-CoV-2 transmission in working adults during the COVID-19 pandemic in Bogotá, Colombia. METHODS: An open-label non-inferiority randomized controlled trial that randomly assigned participants to one of two groups: the intervention group was instructed to wear closed face shields with surgical face masks, and the active control group was instructed to wear only surgical face masks. The primary outcome was a positive reverse transcription polymerase chain reaction test, IgG/IgM antibody test for SARS-CoV-2 detection, or both during and at the end of the follow-up period of 21 days. The non-inferiority limit was established at - 5%. RESULTS: A total of 316 participants were randomized, 160 participants were assigned to the intervention group and 156 to the active control group. In total, 141 (88.1%) participants in the intervention group and 142 (91.0%) in the active control group completed the follow-up. PRIMARY OUTCOME: a positive SARS-CoV-2 test result was identified in one (0.71%) participant in the intervention group and three (2.1%) in the active control group. In the intention-to-treat analysis, the absolute risk difference was - 1.40% (95% CI [- 4.14%, 1.33%]), and in the per-protocol analysis, the risk difference was - 1.40% (95% CI [- 4.20, 1.40]), indicating non-inferiority of the closed face shield plus face mask (did not cross the non-inferiority limit). CONCLUSIONS: The use of closed face shields and surgical face masks was non-inferior to the surgical face mask alone in the prevention of SARS-CoV-2 infection in highly exposed groups. Settings with highly active viral transmission and conditions such as poor ventilation, crowding, and high mobility due to occupation may benefit from the combined use of masks and closed face shields to mitigate SARS-CoV-2 transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT04647305 . Registered on November 30, 2020.

Evidence to decision frameworks enabled structured and explicit development of healthcare recommendations.

OBJECTIVE: The aim of this study is to identify and describe the processes suggested for the formulation of healthcare recommendations in healthcare guidelines available in guidance documents. METHODS: We searched international databases in May 2020 to retrieve guidance documents published by organizations dedicated to guideline development. Pairs of researchers independently selected and extracted data about the characteristics of the guidance document, including explicit or implicit recommendation-related criteria and processes considered, as well as the use of evidence to decision (EtD) frameworks. RESULTS: We included 68 guidance documents. Most organizations reported a system for grading the strength of recommendations (88%), half of them being the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Two out of three guidance documents (66%) proposed the use of a framework to guide the EtD process. The GRADE-EtD framework was the most often reported framework (19 organizations, 42%), whereas 20 organizations (44%) proposed their own multicriteria frameworks. Using any EtD framework was related with a more comprehensive set of recommendation-related criteria compared to no framework, especially for criteria like values, equity, and acceptability. CONCLUSION: Although limited, the use of EtD frameworks was associated with the inclusion of relevant recommendation criteria. Among the EtD structured frameworks, the GRADE-EtD framework offers the most comprehensive perspective for evidence-informed decision-making processes.

Predictors of 1-year mortality after adult lung transplantation: Systematic review and meta-analyses.

BACKGROUND: Prognostic factors in lung transplantation are those variables that are associated with transplant outcomes. Knowledge of donor and recipient prognostic variables can aid in the optimal allocation of donor lungs to transplant recipients and can also inform post-operative discussions with patients about prognosis. Current research findings related to prognostic factors in lung transplantation are inconsistent and the relative importance of various factors is unclear. This review aims to provide the best possible estimates of the association between putative prognostic variables and 1-year all-cause mortality in adult lung transplant recipients. METHODS: We searched 5 bibliographic databases for studies assessing the associations between putative predictors (related to lung donors, recipients, or the transplant procedure) and 1-year recipient mortality. We pooled data across studies when justified and utilized GRADE methodology to assess the certainty in the evidence. RESULTS: From 72 eligible studies (2002-2020), there were 34 recipient variables, 4 donor variables, 10 procedural variables, and 7 post-transplant complication variables that were amenable to a meta-analysis. With a high degree of certainty in the evidence only post-transplant need for extra-corporeal membrane oxygenation (ECMO) (HR 1.91, 95% CI 1.79-2.04) predicted 1-year mortality. No donor variables appeared to predict transplant outcome with high or even moderate certainty. CONCLUSION: Across the range of contemporary donors and recipients that clinicians accept for lung transplantation, this review, with high certainty, found 1 prognostic factor that predicted 1-year mortality, and 37 additional factors with a moderate degree of certainty. The lack of prognostic significance for some widely accepted factors (e.g., donor smoking, age) likely relates to existing limits in the range of these variables at the time of donor and recipient selection.

GRADE summary of findings tables enhanced understanding of values and preferences evidence.

OBJECTIVES: 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. STUDY DESIGN AND SETTING: 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). RESULTS: 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. CONCLUSION: 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.

Classic test and generalizability theories are both useful for cross-cultural adaptation of an allergic rhinitis health-related quality of life questionnaire.

BACKGROUND: An instrument to assess Allergic Rhinitis (AR) Health-Related Quality of Life (HRQL) in adult patients was developed in Spain. No validated instrument is currently cross-culturally adapted for use in daily practice to assess HRQL in AR patients in Colombia. PURPOSE: The aim of this study was to evaluate the measurement performance of an AR-HRQL specific questionnaire, ESPRINT-15 (Cuestionario ESPañol de Calidad de Vida en RINiTis), in Colombian adult patients with AR using the Classic Test Theory (CTT) and the Generalizability theory (G-theory) frameworks. METHODS: We conducted the cross-cultural adaptation in 2 stages. In stage 1, we evaluated comprehensibility, acceptability, and feasibility of ESPRINT-15 in healthy adults and adult patients with AR. In stage 2, we examined both reliability and validity of ESPRINT-15 scores using CTT and overall reliability applying the G-theory in adult patients with AR. RESULTS: For feasibility and acceptability, all items showed a higher than 95% level of understanding, and modifications in the original questionnaire were unnecessary. Reliability and validity using CTT showed a high internal consistency (Cronbach's alpha and Mc McDonald's omega = 0.95) and test-retest reliability (scores from 0.70 to 0.76). The overall reliability score using G-theory was 0.75, and G-coefficients scores associated with internal consistency and test-retest reliability measures were 0.96 and 0.61, respectively. Validity using exploratory factor analysis (EFA) identified 2 factors instead of the original ESPRINT-15 4 domains. However, confirmatory factor analysis (CFA) showed good fit regarding the original model. CONCLUSIONS: The proposed cross-cultural adaptation of ESPRINT-15 showed good reliability and validity measures. Additionally, it was easy to use and administer. ESPRINT-15 can be used clinically and for research in Colombian adults' patients with AR. CTT and the G-theory can be used in epidemiological studies to adapt AR-HRQL questionnaires cross-culturally in adult patients with AR.

Patient-important outcomes reported in randomized controlled trials of pharmacologic treatments for COVID-19: a protocol of a META-epidemiological study.

BACKGROUND: The coronavirus disease 19 (covid-19) pandemic has underscored the need to expedite clinical research, which may lead investigators to shift away from measuring patient-important outcomes (PIO), limiting research applicability. We aim to investigate if randomized controlled trials (RCTs) of covid-19 pharmacological therapies include PIOs. METHODS: We will perform a meta-epidemiological study of RCTs that included people at risk for, or with suspected, probable, or confirmed covid-19, examining any pharmacological treatment or blood product aimed at prophylaxis or treatment. We will obtain data from all RCTs identified in a living network metanalysis (NMA). The main data sources are the living WHO covid-19 database up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Two reviewers independently will review each citation, full-text article, and abstract data. To categorize the outcomes according to their importance to patients, we will adapt a previously defined hierarchy: a) mortality, b) quality of life/ functional status/symptoms, c) morbidity, and d) surrogate outcomes. Outcomes within the category a) and b) will be considered critically important to patients, and outcomes within the category c) will be regarded as important. We will use descriptive statistics to assess the proportion of studies that report each category of outcomes. We will perform univariable and multivariable analysis to explore associations between trial characteristics and the likelihood of reporting PIOs. DISCUSSION: The findings from this meta-epidemiological study will help health care professionals and researchers understand if the current covid-19 trials are effectively assessing and reporting the outcomes that are important to patients. If a deficiency in capturing PIOs is identified, this information may help inform the development of future RCTs in covid-19. SYSTEMATIC REVIEW REGISTRATIONS: Open Science Framework registration: osf.io/6xgjz .

Vitamin D recommendations in clinical guidelines: A systematic review, quality evaluation and analysis of potential predictors.

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 to 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 = .001 and 58.3 vs 37.5; P = .02). Guidance produced by government organisations 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 = .034). Editorial independence was an independent predictor for recommending or suggesting vitamin D supplementation (OR 1.09; CI95% 1.02 to 1.16; P = .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 organisations 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.

Clinical trials in COVID-19 management & prevention: A meta-epidemiological study examining methodological quality.

OBJECTIVE: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. STUDY DESIGN: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. RESULTS: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled <50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect. CONCLUSIONS: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs. REGISTRATION: CRD42020192095.

A modeling approach to derive baseline risk estimates for GRADE recommendations: Concepts, development, and results of its application to the American Society of Hematology 2019 guidelines on prevention of venous thromboembolism in surgical hospitalized patients.

OBJECTIVE: The goal of this study was to develop an approach that can be used where baseline risk estimates that are directly applicable to prioritized patient-important outcomes are not available from published studies. STUDY DESIGN: The McMaster University GRADE Centre and the ASH guideline panel for the prevention of VTE in surgical patients developed a modeling approach based on explicit assumptions about the distribution of symptoms, anatomical location, and severity of VTE events. RESULTS: We applied the approach to derive modeled estimates of baseline risk. These estimates were used to calculated absolute measures of anticipated effects that informed the discussion of the evidence and the formulation of 30 guideline recommendations. CONCLUSION: Our approach can assist guideline developers facing a lack of information about baseline risk estimates that directly apply to outcomes of interest. The use of modeled estimates increases transparency in the process and makes the baseline risk used by guideline experts explicit during their decision-making.

Using GRADE evidence to decision frameworks to choose from multiple interventions.

BACKGROUND AND OBJECTIVE: Guideline development groups or other health care decision makers frequently encounter situations that require a simultaneous comparison of multiple interventions. This sometimes becomes apparent either when they identify questions of interest, before they formulate recommendations, or it may surface only when recommendations have already been formulated based on pairwise comparisons. METHODS: Using examples from the World Health Organization, the European Commission, and a professional society, we developed a flexible approach to developing recommendations when a multiple-intervention comparison (MC) is needed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) frameworks. We iteratively refined this approach through user testing and then included a module in GRADE's official software GRADEpro to test the approach in two real and one theoretical guideline recommendations. RESULTS: We found the approach feasible and that all EtD criteria should be considered in an MC approach. We judged that guideline development groups and other decision makers will benefit from the availability of a network meta-analyses (NMA) of intervention effects to support decisions; however, NMA supports only one of many criteria, that is, the balance of health benefits and harms, and is therefore helpful, but not essential to the approach we propose. When similar but not identical comparators are used to address MC, challenges may arise with intransitivity and the relative rankings of interventions. CONCLUSION: We successfully applied the MC approach and software module in generating recommendations across different scenarios and identified challenges. The MC approach allows guideline groups and other decision makers to transparently and critically assess multiple options for a given health question. Application of the approach by others may lead to refinement and allow for better understanding of its impact in developing recommendations and making choices.

Assessing the process and outcome of the development of practice guidelines and recommendations: PANELVIEW instrument development.

BACKGROUND: Guideline recommendations may be affected by flaws in the process, inappropriate panel member selection or conduct, conflicts of interest and other factors. To our knowledge, no validated tool exists to evaluate guideline development from the perspective of those directly involved in the process. Our objective was to develop and validate a universal tool, the PANELVIEW instrument, to assess guideline processes, methods and outcomes from the perspective of the participating guideline panellists and group members. METHODS: We performed a systematic literature search and surveys of guideline groups (identified through contacting international organizations and convenience sampling of working panels) to inform item generation. Subsequent groups of guideline methodologists and panellists reviewed items for face validity and missing items. We used surveys, interviews and expert review for item reduction and phrasing. For reliability assessment and feedback, we tested the PANELVIEW tool in 8 international guideline groups. RESULTS: We surveyed 62 members from 13 guideline panels, contacted 19 organizations and reviewed 20 source documents to generate items. Fifty-three additional key informants provided feedback about phrasing of the items and response options. We reduced the number of items from 95 to 34 across domains that included administration, training, conflict of interest, group dynamics, chairing, evidence synthesis, formulating recommendations and publication. The tool takes about 10 minutes to complete and showed acceptable measurement properties. INTERPRETATION: The PANELVIEW instrument fills a gap by enabling guideline organizations to involve clinicians, patients and other participants in evaluating their guideline processes. The tool can inform quality improvement of existing or new guideline programs, focusing on insight into and transparency of the guideline development process, methods and outcomes.