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The goal of nonrestorative or non- and microinvasive caries treatment (fluoride- and nonfluoride-based interventions) is to manage the caries disease process at a lesion level and minimize the loss of sound tooth structure. The purpose of this systematic review and network meta-analysis was to summarize the available evidence on nonrestorative treatments for the outcomes of 1) arrest or reversal of noncavitated and cavitated carious lesions on primary and permanent teeth and 2) adverse events. We included parallel and split-mouth randomized controlled trials where patients were followed for any length of time. Studies were identified with MEDLINE and Embase via Ovid, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews. Pairs of reviewers independently conducted the selection of studies, data extraction, risk-of-bias assessments, and assessment of the certainty in the evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Data were synthesized with a random effects model and a frequentist approach. Forty-four trials (48 reports) were eligible, which included 7,378 participants and assessed the effect of 22 interventions in arresting or reversing noncavitated or cavitated carious lesions. Four network meta-analyses suggested that sealants + 5% sodium fluoride (NaF) varnish, resin infiltration + 5% NaF varnish, and 5,000-ppm F (1.1% NaF) toothpaste or gel were the most effective for arresting or reversing noncavitated occlusal, approximal, and noncavitated and cavitated root carious lesions on primary and/or permanent teeth, respectively (low- to moderate-certainty evidence). Study-level data indicated that 5% NaF varnish was the most effective for arresting or reversing noncavitated facial/lingual carious lesions (low certainty) and that 38% silver diamine fluoride solution applied biannually was the most effective for arresting advanced cavitated carious lesions on any coronal surface (moderate to high certainty). Preventing the onset of caries is the ultimate goal of a caries management plan. However, if the disease is present, there is a variety of effective interventions to treat carious lesions nonrestoratively. [ABSTRACT FROM AUTHOR]

Background: The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain., Objectives: To compare the effectiveness and safety of alternative empiric antibiotic regimens in HAP using a network meta-analysis., Data Sources: Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023., Study Eligibility Criteria: RCTs., Participants: Adults with clinical suspicion of HAP., Interventions: Any empiric antibiotic regimen vs. another, placebo, or no treatment., Assessment of Risk of Bias: Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials., Methods of Data Synthesis: Paired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects network meta-analyses for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach., Results: Thirty-nine RCTs proved eligible. Thirty RCTs involving 4807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs. antipseudomonal cephalosporins or antipseudomonal carbapenems vs. antipseudomonal cephalosporins. Eleven RCTs involving 2531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis., Conclusions: For empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure. Empiric methicillin-resistant Staphylococcus aureus coverage may not exert additional benefit in reducing mortality., Registration: PROSPERO (CRD 42022297224)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: To compare neonatal, obstetrical, and maternal outcomes associated with outpatient vs inpatient management of pregnancies with preterm prelabor rupture of membranes (PPROM)., Material and Methods: A search of MEDLINE, EMBASE, the Cochrane Database and Central Register from January 1, 1990 to July 31, 2023 identified randomized controlled trials (RCTs) and cohort studies comparing outpatient with inpatient management for pregnant persons diagnosed with PPROM before 37 weeks' gestation. No language restriction was applied. We applied a random effects model for meta-analysis. Trustworthiness was assessed using recently published guidance and Risk of bias using the RoB 2.0 tool for RCTs and ROBINS-I tool for cohort studies. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the certainty of evidence (COE). Outcomes of interest included perinatal mortality, neonatal morbidities, latency and gestational age at delivery, and maternal morbidities. RCTs and cohort studies were analyzed separately. This study was registered in the International Prospective Register of Systematic Reviewsr: CRD42022295275., Results: From 2825 records, two RCTs and 10 cohort studies involving 1876 patients were included in the review and meta-analysis. Outpatient management protocols varied but generally included brief initial hospitalization, strict eligibility criteria, and surveillance with laboratory and ultrasound investigations. Outpatient management showed lower rates of neonatal respiratory distress syndrome (cohort: RR 0.63 [0.52-0.77, very low COE]), longer latency to delivery (RCT: MD 7.43 days [1.14-13.72 days, moderate COE], cohort: MD 8.78 days [2.29-15.26 days, low COE]), higher gestational age at birth (cohort: MD 7.70 days [2.02-13.38 days, low COE]), lower rates of Apgar scores <7 at 5 min of life (cohort: RR 0.66 [0.50-0.89, very low COE]), and lower rates of histological chorioamnionitis (cohort: RR 0.74 [0.62-0.89, low COE]) without increased risks of adverse neonatal, obstetrical, or maternal outcomes., Conclusions: Meta-analysis of data from RCTs and cohort studies with very low-to-moderate certainty of evidence indicates that further high-quality research is needed to evaluate the safety and potential benefits of outpatient management for selected PPROM cases, given the moderate-to-high risk of bias in the included studies., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Importance: The optimal inhaled reliever therapy for asthma remains unclear., Objective: To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma., Data Sources: The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions., Study Selection: Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers)., Data Extraction and Synthesis: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence., Main Outcomes and Measures: Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events., Results: A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], -10.3% [95% CI, -11.8% to -8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, -4.7% [95% CI, -8.0% to -1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, -5.5% [95% CI, -8.4% to -2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, -0.6% [95% CI, -1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, -1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty)., Conclusions and Relevance: In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

COVID-19-related critical and acute illness are associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other healthcare professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness, acute illness, and those being discharged from the hospital, who do not have suspected or confirmed VTE. ASH formed a multidisciplinary panel, including three patient representatives, and applied a conflicts of interest management policy to minimize potential bias. The Michael G. DeGroote Cochrane Canada and MacGRADE Centres at McMaster University supported the guideline development process, including performing systematic evidence reviews (up to June 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess certainty of the evidence and make recommendations, which were subject to public comment. This is an executive summary of three updated recommendations that have been published which concludes the living phase of the guidelines. For critically ill patients with COVID-19, the panel issued conditional recommendations in favor of (a) prophylactic-intensity over therapeutic-intensity anticoagulation and (b) prophylactic-intensity over intermediate-intensity anticoagulation. For acutely ill patients with COVID-19, conditional recommendations were made in favor of (a) prophylactic-intensity over intermediate-intensity anticoagulation and (b) therapeutic-intensity over prophylactic-intensity anticoagulation. The panel also issued a conditional recommendation against the use of post-discharge extended pharmacologic thromboprophylaxis. These three conditional recommendations were made based on low or very low certainty in the evidence, underscoring the need for additional, high-quality randomized controlled trials in patients with COVID-19-related illness., (Copyright © 2024 American Society of Hematology.)

Objective: The PANELVIEW questionnaire identifies the strengths and weaknesses of the process and methods used for developing health guidelines from the guideline development group's perspective. To expand its use, PANELVIEW ideally should be available in different languages. We aimed to cross-culturally adapt PANELVIEW into Spanish and assess its acceptability, validity, and reliability., Study Design and Setting: To translate and culturally adapt PANELVIEW to Spanish, we followed ISPOR's Translation and Cultural Adaptation Good Practice Principles guidelines. The process consisted of 1) forward and back translation, 2) input from an expert panel, and 3) cognitive debriefing interviews. We assessed the content validity with experts in guideline development who rated instrument items for relevance to determine the item and scale content validity index (I-CVI; S-CVI). We tested the reliability with health guidelines panels from Spanish-speaking countries and measured internal consistency (Cronbach's alpha). We examined acceptability through the number of missing responses for each item., Results: The content comparison between the back-translation and the original version showed that most items (24/34) were conceptually equivalent but with grammatical differences. Through the cognitive interviews, we identified six items with wording issues, ten with clarity issues, and two with applicability issues. I-CVI ranged from 0.77 to 1.00, with two items needing revision. S-CVI was 0.92, showing excellent content validity. The PANELVIEW Spanish version demonstrated very good reliability (Cronbach's alpha coefficient of 0.96). Panel members responded to all items, showing good acceptability., Conclusion: The PANELVIEW Spanish version was conceptually equivalent to the original version and provided satisfactory evidence of acceptability, validity and reliability., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)-ADOLOPMENT methodology has been widely used to adopt, adapt, or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. The objective of this guidance is to refine the operationalization for applying GRADE-ADOLOPMENT., Methods: Through iterative discussions, online meetings, and email communications, the GRADE-ADOLOPMENT project group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE working group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people), and twice in September 2023 (approximately 60 and 90 people) for approval., Results: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by doing the following: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing evidence-to-decision (EtDs), when available or developing new EtDs, if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others., Conclusion: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over 6 years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources., Competing Interests: Declaration of competing interest The authors are members or contributors to the GRADE working group. Zachary Munn is supported by an NHMRC investigator grant APP 1195676. Alexander G. Mathioudakis was supported by the National Institute for Health and Care Research Manchester Biomedical Research Centre (NIHR Manchester BRC, NIHR203308) and by an NIHR Clinical Lectureship in Respiratory Medicine. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care., (Copyright © 2024. Published by Elsevier Inc.)

Multiple randomized controlled trials (RCTs) have examined first-line pharmacological agents such as anticholinergics and β3 agonists for the management of overactive bladder symptoms (OAB). Although earlier systematic reviews and (network) meta-analyses aimed to summarize the evidence, a substantial number of trials were not included, so a comprehensive and methodologically rigorous evaluation of the comparative effectiveness of all first-line pharmacological treatments is lacking. We aim to conduct a series of systematic reviews and network meta-analyses (NMAs) for a comprehensive assessment of the effectiveness and safety of first-line pharmacological treatments for OAB. Eligible studies will include RCTs comparing anticholinergics and β3 agonists to one another or to placebo in adults with OAB or detrusor overactivity. Pairs of reviewers with methodological training will independently evaluate candidate studies to determine eligibility and extract relevant data. We will incorporate patient-important outcomes, including urinary urgency episodes, urgency incontinence episodes, any type of incontinence episodes, urinary frequency, nocturia, and adverse events. We will conduct the NMAs using a frequentist framework and a graph theory model for each outcome. Analysis will follow rigorous methodologies, including handling of missing data and assessment of the risk of bias. We will conduct sensitivity and subgroup analyses and will apply the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate evidence certainty. Our approach aims to address the knowledge gap in the treatment of OAB by synthesizing evidence from RCTs worldwide. We will employ robust statistical methods, including frequentist NMA, to general clinically relevant and patient-important insights. Sensitivity and subgroup analyses will enhance the robustness and generalizability of our findings. Our reviews strive to inform evidence-based decisions in the management of OAB, to ultimate improve patient outcomes. Our study results may guide health policy decisions, such as reimbursement policies, and future studies in functional urology. The protocol for the review series is registered on PROSPERO as CRD42023266915., (© 2024 The Author(s).)

Background: Gender dysphoria (GD) refers to psychological distress associated with the incongruence between one's sex and one's gender. In response to GD, birth-registered females may choose to undergo mastectomy. In this systematic review, we summarize and assess the certainty of the evidence on the effects of mastectomy., Methods: We searched MEDLINE, Embase, PsycINFO, Social Sciences Abstracts, LGBTQ+ Source, and Sociological Abstracts through June 20, 2023. We included studies comparing mastectomy to no mastectomy in birth-registered females under 26 years of age with GD. Outcomes of interest included psychological and psychiatric outcomes, and physical complications. Pairs of reviewers independently screened articles, abstracted data, and assessed risk of bias of the included studies. We performed meta-analysis and assessed the certainty of the evidence using the GRADE approach., Results: We included 39 studies. Observational studies (n=2) comparing mastectomy to chest binding provided very low certainty evidence for the outcome of GD. One observational study comparing mastectomy to no mastectomy provided very low certainty evidence for the outcomes global functioning and suicide attempts, and low certainty evidence for the outcome non-suicidal self-injury (aOR 0.47 [95% CI 0.22 to 0.97]). Before-after (n=2) studies provided very low certainty evidence for all outcomes. Evidence from case series (n=34) studies ranged from high to very low certainty., Conclusion: Case series studies demonstrated high certainty evidence for the outcomes of death, necrosis, and excessive scarring; however, these are limited in methodological quality. In comparative and before-after studies the evidence ranged from low to very low certainty., Competing Interests: Disclosure Statement: Management of conflicts of interest: We conducted this SR is part of a research agreement between the Society for Evidence-based Gender Medicine (SEGM), the sponsor, and McMaster University. None of the researchers conducting this SR and meta-analysis received direct financial compensation from the sponsor to conduct this work. The SR and meta-analysis research question was designed through a collaboration between SEGM representatives, independent researchers, and the methods team based at McMaster University. Independent researchers who do not have any financial or intellectual conflicts of interest or disclosures, and the methodology team based at McMaster University (the group of authors) conducted the rest of the SR and meta-analysis processes (i.e., search, data extraction, data analyses, manuscript writing, approval of final draft of manuscript). The methods team was solely responsible for the synthesis and interpretation of results, and for drawing conclusions. To minimize bias, a methodologist who was not involved in the data collection, synthesis, and interpretation (GG) ensured that results interpretation was consistent with the findings. This manuscript was drafted by the methods team and approved by all authors, and the sponsor did not have any say in its content. Conflicts of interest: Dr. Romina Brignardello and Anna Miroshnychenko provided methodological expertise for the SEGM initiative to summarize and appraise the quality of publications related to gender medicine for the SEGM online platform and received financial compensation from SEGM. Dr. Romina Brignardello-Petersen presented preliminary results at the conference titled International Perspectives of Evidence Based Treatment for Gender Dysphoric Youth (New York, 2023 ). Dr. Yetiani M Roldan, Sara Ibrahim, Dr. Steven Montante and Rachel Couban have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.)

Workshops or training sessions on medical writing and publishing exist worldwide. We aimed to evaluate published articles about such workshops and examine both the content and teaching strategies employed. We searched ISI Web of Science, Ovid EMBASE, ERIC, Ovid Medline, and the grey literature. We considered no language, geographical location, or time period limitations. We included randomized controlled trials, before-after studies, surveys, cohort studies, and program evaluation and development studies. We descriptively reported the results. Out of 222 articles that underwent a full-text review, 30 were deemed eligible. The educational sessions were sporadic, with researchers often developing their own content and methods. Fifteen articles reported teaching the standard structure of medical articles, ten articles reported on teaching optimal English language use for writing articles, nine articles discussed publication ethics issues, and three articles discussed publication strategies to enhance the chance of publication. Most reports lacked in-depth descriptions of the content and strategies used, and the approach to those topics was relatively superficial. Existing workshops have covered topics such as the standard structure of articles, publication ethics, techniques for improving publication rates, and how to use the English language. However, many other topics are left uncovered. The reports and practice of academic-teaching courses should be improved.

When interpreting results and drawing conclusions, authors of systematic reviews should consider the limitations of the evidence included in their review. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach provides a framework for the explicit consideration of the limitations of the evidence included in a systematic review, and for incorporating this assessment into the conclusions. Assessments of certainty of evidence are a methodological expectation of systematic reviews. The certainty of the evidence is specific to each outcome in a systematic review, and can be rated as high, moderate, low, or very low. Because it will have an important impact, before conducting certainty of evidence, reviewers must clarify the intent of their question: are they interested in causation or association. Serious concerns regarding limitations in the study design, inconsistency, imprecision, indirectness, and publication bias can decrease the certainty of the evidence. Using an example, this article describes and illustrates the importance and the steps for assessing the certainty of evidence and drawing accurate conclusions in a systematic review., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Network meta-analysis (NMA), a statistical technique that allows systematic reviewers to simultaneously compare more than two alternatives, makes use of indirect evidence from studies comparing interventions of interest to a common comparator. The capacity for multiple simultaneous comparisons makes NMA appealing for evidence-based decision-makers. This article, aimed at users of SRs with NMAs and at those who are considering conducting SRs with NMAs, provides an introductory level overview of this topic. We describe the main considerations that those conducting systematic reviews with NMA should bear in mind, including decisions regarding grouping interventions into analysis nodes, and testing the assumptions that assure the validity of NMA. We explain and illustrate how both systematic reviewers and users should draw conclusions from NMA that are appropriate and useful for decision-making. Finally, we provide a list of tools that facilitate the conduct and interpretation of NMAs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: We evaluated the comparative effectiveness of all intra-articular injection corticosteroids for treating internal temporomandibular joint (TMJ) disorders. Methods : We searched MEDLINE, CENTRAL, EMBASE, SCOPUS, and LILACS through December 2023. We included randomized clinical trials (RCTs) enrolling patients with symptomatic internal disorders of the TMJ comparing any type of intra-articular corticosteroid therapy against another or to another minimally invasive therapy. The outcomes of interest were pain, range of mandibular motion (RoM), quality of life (QoL) and adverse effects at 1, 3, 6, and 12 months. We assessed the risk of bias using the Cochrane Collaboration's tool. We conducted a frequentist network meta-analysis and assessed the certainty of the evidence (CoE) using GRADE. Results : We included 20 RCTs enrolling 810 participants, which assessed five corticosteroids alone or combined with arthrocentesis or hyaluronic acid. Based on moderate CoE, betamethasone is among the most effective corticosteroids for reducing pain at one (mean difference compared to arthrocentesis [MD], -3.80; 95% confidence interval [CI], -4.55 to -3.05) and three months (MD, -2.74; 95%CI, -3.42 to -2.06), and arthrocentesis plus dexamethasone at six months (MD, -0.80; 95%CI, -1.57 to -0.03). There was no convincing evidence that any intervention was better than arthrocentesis for improving the RoM and QoL at any follow-up time. Methylprednisolone may be more harmful than arthrocentesis for adverse effects. Discussion : Betamethasone and arthrocentesis plus dexamethasone are the most effective in managing pain in the short and medium term compared to arthrocentesis (moderate CoE). Decisions about their use should consider other factors, such as costs, feasibility, and acceptability. Future research should consider QoL as an outcome and assess participants at longer follow-up periods.

Systematic reviews are a type of evidence synthesis in which authors develop explicit eligibility criteria, collect all the available studies that meet these criteria, and summarize results using reproducible methods that minimize biases and errors. Systematic reviews serve different purposes and use a different methodology than other types of evidence synthesis that include narrative reviews, scoping reviews, and overviews of reviews. Systematic reviews can address questions regarding effects of interventions or exposures, diagnostic properties of tests, and prevalence or prognosis of diseases. All rigorous systematic reviews have common processes that include: 1) determining the question and eligibility criteria, including a priori specification of subgroup hypotheses 2) searching for evidence and selecting studies, 3) abstracting data and assessing risk of bias of the included studies, 4) summarizing the data for each outcome of interest, whenever possible using meta-analyses, and 5) assessing the certainty of the evidence and drawing conclusions. There are several tools that can guide and facilitate the systematic review process, but methodological and content expertise are always necessary., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear., Objective: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids., Methods: We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach., Results: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty)., Conclusions: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: An emerging body of randomized controlled trials (RCTs) on COVID-19 vaccines has served as the evidence base for public health decision-making. While it is recommended that RCTs report results by health equity stratifiers to reduce bias in health care and gaps in research, it is unknown whether this was done in COVID-19 vaccine trials. To critically examine the use of health equity stratifiers in COVID-19 vaccine trials., Study Design and Setting: We conducted a methodological review of published COVID-19 vaccine trials available in the COVID-19 living Network Meta-Analysis systematic review database through February 8, 2023. Based on the PROGRESS-Plus framework, we examined the following health equity stratifiers: place of residence, race/ethnicity, occupation, gender/sex, religion, education, socio-economic status, social capital, age, disability, features of relationships, and temporary situations. We assessed each study in duplicate according to three criteria for comprehensive health-equity reporting: 1) describing participants, 2) reporting equity-relevant results, and 3) discussing equity-relevant implications of trial findings., Results: We reviewed 144 trial manuscripts. The most frequently used PROGRESS-Plus stratifiers to describe participants were age (100%), place of residence (100%), gender/sex (99%), and race/ethnicity (64%). Age was most often used to disaggregate or adjust results (67%), followed by gender or sex (35%). Discussions of equity-relevant implications often indicated limited generalizability of results concerning age (40% of studies). Half (47%) of the studies considered at least one health equity stratifier for all three criteria. No trials included stratifiers related to religion, socioeconomic status, sexual orientation, or features of relationships., Conclusion: COVID-19 vaccine trials provided a limited description of health equity stratifiers as defined by PROGRESS-Plus and infrequently disaggregated results or discussed the study implications as they related to health equity. Considering the health disparities exacerbated during the pandemic, increased uptake of PROGRESS-Plus in RCTs would support a more nuanced understanding of health disparities and better inform actions to improve health equity., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare. This study receieved no funding., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hypophosphatasia (HPP) is an inborn error of metabolism caused by reduced or absent activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, resulting from pathogenic variants in the ALPL gene. Clinical presentation of HPP is highly variable, including lethal and severe forms in neonates and infants, a benign perinatal form, mild forms manifesting in adulthood, and odonto-HPP. Diagnosis of HPP remains a challenge in adults, as signs and symptoms may be mild and non-specific. Disease presentation varies widely; there are no universal signs or symptoms, and the disease often remains underdiagnosed or misdiagnosed, particularly by clinicians who are not familiar with this rare disorder. The absence of diagnosis or a delayed diagnosis may prevent optimal management for patients with this condition. Formal guidelines for the diagnosis of adults with HPP do not exist, complicating efforts for consistent diagnosis. To address this issue, the HPP International Working Group selected 119 papers that explicitly address the diagnosis of HPP in adults through a Medline, Medline In-Process, and Embase search for the terms "hypophosphatasia" and "HPP," and evaluated the pooled prevalence of 17 diagnostic characteristics, initially selected by a group of HPP clinical experts, in eligible studies and in patients included in these studies. Six diagnostic findings showed a pooled prevalence value over 50% and were considered for inclusion as major diagnostic criteria. Based on these results and according to discussion and consideration among members of the Working Group, we finally defined four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. Authors suggested the integrated use of the identified major and minor diagnostic criteria, which either includes two major criteria, or one major criterion and two minor criteria, for the diagnosis of HPP in adults., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: This manuscript provides a summary of the current evidence to support the criteria for diagnosing a child or adult with hypophosphatasia (HPP). The diagnosis of HPP is made on the basis of integrating clinical features, laboratory profile, radiographic features of the condition, and DNA analysis identifying the presence of a pathogenic variant of the tissue nonspecific alkaline phosphatase gene (ALPL). Often, the diagnosis of HPP is significantly delayed in both adults and children, and updated diagnostic criteria are required to keep pace with our evolving understanding regarding the relationship between ALPL genotype and associated HPP clinical features., Methods: An International Working Group (IWG) on HPP was formed, comprised of a multidisciplinary team of experts from Europe and North America with expertise in the diagnosis and management of patients with HPP. Methodologists (Romina Brignardello-Petersen and Gordon Guyatt) and their team supported the IWG and conducted systematic reviews following the GRADE methodology, and this provided the basis for the recommendations., Results: The IWG completed systematic reviews of the literature, including case reports and expert opinion papers describing the phenotype of patients with HPP. The published data are largely retrospective and include a relatively small number of patients with this rare condition. It is anticipated that further knowledge will lead to improvement in the quality of genotype-phenotype reporting in this condition., Conclusion: Following consensus meetings, agreement was reached regarding the major and minor criteria that can assist in establishing a clinical diagnosis of HPP in adults and children., (© 2023. Crown.)

Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present., (© 2023. The Author(s).)

Objectives: To investigate the impact of potential risk of bias elements on effect estimates in randomized trials., Study Design and Setting: We conducted a systematic survey of meta-epidemiological studies examining the influence of potential risk of bias elements on effect estimates in randomized trials. We included only meta-epidemiological studies that either preserved the clustering of trials within meta-analyses (compared effect estimates between trials with and without the potential risk of bias element within each meta-analysis, then combined across meta-analyses; between-trial comparisons), or preserved the clustering of substudies within trials (compared effect estimates between substudies with and without the element, then combined across trials; within-trial comparisons). Separately for studies based on between- and within-trial comparisons, we extracted ratios of odds ratios (RORs) from each study and combined them using a random-effects model. We made overall inferences and assessed certainty of evidence based on Grading of Recommendations, Assessment, development, and Evaluation and Instrument to assess the Credibility of Effect Modification Analyses., Results: Forty-one meta-epidemiological studies (34 of between-, 7 of within-trial comparisons) proved eligible. Inadequate random sequence generation (ROR 0.94, 95% confidence interval [CI] 0.90-0.97) and allocation concealment (ROR 0.92, 95% CI 0.88-0.97) probably lead to effect overestimation (moderate certainty). Lack of patients blinding probably overestimates effects for patient-reported outcomes (ROR 0.36, 95% CI 0.28-0.48; moderate certainty). Lack of blinding of outcome assessors results in effect overestimation for subjective outcomes (ROR 0.69, 95% CI 0.51-0.93; high certainty). The impact of patients or outcome assessors blinding on other outcomes, and the impact of blinding of health-care providers, data collectors, or data analysts, remain uncertain. Trials stopped early for benefit probably overestimate effects (moderate certainty). Trials with imbalanced cointerventions may overestimate effects, while trials with missing outcome data may underestimate effects (low certainty). Influence of baseline imbalance, compliance, selective reporting, and intention-to-treat analysis remain uncertain., Conclusion: Failure to ensure random sequence generation or adequate allocation concealment probably results in modest overestimates of effects. Lack of patients blinding probably leads to substantial overestimates of effects for patient-reported outcomes. Lack of blinding of outcome assessors results in substantial effect overestimation for subjective outcomes. For other elements, though evidence for consistent systematic overestimate of effect remains limited, failure to implement these safeguards may still introduce important bias., Competing Interests: Declaration of competing interest SA, DB, PR, KFS, DZ, and GHG are coauthors of one or more meta-epidemiological studies that this systematic survey included. This work was supported by the Einstein Foundation Berlin as part of the Einstein Foundation Award for Promoting Quality in Research. The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement by, the Einstein Foundation or the award jury. Authors do not have any personal financial interests or professional relationships related to the subject matter but not directly to this manuscript. There are no patents or copyrights licensed to the author(s) that are relevant to the work submitted for publication. No additional relationships or activities to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Combining multivariate and network meta-analysis methods simultaneously in a multivariate network meta-analysis (MVNMA) provides the methodological framework to analyze the largest amount of evidence relevant to decision-makers (i.e. from indirect evidence and correlated outcomes). The objectives of this scoping review were to summarize the characteristics of MVNMAs published in the health sciences literature, and map the methodological guidance available for MVNMA., Study Design and Setting: We searched MEDLINE, EMBASE, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to 28 August 2023, along with citations of included studies, for quantitative evidence syntheses that applied MVNMA and articles addressing MVNMA methods. Pairs of reviewers independently screened potentially eligible studies. Collected data included bibliographic, methodological and analytical characteristics of included studies. We reported results as total numbers, frequencies and percentages for categorical variables, and medians and interquartile ranges for continuous variables that were not normally distributed., Results: After screening 1,075 titles and abstracts, and 112 full texts, we included 38 unique studies; of which, 10 were quantitative evidence syntheses that applied MVNMA and 28 were articles addressing MVNMA methods. Among the 10 MVNMAs, the first was published in 2013, four used studies identified from already published systematic reviews and eight addressed pharmacological interventions, which were the most common interventions. They evaluated interventions for metastatic melanoma, colorectal cancer, prostate cancer, oral hygiene, disruptive behaviour disorders, rheumatoid arthritis, narcolepsy, type 2 diabetes and overactive bladder syndrome. Five MVNMAs analyzed two outcomes simultaneously and four MVNMAs analyzed three outcomes simultaneously. Among the articles addressing MVNMA methods, the first was published in 2007 and the majority provided methodological frameworks for conducting MVNMAs (26/28, 93%). One study proposed criteria to standardize reporting of MVNMAs and two proposed items relevant to the quality assessment of MVNMAs. Study authors used data from 19 different illnesses to provide illustrative examples within their methodological guidance., Conclusions: The application of MVNMA in the health sciences literature is uncommon. Many methodological frameworks are published; however, standardization, and specific criteria to guide reporting and quality assessment are lacking. This overview of the current landscape may help inform future conduct of MVNMAs and research on MVNMA methods., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2023. Published by Elsevier Inc.)