GRADE guidance 37: rating imprecision in a body of evidence on test accuracy.

OBJECTIVES: To provide guidance on rating imprecision in a body of evidence assessing the accuracy of a single test. This guide will clarify when Grading of Recommendations Assessment, Development and Evaluation (GRADE) users should consider rating down the certainty of evidence by one or more levels for imprecision in test accuracy. STUDY DESIGN AND SETTING: A project group within the GRADE working group conducted iterative discussions and presentations at GRADE working group meetings to produce this guidance. RESULTS: Before rating the certainty of evidence, GRADE users should define the target of their certainty rating. GRADE recommends setting judgment thresholds defining what they consider a very accurate, accurate, inaccurate, and very inaccurate test. These thresholds should be set after considering consequences of testing and effects on people-important outcomes. GRADE's primary criterion for judging imprecision in test accuracy evidence is considering confidence intervals (i.e., CI approach) of absolute test accuracy results (true and false, positive, and negative results in a cohort of people). Based on the CI approach, when a CI appreciably crosses the predefined judgment threshold(s), one should consider rating down certainty of evidence by one or more levels, depending on the number of thresholds crossed. When the CI does not cross judgment threshold(s), GRADE suggests considering the sample size for an adequately powered test accuracy review (optimal or review information size [optimal information size (OIS)/review information size (RIS)]) in rating imprecision. If the combined sample size of the included studies in the review is smaller than the required OIS/RIS, one should consider rating down by one or more levels for imprecision. CONCLUSION: This paper extends previous GRADE guidance for rating imprecision in single test accuracy systematic reviews and guidelines, with a focus on the circumstances in which one should consider rating down one or more levels for imprecision.

Self-efficacy measurement instruments for individuals with coronary artery disease: A systematic review.

INTRODUCTION: Over the past decade, there has been a heightened interest in evaluating self-efficacy among patients with coronary artery disease (CAD). A significant number of instruments have been developed and validated, yet the need remains to assess the quality of their studies and their properties. OBJECTIVES: To evaluate the measurement properties and link the content extracted from self-efficacy instrument items for individuals with CAD to the International Classification of Functioning, Disability, and Health (ICF). METHODOLOGY: The study was conducted following the Cochrane systematic review guidelines and COnsensus norms for Selection of health Measuring INstruments (COSMIN), registered under CRD42021262613. The search was carried out on MEDLINE (Ovid), Web of Science, EMBASE, and PsycINFO, including studies involving the development and validation of self-efficacy instruments for individuals with CAD, without language or date restrictions. Data extraction was performed in May 2022 and updated in January 2023 and all the steps of this review were carried out by two different collaborators and reviewed by a third when there were divergences. Modified Grading of Recommendations, Assessment, Development and Evaluation (GRADE) recommended by COSMIN was used to determine the quality of evidence as high, moderate, low, or very low. Instrument categorization was carried out per COSMIN recommendations, according to the construct of interest and study population into three categories (A, B, or C). RESULTS: A total of 21 studies from 12 instruments were identified. The best-rated instruments received a recommendation of B, which means, additional validation studies are needed. Barnason Efficacy Expectation Scale (BEES) showed high-quality evidence for structural, construct, criterion, and internal consistency validity; Cardiac Self-Efficacy Scale (CSES) demonstrated high quality for content, structural, cross-cultural validity, and internal consistency; Self-efficacy for Appropriate Medication Use (SEAMS) achieved a high level for structural, criterion, and internal consistency validity; Cardiovascular Management Self-Efficacy Scale exhibited high-level validity for structural, criterion, construct, and internal consistency. The CSES showed content linkage with all domains of the ICF, as well as the highest number of linkages with the categories. CONCLUSIONS: Instruments with a B-level recommendation hold potential for use. More studies assessing measurement properties are needed to reinforce or improve these recommendations. The CSES stands out as the most comprehensive instrument concerning the ICF.

GRADE pearls and pitfalls-Part 1: Systematic reviews and meta-analyses.

BACKGROUND: The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach is used to assess the certainty of evidence in systematic reviews and meta-analyses. METHODS: We describe how the GRADE approach is used in systematic reviews and meta-analyses, including key points and examples. This overview is aimed at clinicians and researchers who are, or plan to be, involved in the development or assessment of systematic reviews with meta-analyses using GRADE. RESULTS: We outline how the certainty of evidence is assessed, how the evidence is summarized using GRADE evidence profiles or summary of findings tables, how the results are communicated, and we discuss challenges, advantages, and disadvantages with using GRADE. CONCLUSIONS: This overview aims to provide an overview of how GRADE is used in systematic reviews and meta-analyses, and may be used by systematic review developers, methodologists, and evidence end-users.

GRADE pearls and pitfalls-Part 2: Clinical practice guidelines.

BACKGROUND: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is the de facto standard framework for summarising evidence in systematic reviews and developing recommendations in clinical practice guidelines. METHODS: We describe how the GRADE approach is used in clinical practice guidelines, including key points and examples. The intended audience of this overview of GRADE is clinicians and researchers who are, or plan to be, involved in the development or assessment of clinical practice guidelines. RESULTS: We cover guideline endorsement and adaptation; guideline panels and sponsors; conflicts of interest; guideline questions and outcome prioritisation; systematic review creation, updating and re-use; rating the overall certainty of evidence; development of recommendations and implications; and peer review, publication, implementation and updating of guidelines. CONCLUSIONS: This overview aims to help developers, assessors and users of clinical practice guidelines understand how trustworthy, high-quality guidelines are developed using the GRADE approach.

Biopathologic Characterization and Grade Assessment of Breast Cancer With 3-D Multiparametric Ultrasound Combining Shear Wave Elastography and Backscatter Tensor Imaging.

OBJECTIVE: Despite recent improvements in medical imaging, the final diagnosis and biopathologic characterization of breast cancers currently still requires biopsies. Ultrasound is commonly used for clinical examination of breast masses. B-Mode and shear wave elastography (SWE) are already widely used to detect suspicious masses and differentiate benign lesions from cancers. But additional ultrasound modalities such as backscatter tensor imaging (BTI) could provide relevant biomarkers related to tissue organization. Here we describe a 3-D multiparametric ultrasound approach applied to breast carcinomas in the aims of (i) validating the ability of BTI to reveal the underlying organization of collagen fibers and (ii) assessing the complementarity of SWE and BTI to reveal biopathologic features of diagnostic interest. METHODS: Three-dimensional SWE and BTI were performed ex vivo on 64 human breast carcinoma samples using a linear ultrasound probe moved by a set of motors. Here we describe a 3-D multiparametric representation of the breast masses and quantitative measurements combining B-mode, SWE and BTI. RESULTS: Our results reveal for the first time that BTI can capture the orientation of the collagen fibers around tumors. BTI was found to be a relevant marker for assessing cancer stages, revealing a more tangent tissue orientation for in situ carcinomas than for invasive cancers. In invasive cases, the combination of BTI and SWE parameters allowed for classification of invasive tumors with respect to their grade with an accuracy of 95.7%. CONCLUSION: Our results highlight the potential of 3-D multiparametric ultrasound imaging for biopathologic characterization of breast tumors.

Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment.

BACKGROUND: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. RESULTS: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. LIMITATIONS: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. CONCLUSIONS: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.

Effect of aquatic exercise programs according to the International Classification of Functionality, Disability and Health domains in individuals with Parkinson's disease: a systematic review and meta-analysis with GRADE quality assessment.

PURPOSE: To investigate the effects of aquatic exercise programs (AEP) in body structure and function, activity, and participation outcomes in individuals with Parkinson's disease (PD) with mild to moderate disability levels. METHODS: Six databases were searched from inception until November 2022. Randomized clinical trials that used AEP alone, AEP combined and/or compared two types of AEP were included. The quality of evidence was assessed by the GRADE approach and the standardized mean differences (SMD) were calculated the meta-analysis. RESULTS: Twelve studies (n = 380) were included. AEP alone was superior to active control in improving body structure and function outcome: postural balance (low evidence, SMD = 0.47, p = 0.02). No statistically significant differences were found for the other body structure and function outcomes: lower limb muscle strength (p = 0.14) and depressive symptoms (p = 0.79), activity outcomes: mobility (p = 0.32) and participation outcomes: quality of life (p = 0.05). AEP combined showed no statistically significant difference for the outcomes of body structure and function: postural balance (p = 0.11) and activity: mobility (p = 0.21) when compared to active control. CONCLUSION: AEP showed positive effects on body structure and function outcome (postural balance) in individuals with PD with mild to moderate disability levels while, no significant improvements were noticed for activity and participation outcomes.IMPLICATIONS FOR REHABILITATIONOur findings indicate that aquatic exercise programs (AEP) lead to significant improvements on body structure and function (i.e., postural balance) in individuals with Parkinson's disease (PD).The AEP evaluated in this study implemented postural balance, gait, single and double training, as well as aerobic exercises, trunk mobility exercises, and Ai Chi.The average duration, frequency, and total time implemented were 50 minutes, three times a week, for seven weeks, respectively.Considering the potential benefits identified in this study, AEP can be recommended as an adjunct treatment strategy for individuals with PD.Additionally, the use of the International Classification of Functionality, Disability and Health on the development of rehabilitation treatment plans is advised.

EAES Multidisciplinary Rapid Guideline: systematic review, meta-analysis, GRADE assessment and evidence-informed recommendations on the surgical management of paraesophageal hernias.

BACKGROUND: New evidence has emerged since latest guidelines on the management of paraesophageal hernia, and guideline development methodology has evolved. Members of the European Association for Endoscopic Surgery have prioritized the management of paraesophageal hernia to be addressed by pertinent recommendations. OBJECTIVE: To develop evidence-informed clinical practice recommendations on paraesophageal hernias, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: We performed three systematic reviews, and we summarized and appraised the certainty of the evidence using the GRADE methodology. A panel of general and upper gastrointestinal surgeons, gastroenterologists and a patient advocate discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost and use of resources, moderated by a Guidelines International Network-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests surgery over conservative management for asymptomatic/minimally symptomatic paraesophageal hernias (conditional recommendation), and recommends conservative management over surgery for asymptomatic/minimally symptomatic paraesophageal hernias in frail patients (strong recommendation). Further, the panel suggests mesh over sutures for hiatal closure in paraesophageal hernia repair, fundoplication over gastropexy in elective paraesophageal hernia repair, and gastropexy over fundoplication in patients who have cardiopulmonary instability and require emergency paraesophageal hernia repair (conditional recommendation). A strong recommendation means that the proposed course of action is appropriate for the vast majority of patients. A conditional recommendation means that most patients would opt for the proposed course of action, and joint decision-making of the surgeon and the patient is required. Accompanying evidence summaries and evidence-to-decision frameworks should be read when using the recommendations. This guideline applies to adult patients with moderate to large paraesophageal hernias type II to IV with at least 50% of the stomach herniated to the thoracic cavity. The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/j7q7Gn . CONCLUSION: An interdisciplinary panel provides recommendations on key topics on the management of paraesophageal hernias using highest methodological standards and following a transparent process. GUIDELINE REGISTRATION NUMBER: PREPARE-2023CN018.

Guidelines for the diagnosis and treatment of basal cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.

GRADE concept 6: a novel application of external indirect evidence into GRADE ratings of evidence certainty in network meta-analysis.

OBJECTIVES: We describe how consideration of external evidence may play an important role in judging certainty in the process of establishing the certainty of the evidence. Our example is a network meta-analysis (NMA) addressing treatment for Ebola virus disease, which informed a World Health Organization guideline. STUDY DESIGN AND SETTING: Through Grading of Recommendations Assessment, Development, and Evaluations (GRADE) project group iterative online, in-person and email discussions, we developed this GRADE concept and obtained approval from the GRADE working group. Using the null as a threshold, we rated our certainty for network estimates in mortality, including consideration of evidence external to the NMA (i.e., did not meet eligibility criteria) and formal logical construction. RESULTS: Based on the existing GRADE guidance, we rated the network estimate for one indirect comparison as low certainty. The formal logical construction that lead us reevaluate the certainty of the evidence is as follows: if A is superior to B, and B is not inferior to C, then A must be superior to C. After considering the logic and the external indirect evidence, we concluded at least moderate certainty for the comparison. CONCLUSION: Systematic review authors and guideline developers should apply the fundamental logical construction for indirect comparisons and consider compelling external evidence in NMA certainty ratings.

Tramadol for chronic pain in adults: protocol for a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials.

BACKGROUND: Chronic pain in adults is a frequent clinical symptom with a significant impact on patient well-being. Therefore, sufficient pain management is of utmost importance. While tramadol is a commonly used pain medication, the quality of evidence supporting its use has been questioned considering the observed adverse events. Our objective will be to assess the benefits and harms of tramadol compared with placebo or no intervention for chronic pain. METHODS/DESIGN: We will conduct a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis to assess the beneficial and harmful effects of tramadol in any dose, formulation, or duration. We will accept placebo or no intervention as control interventions. We will include adult participants with any type of chronic pain, including cancer-related pain. We will systematically search the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and BIOSIS for relevant literature. We will follow the recommendations by Cochrane and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risk of systematic errors ('bias') and random errors ('play of chance') will be assessed. The certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION: Although tramadol is often being used to manage chronic pain conditions, the beneficial and harmful effects of this intervention are unknown. The present review will systematically assess the current evidence on the benefits and harms of tramadol versus placebo or no intervention to inform clinical practice and future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019140334.

GRADE guidance 23: considering cost-effectiveness evidence in moving from evidence to health-related recommendations.

BACKGROUND: This is the 23rd in a series of articles describing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the certainty of evidence and strength of recommendations for systematic reviews, health technology assessments, and clinical guideline development. OBJECTIVES: We outline how resource utilization and cost-effectiveness analyses are integrated into health-related recommendations, using the GRADE Evidence to Decision (EtD) frameworks. STUDY DESIGN AND SETTING: Through iterative discussions and refinement, in-person, and online meetings, and through e-mail communication, we developed draft guidance to incorporate economic evidence in the formulation of health-related recommendations. We developed scenarios to operationalize the guidance. We presented a summary of the results to members of the GRADE Economic Evaluation Project Group. RESULTS: We describe how to estimate the cost of preventing (or achieving) an event to inform assessments of cost-effectiveness of alternative treatments, when there are no published economic evaluations. Evidence profiles and Summary of Findings tables based on systematic reviews of cost-effectiveness analyses can be created to provide top-level summaries of results and quality of multiple published economic evaluations. We also describe how this information could be integrated in GRADE's EtD frameworks to inform health-related recommendations. Three scenarios representing various levels of available cost-effectiveness evidence were used to illustrate the integration process. CONCLUSION: This GRADE guidance provides practical information for presenting cost-effectiveness data and its integration in the development of health-related recommendations, using the EtD frameworks.

Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

The Effects of Lycopene and Tomato Consumption on Cardiovascular Risk Factors in Adults: A Grade Assessment Systematic Review and Meta-analysis.

BACKGROUND: In recent times, modifying dietary habits to control cardiovascular risk factors has gained significant attention. However, previous studies have yielded inconsistent results regarding the effects of lycopene and tomato consumption on cardiovascular risk factors. OBJECTIVE: The objective of this study was to assess the impact of consuming lycopene and tomatoes on various cardiovascular risks factors such as lipid profile, glycemic control markers, blood pressure, inflammation, oxidative stress, and body weight. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, and Scopus, up to November 2022 to identify eligible Randomized Control Trials (RCTs) evaluating the effect of lycopene and tomato consumption on cardiovascular risk factors. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference (WMD) with a 95% confidence interval (CI). RESULTS: Out of 27,438 records initially identified, a total of 34 studies met the eligibility criteria and were included in this meta-analysis. The results showed that lycopene consumption was associated with a significant reduction in malondialdehyde (MDA) levels, indicating a potential benefit in reducing oxidative stress. However, lycopene and tomato consumption did not have significant effects on other cardiovascular risk factors such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), Intercellular Adhesion Molecule 1 (ICAM-1), c-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), body weight, and body mass index (BMI). CONCLUSION: Overall, the findings showed that lycopene and tomato consumption did not affect cardiovascular risk factors. However, lycopene supplementation may result in a significant improvement in MDA levels. With the view to confirming these results, further studies with long-term duration and different doses are needed.

Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Meta-analysis and GRADE assessment of randomized controlled trials on the efficacy and safety of bimekizumab in psoriatic arthritis patients.

OBJECTIVE: A persistent immune-mediated inflammatory disorder called psoriatic arthritis affects about 25% of persons with psoriasis. Bimekizumab, a humanized monoclonal IgG1 antibody, is a novel therapeutic approach that inhibits homodimers and heterodimers of IL-17A and IL-17F by binding to comparable locations in these molecules. Bimekizumab was the subject of a meta-analysis to assess its efficacy and safety in psoriatic arthritis patients. METHODS: All randomized clinical trials were looked up on PubMed, Scopus, and Web of Science. The Systematic Review Accelerator tool was used to screen them, and RevMan was used to analyze them. The Mean Difference (MD) and 95% Confidence Interval (CI) were used to examine continuous data, whereas the Risk Ratio (RR) and 95% CI were used to evaluate dichotomous data. RESULTS: A total of 1364 participants from 4 trials were included in this meta-analysis. The number of participants who met the American College of Rheumatology 50 threshold was significantly higher in the bimekizumab group compared to the placebo group [RR = 4.94, 95% CI (3.73, 6.55), p < .00001]. Psoriasis Area and Severity Index 100 was achieved by significantly more people in the bimekizumab group than in the placebo group [RR = 11.45, 95% CI (6.67, 19.67), p < .00001]. There was no significant difference between the bimekizumab group and the placebo group in terms of treatment-emergent adverse events [RR = 1.08, 95% CI (0.97, 1.21), p = .15]. CONCLUSION: In comparison to a placebo, bimekizumab treatment significantly improved joint and skin efficacy outcomes. Also, its safety results were acceptable.

Similar Outcomes of Web-Based and Face-to-Face Training of the GRADE Approach for the Certainty of Evidence: Randomized Controlled Trial.

BACKGROUND: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach is a system for transparent evaluation of the certainty of evidence used in clinical practice guidelines and systematic reviews. GRADE is a key part of evidence-based medicine (EBM) training of health care professionals. OBJECTIVE: This study aimed to compare web-based and face-to-face methods of teaching the GRADE approach for evidence assessment. METHODS: A randomized controlled trial was conducted on 2 delivery modes of GRADE education integrated into a course on research methodology and EBM with third-year medical students. Education was based on the Cochrane Interactive Learning "Interpreting the findings" module, which had a duration of 90 minutes. The web-based group received the web-based asynchronous training, whereas the face-to-face group had an in-person seminar with a lecturer. The main outcome measure was the score on a 5-question test that assessed confidence interval interpretation and overall certainty of evidence, among others. Secondary outcomes included writing a recommendation for practice and course satisfaction. RESULTS: In all, 50 participants received the web-based intervention, and 47 participants received the face-to-face intervention. The groups did not differ in the overall scores for the Cochrane Interactive Learning test, with a median of 2 (95% CI 1.0-2.0) correct answers for the web-based group and 2 (95% CI 1.3-3.0) correct answers for the face-to-face group. Both groups gave the most correct answers to the question about rating a body of evidence (35/50, 70% and 24/47, 51% for the web-based and face-to-face group, respectively). The face-to-face group better answered the question about the overall certainty of evidence question. The understanding of the Summary of Findings table did not differ significantly between the groups, with a median of 3 correct answers to 4 questions for both groups (P=.352). The writing style for the recommendations for practice also did not differ between the 2 groups. Students' recommendations mostly reflected the strengths of the recommendations and focused on the target population, but they used passive words and rarely mentioned the setting for the recommendation. The language of the recommendations was mostly patient centered. Course satisfaction was high in both groups. CONCLUSIONS: Training in the GRADE approach could be equally effective when delivered asynchronously on the web or face-to-face. TRIAL REGISTRATION: Open Science Framework akpq7; https://osf.io/akpq7/.

Effect of e-health interventions on HIV prevention: a protocol of systematic review and meta-analysis.

BACKGROUND: Global epidemiological data indicates that despite implementation of multiple interventions and significant financial investment, the HIV/AIDS epidemic remained inadequately controlled as of 2020. E-health presents a novel approach in delivering health information and health care and has gained popularity in HIV prevention worldwide. However, evidence on the effectiveness of e-health interventions on HIV prevention among diverse populations remains inadequate. Our study aims to systematically evaluate the effectiveness of varying e-health interventions on HIV prevention, with the objective of providing data support and guidance for the development of future e-health HIV intervention strategies. METHODS: A systematic search of electronic English databases, including MEDLINE through PubMed, Embase, Scopus, and Web of Science, along with three Chinese databases, including National Knowledge Infrastructure (CNKI), Chinese Wanfang Digital Periodicals (WANFANG), and Chinese Science and Technology Periodicals (VIP) database, will be conducted for the period of 1 January 1980 to 31 December 2022. Additionally, gray literature and unpublished trials in trial registers will be searched. Studies aimed at HIV prevention through e-health interventions, with full-text publications available in either English or Chinese, will be included. Study types will be limited to RCT, cluster RCT, and quasi-experiment study. The risk of bias in individual studies will be assessed following the guideline highlighted by the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes will cover cognitive, behavioral, psychological, management, and biological measures of individuals involved in e-health interventions. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Ultimately, a systematic review with meta-analysis will be conducted to compare the effectiveness of e-health interventions among diverse populations. DISCUSSION: This systematic review seeks to establish novel insights into the effectiveness of e-health interventions in diverse populations worldwide. It will inform the design and use of e-health interventions to optimize HIV-related strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022295909.

Grading of recommendations assessment, development, and evaluation concept article 5: addressing intransitivity in a network meta-analysis.

OBJECTIVES: This article describes considerations for addressing intransitivity when assessing the certainty of the evidence from network meta-analysis (NMA) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Intransitivity is induced by effect modification, that is, when the magnitude of the effect between an intervention and outcome differs depending on the level of another factor. STUDY DESIGN AND SETTING: To develop this GRADE concept paper, the lead authors conducted iterative discussions, computer simulations, and presentations to the GRADE project group and at GRADE working group meetings. The GRADE Working Group formally approved the article in July 2022. RESULTS: NMA authors can have a higher or a lower threshold to rate down the certainty of the evidence due to intransitivity, which depends on the extent of their concerns regarding the trustworthiness of indirect comparisons, and their view of the relative problems with rating down excessively or insufficiently. NMA authors should consider three main factors when addressing intransitivity: the credibility of effect modification, the strength of the effect modification, and the distribution of effect modifiers across the direct comparisons. To avoid double counting limitations of the evidence, authors should consider the relationship between intransitivity and other GRADE domains. CONCLUSION: NMA authors face theoretic and pragmatic challenges and in most situations need to assess intransitivity without the availability of empirical data. Thus, explicitness regarding perspective is crucial.

Adherence to the Mediterranean diet and risk of frailty and pre-frailty in elderly adults: A systematic review and dose-response meta-analysis with GRADE assessment.

BACKGROUND: Several studies have explored the association between Mediterranean diet and frailty, but reported inconsistent results. This systematic review and dose-response meta-analysis summarized the existing evidence on the relationship between Mediterranean diet and risk of frailty and pre-frailty in elderly adults. METHODS: A systematic search on MEDLINE (PubMed), Scopus, Institute for Scientific Information (ISI) Web of Science and Google Scholar was conducted up to January 2023. Study selection and data extraction were performed by two reviewers working in parallel. Epidemiologic studies reporting relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for frailty/pre-frailty in relation to Mediterranean diet (as a priori dietary pattern) were considered. The overall effect size was determined using a random effects model. The body of evidence was assessed by the GRADE approach. RESULTS: A total of 19 studies (12 cohorts and 7 cross-sectionals) were included. In cohort studies (89,608 participants/ 12,866 cases), the highest versus lowest category of Mediterranean diet was inversely associated with frailty (RR: 0.66; 95%CI: 0.55, 0.78; I2:52.4%, PQ-test=0.02). This association was also significant in cross-sectional studies with 1093 cases among 13,581 participants (OR: 0.44; 95%CI: 0.28, 0.70; I2:81.8%, PQ-test<0.001). Moreover, each 2-point increase in Mediterranean diet score was related to decreased risk of frailty in cohort (RR: 0.86; 95%CI: 0.80, 0.93) and cross-sectional (OR: 0.79; 95%CI: 0.65, 0.95) studies. Nonlinear association showed a decreasing slope in curve, sharper at high scores for cohort studies and a steadily reduction for cross-sectional studies. The certainty of the evidence was graded as high in both cohort and cross-sectional studies. Combining 4 effect sizes of 4 studies (12,745 participants/ 4363 cases), the highest adherence to Mediterranean diet was linked to a lower risk of pre-frailty, as well (pooled OR: 0.73; 95%CI: 0.61, 0.86; I2:40.9%, PQ-test=0.17). CONCLUSION: Adherence to Mediterranean diet is inversely associated with risk of frailty and pre-frailty in older adults and thus, has a considerable impact on health of this population.