Recommendations on self-management interventions for adults living with obesity: COMPAR-EU project.

Self-management interventions (SMIs) may improve disease management in adults living with obesity. We formulated evidence-based recommendations for SMIs within the context of the COMPAR-EU project. The multidisciplinary panel selected critical outcomes based on the COMPAR-EU core outcome set and established decision thresholds for each outcome. Recommendations were informed by systematic reviews of effects, cost-effectiveness, and a contextual assessment. To assess the certainty of the evidence and formulate the recommendations, we used the GRADE approach guidance. Overall, SMIs were deemed to have a small impact, but the absence of harmful effects and potential cumulative benefits indicated a favourable balance of effects, despite low certainty. SMIs showed variations in structure, intensity, and resource utilisation, but overall are likely to be cost-effective. Adapting SMIs to local contexts would enhance equity, acceptability, and feasibility, considering patients' values, and availability of resources and teamwork. Consequently, the panel made conditional recommendations favouring SMIs over usual care. The rigorous and explicit recommendations demonstrated the effectiveness of SMIs for adults living with obesity. However, the gaps in the literature influenced the panel to make only conditional recommendations in favour of SMIs. Further research is needed to strengthen the evidence base and improve recommendations' certainty and applicability.

Synthesis methods used to combine observational studies and randomised trials in published meta-analyses.

BACKGROUND: This study examined the synthesis methods used in meta-analyses pooling data from observational studies (OSs) and randomised controlled trials (RCTs) from various medical disciplines. METHODS: We searched Medline via PubMed to identify reports of systematic reviews of interventions, including and pooling data from RCTs and OSs published in 110 high-impact factor general and specialised journals between 2015 and 2019. Screening and data extraction were performed in duplicate. To describe the synthesis methods used in the meta-analyses, we considered the first meta-analysis presented in each article. RESULTS: Overall, 132 reports were identified with a median number of included studies of 14 [9-26]. The median number of OSs was 6.5 [3-12] and that of RCTs was 3 [1-6]. The effect estimates recorded from OSs (i.e., adjusted or unadjusted) were not specified in 82% (n = 108) of the meta-analyses. An inverse-variance common-effect model was used in 2% (n = 3) of the meta-analyses, a random-effects model was used in 55% (n = 73), and both models were used in 40% (n = 53). A Poisson regression model was used in 1 meta-analysis, and 2 meta-analyses did not report the model they used. The mean total weight of OSs in the studied meta-analyses was 57.3% (standard deviation, ± 30.3%). Only 44 (33%) meta-analyses reported results stratified by study design. Of them, the results between OSs and RCTs had a consistent direction of effect in 70% (n = 31). Study design was explored as a potential source of heterogeneity in 79% of the meta-analyses, and confounding factors were investigated in only 10% (n = 13). Publication bias was assessed in 70% (n = 92) of the meta-analyses. Tau-square was reported in 32 meta-analyses with a median of 0.07 [0-0.30]. CONCLUSION: The inclusion of OSs in a meta-analysis on interventions could provide useful information. However, considerations of several methodological and conceptual aspects of OSs, that are required to avoid misleading findings, were often absent or insufficiently reported in our sample.

COMPAR-EU Recommendations on Self-Management Interventions in Type 2 Diabetes Mellitus.

Self-management interventions (SMIs) offer a promising approach to actively engage patients in the management of their chronic diseases. Within the scope of the COMPAR-EU project, our goal is to provide evidence-based recommendations for the utilisation and implementation of SMIs in the care of adult individuals with type 2 diabetes mellitus (T2DM). A multidisciplinary panel of experts, utilising a core outcome set (COS), identified critical outcomes and established effect thresholds for each outcome. The panel formulated recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, a transparent and rigorous framework for developing and presenting the best available evidence for the formulation of recommendations. All recommendations are based on systematic reviews (SR) of the effects and of values and preferences, a contextual analysis, and a cost-effectiveness analysis. The COMPAR-EU panel is in favour of using SMIs rather than usual care (UC) alone (conditional, very low certainty of the evidence). Furthermore, the panel specifically is in favour of using ten selected SMIs, rather than UC alone (conditional, low certainty of the evidence), mostly encompassing education, self-monitoring, and behavioural techniques. The panel acknowledges that, for most SMIs, moderate resource requirements exist, and cost-effectiveness analyses do not distinctly favour either the SMI or UC. Additionally, it recognises that SMIs are likely to enhance equity, deeming them acceptable and feasible for implementation.

Effectiveness and Cost-Effectiveness of Self-Management Interventions for Adults Living with Heart Failure to Improve Patient-Important Outcomes: An Evidence Map of Randomized Controlled Trials.

Self-management interventions (SMIs) may enhance heart failure (HF) outcomes and address challenges associated with disease management. This study aims to review randomized evidence and identify knowledge gaps in SMIs for adult HF patients. Within the COMPAR-EU project, from 2010 to 2018, we conducted searches in the databases MEDLINE, CINAHL, Embase, Cochrane, and PsycINFO. We performed a descriptive analysis using predefined categories and developed an evidence map of randomized controlled trials (RCTs). We found 282 RCTs examining SMIs for HF patients, comparing two to four interventions, primarily targeting individual patients (97%) globally (34 countries, only 31% from an European country). These interventions involved support techniques such as information sharing (95%) and self-monitoring (62%), often through a mix of in-person and remote sessions (43%). Commonly assessed outcomes included quality of life, hospital admissions, mortality, exercise capacity, and self-efficacy. Few studies have focused on lower socio-economic or minority groups. Nurses (68%) and physicians (30%) were the primary providers, and most studies were at low risk of bias in generating a random sequence for participant allocation; however, the reporting was noticeably unclear of methods used to conceal the allocation process. Our analysis has revealed prevalent support techniques and delivery methods while highlighting methodological challenges. These findings provide valuable insights for researchers, clinicians, and policymakers striving to optimize SMIs for individuals living with HF.

Rapid antigen-based and rapid molecular tests for the detection of SARS-CoV-2: a rapid review with network meta-analysis of diagnostic test accuracy studies.

BACKGROUND: The global spread of COVID-19 created an explosion in rapid tests with results in < 1 hour, but their relative performance characteristics are not fully understood yet. Our aim was to determine the most sensitive and specific rapid test for the diagnosis of SARS-CoV-2. METHODS: Design: Rapid review and diagnostic test accuracy network meta-analysis (DTA-NMA). ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies assessing rapid antigen and/or rapid molecular test(s) to detect SARS-CoV-2 in participants of any age, suspected or not with SARS-CoV-2 infection. INFORMATION SOURCES: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials, up to September 12, 2021. OUTCOME MEASURES: Sensitivity and specificity of rapid antigen and molecular tests suitable for detecting SARS-CoV-2. Data extraction and risk of bias assessment: Screening of literature search results was conducted by one reviewer; data abstraction was completed by one reviewer and independently verified by a second reviewer. Risk of bias was not assessed in the included studies. DATA SYNTHESIS: Random-effects meta-analysis and DTA-NMA. RESULTS: We included 93 studies (reported in 88 articles) relating to 36 rapid antigen tests in 104,961 participants and 23 rapid molecular tests in 10,449 participants. Overall, rapid antigen tests had a sensitivity of 0.75 (95% confidence interval 0.70-0.79) and specificity of 0.99 (0.98-0.99). Rapid antigen test sensitivity was higher when nasal or combined samples (e.g., combinations of nose, throat, mouth, or saliva samples) were used, but lower when nasopharyngeal samples were used, and in those classified as asymptomatic at the time of testing. Rapid molecular tests may result in fewer false negatives than rapid antigen tests (sensitivity: 0.93, 0.88-0.96; specificity: 0.98, 0.97-0.99). The tests with the highest sensitivity and specificity estimates were the Xpert Xpress rapid molecular test by Cepheid (sensitivity: 0.99, 0.83-1.00; specificity: 0.97, 0.69-1.00) among the 23 commercial rapid molecular tests and the COVID-VIRO test by AAZ-LMB (sensitivity: 0.93, 0.48-0.99; specificity: 0.98, 0.44-1.00) among the 36 rapid antigen tests we examined. CONCLUSIONS: Rapid molecular tests were associated with both high sensitivity and specificity, while rapid antigen tests were mainly associated with high specificity, according to the minimum performance requirements by WHO and Health Canada. Our rapid review was limited to English, peer-reviewed published results of commercial tests, and study risk of bias was not assessed. A full systematic review is required. REVIEW REGISTRATION: PROSPERO CRD42021289712.

Empirical evaluation of the methods used in systematic reviews including observational studies and randomized trials.

OBJECTIVES: To examine the methodological characteristics of systematic reviews and meta-analyses including observational studies (OSs) and randomized controlled trials (RCTs), in various medical disciplines. STUDY DESIGN AND SETTING: We searched Medline via PubMed to identify systematic reviews of interventions including RCTs and OSs published in 110 journals from 2015 to 2019. We extracted in duplicate general and methodological characteristics of the systematic review. RESULTS: We identified 402 systematic reviews. Only 39% (n = 160) of them reported the availability of a pre-established protocol. A rationale for including observational data in the systematic review was clearly reported in 25% (n = 102) of the systematic reviews. Thirty two percent (n = 130) of the reviews reported a search strategy intending to identify published and unpublished data for RCTs and OSs. The risk of bias of the individual studies was assessed in 89% (n = 359) of the systematic reviews. In 74% (n = 266) it was assessed for both RCTs and OSs; 180 (50%) used different tools. Information about confounding factors was reported in only 11% of systematic reviews and the type of effect estimates (crude or adjusted) used was specified in only 22% of the systematic reviews. Among the 385 systematic reviews that performed data synthesis, only 132 (33%) pooled OSs and RCTs in the same meta-analysis. CONCLUSION: Including OSs in systematic reviews of interventions could provide useful information but such an approach could also be misleading; thus, several methodological details are needed to ensure appropriate handling of OS and valid results. Our study revealed, although, that substantial methodological information is missing in reports published in high-impact factor general and specialty journals.

Graphical tools for visualizing the results of network meta-analysis of multicomponent interventions.

Network meta-analysis (NMA) is an established method for assessing the comparative efficacy and safety of competing interventions. It is often the case that we deal with interventions that consist of multiple, possibly interacting, components. Examples of interventions' components include characteristics of the intervention, mode (face-to-face, remotely etc.), location (hospital, home etc.), provider (physician, nurse etc.), time of communication (synchronous, asynchronous etc.) and other context related components. Networks of multicomponent interventions are typically sparse and classical NMA inference is not straightforward and prone to confounding. Ideally, we would like to disentangle the effect of each component to find out what works (or does not work). To this aim, we propose novel ways of visualizing the NMA results, describe their use, and illustrate their application in real-life examples. We developed an R package viscomp to produce all the suggested figures.

Exploring the Effectiveness of Self-Management Interventions in Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Chronic diseases are a leading cause of global morbidity and mortality. In response to this challenge, self-management interventions (SMIs) have emerged as an essential tool in improving patient outcomes. However, the diverse and complex nature of SMIs pose significant challenges in measuring their effectiveness. This work aims to investigate the comparative effectiveness of SMIs on Type 2 diabetes mellitus (T2DM) outcomes. METHODS: A rigorous analytical framework was employed to assess the relative effectiveness of different SMIs, encompassing both pairwise and network meta-analysis (NMA), as well as component network meta-analysis (CNMA). Various outcomes were considered, including glycated hemoglobin (HbA1c) control, body mass index (BMI) reduction and low-density lipoprotein (LDL) cholesterol. Visualization tools were also utilized to enhance the interpretation of results. RESULTS: SMIs were found promising in improving clinical outcomes and patient-reported measures. However, considerable heterogeneity and inconsistency across studies challenged the validity of NMA results. CNMA along with various visualization tools offered insights into the contributions of individual SMI components, highlighting the complexity of these interventions. DISCUSSION/CONCLUSIONS: SMIs represent a valuable approach to managing chronic conditions, but their effectiveness is context-dependent. Further research is needed to elucidate the contextual factors influencing SMI outcomes. This work contributes to a comprehensive understanding of SMIs' role in T2DM management, aiming to aid decision-makers, clinicians, and patients in selecting tailored interventions.

EAES rapid guideline: updated systematic review, network meta-analysis, CINeMA and GRADE assessment, and evidence-informed European recommendations on the management of common bile duct stones.

BACKGROUND: Choledocholithiasis presents in a considerable proportion of patients with gallbladder disease. There are several management options, including preoperative or intraoperative endoscopic cholangiopancreatography (ERCP), and laparoscopic common bile duct exploration (LCBDE). OBJECTIVE: To develop evidence-informed, interdisciplinary, European recommendations on the management of common bile duct stones in the context of intact gallbladder with a clinical decision to intervene to both the gallbladder and the common bile duct stones. METHODS: We updated a systematic review and network meta-analysis of LCBDE, preoperative, intraoperative, and postoperative ERCP. We formed evidence summaries using the GRADE and the CINeMA methodology, and a panel of general surgeons, gastroenterologists, and a patient representative contributed to the development of a GRADE evidence-to-decision framework to select among multiple interventions. RESULTS: The panel reached unanimous consensus on the first Delphi round. We suggest LCBDE over preoperative, intraoperative, or postoperative ERCP, when surgical experience and expertise are available; intraoperative ERCP over LCBDE, preoperative or postoperative ERCP, when this is logistically feasible in a given healthcare setting; and preoperative ERCP over LCBDE or postoperative ERCP, when intraoperative ERCP is not feasible and there is insufficient experience or expertise with LCBDE (weak recommendation). The evidence summaries and decision aids are available on the platform MAGICapp ( https://app.magicapp.org/#/guideline/nJ5zyL ). CONCLUSION: We developed a rapid guideline on the management of common bile duct stones in line with latest methodological standards. It can be used by healthcare professionals and other stakeholders to inform clinical and policy decisions. GUIDELINE REGISTRATION NUMBER: IPGRP-2022CN170.

AGREE-S: AGREE II extension for surgical interventions: appraisal instrument.

BACKGROUND: The Appraisal of Guidelines Research and Evaluation (AGREE) II instrument was developed to evaluate the quality of clinical practice guidelines. Evidence suggests that development, reporting, and appraisal of guidelines on surgical interventions may be better informed by modification of the instrument. OBJECTIVE: We aimed to develop an AGREE II extension specifically designed for appraisal of guidelines of surgical interventions. METHODS: In a three-part project funded by the United European Gastroenterology and the European Association for Endoscopic Surgery, (i) we identified factors that were associated with higher quality of surgical guidelines, (ii) we statistically calibrated the AGREE II instrument in the context of surgical guidelines using correlation, reliability, and factor analysis, and (iii) we undertook a Delphi consensus process of stakeholders to inform the development of an AGREE II extension instrument for surgical interventions. RESULTS: Several features were prioritized by stakeholders as of particular importance for guidelines of surgical interventions, including development of a guideline protocol, consideration of practice variability and surgical expertise in different settings, and specification of infrastructures required to implement the recommendations. The AGREE-S-AGREE II extension instrument for surgical interventions has 25 items, compared to the 23 items of the original AGREE II instrument, organized into the following 6 domains: Scope and purpose, Stakeholders, Evidence synthesis, Development of recommendations, Editorial independence, and Implementation and update. As the original instrument, it concludes with an overall appraisal of the quality of the guideline and a judgement on whether the guideline is recommended for use. Several items were amended and rearranged among domains, and an item was deleted. The Rigor of Development domain of the original AGREE II was divided into Evidence Synthesis and Development of Recommendations. Items of the AGREE II domain Clarity of Presentation were incorporated in the new domain Development of Recommendations. Three new items were introduced, addressing the development of a guideline protocol, support by a guideline methodologist, and consideration of surgical experience/expertise. CONCLUSION: The AGREE-S appraisal instrument has been developed to be used for assessment of the methodological and reporting quality of guidelines on surgical interventions.

AGREE-S: AGREE II extension for surgical interventions - United European Gastroenterology and European Association for Endoscopic Surgery methodological guide.

BACKGROUND: The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument has been developed to inform the methodology, reporting and appraisal of clinical practice guidelines. Evidence suggests that the quality of surgical guidelines can be improved, and the structure and content of AGREE II can be modified to help enhance the quality of guidelines of surgical interventions. OBJECTIVE: To develop an extension of AGREE II specifically designed for guidelines of surgical interventions. METHODS: In the tripartite Guideline Assessment Project (GAP) funded by United European Gastroenterology and the European Association for Endoscopic Surgery, (i) we assessed the quality of surgical guidelines and we identified factors associated with higher quality (GAP I); (ii) we applied correlation analysis, factor analysis and the item response theory to inform an adaption of AGREE II for the purposes of surgical guidelines (GAP II); and (iii) we developed an AGREE II extension for surgical interventions, informed by the results of GAP I, GAP II, and a Delphi process of stakeholders, including representation from interventional and surgical disciplines; the Guideline International Network (GIN); the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group; the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) initiative; and representation of surgical journal editors and patient/public. RESULTS: We developed AGREE-S, an AGREE II extension for surgical interventions, which comprises 24 items organized in 6 domains; Scope and purpose, Stakeholders, Evidence synthesis, Development of recommendations, Editorial independence, and Implementation and update. The panel of stakeholders proposed 3 additional items: development of a guideline protocol, consideration of practice variability and surgical/interventional expertise in different settings, and specification of infrastructures required to implement the recommendations. Three of the existing items were amended, 7 items were rearranged among the domains, and one item was removed. The domain Rigour of Development was divided into domains on Evidence Synthesis and Development of Recommendations. The new domain Development of Recommendations incorporates items from the original AGREE II domain Clarity of Presentation. CONCLUSION: AGREE-S is an evidence-based and stakeholder-informed extension of the AGREE II instrument, that can be used as a guide for the development and adaption of guidelines on surgical interventions.

Diagnostic test accuracy network meta-analysis methods: A scoping review and empirical assessment.

OBJECTIVES: To (a) identify methodological and application papers reporting a model developed specifically for diagnostic test accuracy network meta-analysis (DTA-NMA) or a hierarchical meta-regression method for comparing at least three index tests; (b) review and summarize the characteristics of the methods and the application papers; and (c) compare DTA-NMA and hierarchical meta-regression methods empirically. STUDY DESIGN AND SETTING: We performed a scoping review and searched major databases until March 3rd, 2021. We assessed the characteristics of the identified methods, conducted a descriptive analysis of characteristics of the application articles, and applied the DTA-NMA and meta-regression methods to the available data. RESULTS: We included 49 articles (plus one companion report), of which nine were methodological (describing 11 DTA-NMA methods) and 40 were application papers (data available for 32 DTA-NMAs). Our results showed a steep increase in recent years in DTA-NMA publications. DTA-NMA models may lead to different results. Although sensitivity estimates were comparable between meta-regression and DTA-NMA models, specificity estimates were higher in meta-regression. CONCLUSION: The choice of a DTA-NMA model will depend on the available data, including the use of different thresholds for test positivity, different study designs, and software familiarity. Selection between the methods may impact on the NMA results, especially for specificity.

Biofire FilmArray Meningitis/Encephalitis panel for the aetiological diagnosis of central nervous system infections: A systematic review and diagnostic test accuracy meta-analysis.

BACKGROUND: The FilmArray Meningitis/Encephalitis(FA/ME) panel brings benefits in clinical practice, but its diagnostic test accuracy (DTA) remains unclear. We aimed to determine the DTA of FA/ME for the aetiological diagnostic in patients with suspected central nervous system(CNS) infection. METHODS: We performed a systematic review with DTA meta-analysis (PROSPERO: CRD42020139285). We searched Embase, Medline (Ovid), and Web of Science from inception until September 1st, 2021. We assessed the study-level risk of bias with the QUADAS-2 tool and applied the GRADE approach to assess the certainty of the synthesised evidence. We included studies that simultaneously measured the reference test (CSF/blood culture for bacteria, and specific polymerase chain reaction for viruses) and the FA/ME in patients with suspected CNS infection. We performed random-effects bivariate meta-analysis models of combined sensitivity and specificity using CSF/blood cultures(reference test 1) and a final diagnosis adjudication based on clinical/laboratory criteria (reference test 2). FINDINGS: We included 19 studies (11,351 participants). For all bacteria with reference test 1 (16 studies/6183 patients) sensitivity was estimated at 89·5% (95%CI 81·1-94·4), and specificity at 97·4% (95%CI 94-98·9). With reference test 2 (15 studies/5,524 patients), sensitivity was estimated at 92·1%(95%CI 86·8-95·3) and specificity at 99.2(95%CI 98·3-99·6) For herpes simplex virus-2(HSV-2), enteroviruses, and Varicella-Zoster virus (VZV), we obtained sensitivities between 75·5 and 93·8%, and specificities above 99% (reference test 1). Certainty of the evidence was low. INTERPRETATION: FA/ME may have acceptable-to-high sensitivities and high specificities for identifying bacteria, especially for S.pneumoniae, and viruses, especially for HSV-2, and enteroviruses. Sensitivities for L.monocytogenes, H.influenzae, E.coli, and HSV-1 were suboptimal. FUNDING: None.

Challenges in Comparative Meta-Analysis of the Accuracy of Multiple Diagnostic Tests.

The rapid increase in diagnostic and screening techniques has urged the need to choose among multiple diagnostic tests. For the majority of diseases, there is more than a single test available, and studies usually compare a subset of these tests. In such cases, a separate meta-analysis of each test cannot provide a reliable answer on the relative accuracy of the multiple available tests. Extensions of standard (hierarchical) meta-analysis to network meta-analysis (NMA) models for the comparison of at least three diagnostic tests have been the subject of methodological research in recent years. NMA can be used to jointly analyze the totality of evidence in order to provide estimates of relative accuracy (sensitivity and specificity ), to compare tests that have not been compared head-to-head, and to obtain a ranking of all competing tests in order to further facilitate the decision-making process.In this chapter, we illustrate current methodology for meta-analysis of multiple test comparisons, introduce NMA methods of diagnostic tests as an extension to the standard meta-analysis of diagnostic test accuracy (DTA) studies, and present existing approaches to rank tests according to their accuracy, specificity , and sensitivity . We also describe the basic concepts, underlying assumptions, and challenges in NMA of multiple diagnostic tests.

Prevalence of evidence of inconsistency and its association with network structural characteristics in 201 published networks of interventions.

BACKGROUND: Network meta-analysis (NMA) has attracted growing interest in evidence-based medicine. Consistency between different sources of evidence is fundamental to the reliability of the NMA results. The purpose of the present study was to estimate the prevalence of evidence of inconsistency and describe its association with different NMA characteristics. METHODS: We updated our collection of NMAs with articles published up to July 2018. We included networks with randomised clinical trials, at least four treatment nodes, at least one closed loop, a dichotomous primary outcome, and available arm-level data. We assessed consistency using the design-by-treatment interaction (DBT) model and testing all the inconsistency parameters globally through the Wald-type chi-squared test statistic. We estimated the prevalence of evidence of inconsistency and its association with different network characteristics (e.g., number of studies, interventions, intervention comparisons, loops). We evaluated the influence of the network characteristics on the DBT p-value via a multivariable regression analysis and the estimated Pearson correlation coefficients. We also evaluated heterogeneity in NMA (consistency) and DBT (inconsistency) random-effects models. RESULTS: We included 201 published NMAs. The p-value of the design-by-treatment interaction (DBT) model was lower than 0.05 in 14% of the networks and lower than 0.10 in 20% of the networks. Networks including many studies and comparing few interventions were more likely to have small DBT p-values (less than 0.10), which is probably because they yielded more precise estimates and power to detect differences between designs was higher. In the presence of inconsistency (DBT p-value lower than 0.10), the consistency model displayed higher heterogeneity than the DBT model. CONCLUSIONS: Our findings show that inconsistency was more frequent than what would be expected by chance, suggesting that researchers should devote more resources to exploring how to mitigate inconsistency. The results of this study highlight the need to develop strategies to detect inconsistency (because of the relatively high prevalence of evidence of inconsistency in published networks), and particularly in cases where the existing tests have low power.