Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

Computer-Aided Diagnosis for Leaving Colorectal Polyps In Situ : A Systematic Review and Meta-analysis.

BACKGROUND: Computer-aided diagnosis (CADx) allows prediction of polyp histology during colonoscopy, which may reduce unnecessary removal of nonneoplastic polyps. However, the potential benefits and harms of CADx are still unclear. PURPOSE: To quantify the benefit and harm of using CADx in colonoscopy for the optical diagnosis of small (≤5-mm) rectosigmoid polyps. DATA SOURCES: Medline, Embase, and Scopus were searched for articles published before 22 December 2023. STUDY SELECTION: Histologically verified diagnostic accuracy studies that evaluated the real-time performance of physicians in predicting neoplastic change of small rectosigmoid polyps without or with CADx assistance during colonoscopy. DATA EXTRACTION: The clinical benefit and harm were estimated on the basis of accuracy values of the endoscopist before and after CADx assistance. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. The outcome measure for benefit was the proportion of polyps predicted to be nonneoplastic that would avoid removal with the use of CADx. The outcome measure for harm was the proportion of neoplastic polyps that would be not resected and left in situ due to an incorrect diagnosis with the use of CADx. Histology served as the reference standard for both outcomes. DATA SYNTHESIS: Ten studies, including 3620 patients with 4103 small rectosigmoid polyps, were analyzed. The studies that assessed the performance of CADx alone (9 studies; 3237 polyps) showed a sensitivity of 87.3% (95% CI, 79.2% to 92.5%) and specificity of 88.9% (CI, 81.7% to 93.5%) in predicting neoplastic change. In the studies that compared histology prediction performance before versus after CADx assistance (4 studies; 2503 polyps), there was no difference in the proportion of polyps predicted to be nonneoplastic that would avoid removal (55.4% vs. 58.4%; risk ratio [RR], 1.06 [CI, 0.96 to 1.17]; moderate-certainty evidence) or in the proportion of neoplastic polyps that would be erroneously left in situ (8.2% vs. 7.5%; RR, 0.95 [CI, 0.69 to 1.33]; moderate-certainty evidence). LIMITATION: The application of optical diagnosis was only simulated, potentially altering the decision-making process of the operator. CONCLUSION: Computer-aided diagnosis provided no incremental benefit or harm in the management of small rectosigmoid polyps during colonoscopy. PRIMARY FUNDING SOURCE: European Commission. (PROSPERO: CRD42023402197).

Newborn and child health national and provincial clinical practice guidelines in South Africa, Nigeria and Malawi: a scoping review.

BACKGROUND: Low and middle-income countries remain disproportionately affected by high rates of child mortality. Clinical practice guidelines are essential clinical tools supporting implementation of effective, safe, and cost-effective healthcare. High-quality evidence-based guidelines play a key role in improving clinical management to impact child mortality. We aimed to identify and assess the quality of guidelines for newborn and child health published in South Africa, Nigeria and Malawi in the last 5 years (2017-2022). METHODS: We searched relevant websites (June-July 2022), for publicly available national and subnational de novo or adapted guidelines, addressing newborn and child health in the three countries. Pairs of reviewers independently extracted information from eligible guidelines (scope, topic, target population and users, responsible developers, stakeholder consultation process, adaptation description, assessment of evidence certainty). We appraised guideline quality using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument. RESULTS: We identified 40-guidelines from the three countries. Of these, 8/40 reported being adopted from a parent guideline. More guidelines (n = 19) provided guidance on communicable diseases than on non-communicable diseases (n = 8). Guidelines were most often developed by national health ministries (n = 30) and professional societies (n = 14). Eighteen guidelines reported on stakeholder consultation; with Nigeria (10/11) and Malawi (3/6) faring better than South Africa (5/23) in reporting this activity. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used in 1/7 guidelines that reported assessing certainty of evidence. Overall guidelines scored well on two AGREE II domains: scope and purpose median (IQR) score 68% (IQR 47-83), and clarity of presentation 81% (67-94). Domains critical for ensuring credible guidance scored below 20%: rigour of development 11% (4-32) and editorial independence 6% (0-27). CONCLUSION: National ministries and professional societies drive guideline activities in Malawi, Nigeria and South Arica. However, the methods and reporting do not adhere to global standards. We found low AGREE II scores for rigour of guideline development and editorial independence and limited use of GRADE or adaptation methods. This undermines the credibility of available guidelines to support evidence-informed care. Our findings highlight the importance of ongoing efforts to strengthen partnerships, capacity, and support for guideline development.

Real-Time Computer-Aided Detection of Colorectal Neoplasia During Colonoscopy : A Systematic Review and Meta-analysis.

BACKGROUND: Artificial intelligence computer-aided detection (CADe) of colorectal neoplasia during colonoscopy may increase adenoma detection rates (ADRs) and reduce adenoma miss rates, but it may increase overdiagnosis and overtreatment of nonneoplastic polyps. PURPOSE: To quantify the benefits and harms of CADe in randomized trials. DESIGN: Systematic review and meta-analysis. (PROSPERO: CRD42022293181). DATA SOURCES: Medline, Embase, and Scopus databases through February 2023. STUDY SELECTION: Randomized trials comparing CADe-assisted with standard colonoscopy for polyp and cancer detection. DATA EXTRACTION: Adenoma detection rate (proportion of patients with ≥1 adenoma), number of adenomas detected per colonoscopy, advanced adenoma (≥10 mm with high-grade dysplasia and villous histology), number of serrated lesions per colonoscopy, and adenoma miss rate were extracted as benefit outcomes. Number of polypectomies for nonneoplastic lesions and withdrawal time were extracted as harm outcomes. For each outcome, studies were pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. DATA SYNTHESIS: Twenty-one randomized trials on 18 232 patients were included. The ADR was higher in the CADe group than in the standard colonoscopy group (44.0% vs. 35.9%; relative risk, 1.24 [95% CI, 1.16 to 1.33]; low-certainty evidence), corresponding to a 55% (risk ratio, 0.45 [CI, 0.35 to 0.58]) relative reduction in miss rate (moderate-certainty evidence). More nonneoplastic polyps were removed in the CADe than the standard group (0.52 vs. 0.34 per colonoscopy; mean difference [MD], 0.18 polypectomy [CI, 0.11 to 0.26 polypectomy]; low-certainty evidence). Mean inspection time increased only marginally with CADe (MD, 0.47 minute [CI, 0.23 to 0.72 minute]; moderate-certainty evidence). LIMITATIONS: This review focused on surrogates of patient-important outcomes. Most patients, however, may consider cancer incidence and cancer-related mortality important outcomes. The effect of CADe on such patient-important outcomes remains unclear. CONCLUSION: The use of CADe for polyp detection during colonoscopy results in increased detection of adenomas but not advanced adenomas and in higher rates of unnecessary removal of nonneoplastic polyps. PRIMARY FUNDING SOURCE: European Commission Horizon 2020 Marie Sklodowska-Curie Individual Fellowship.

Evaluating the impact of the global evidence, local adaptation (GELA) project for enhancing evidence-informed guideline recommendations for newborn and young child health in three African countries: a mixed-methods protocol.

BACKGROUND: Poverty-related diseases (PRD) remain amongst the leading causes of death in children under-5 years in sub-Saharan Africa (SSA). Clinical practice guidelines (CPGs) based on the best available evidence are key to strengthening health systems and helping to enhance equitable health access for children under five. However, the CPG development process is complex and resource-intensive, with substantial scope for improving the process in SSA, which is the goal of the Global Evidence, Local Adaptation (GELA) project. The impact of research on PRD will be maximized through enhancing researchers and decision makers' capacity to use global research to develop locally relevant CPGs in the field of newborn and child health. The project will be implemented in three SSA countries, Malawi, South Africa and Nigeria, over a 3-year period. This research protocol is for the monitoring and evaluation work package of the project. The aim of this work package is to monitor the various GELA project activities and evaluate the influence these may have on evidence-informed decision-making and guideline adaptation capacities and processes. The specific project activities we will monitor include (1) our ongoing engagement with local stakeholders, (2) their capacity needs and development, (3) their understanding and use of evidence from reviews of qualitative research and, (4) their overall views and experiences of the project. METHODS: We will use a longitudinal, mixed-methods study design, informed by an overarching project Theory of Change. A series of interconnected qualitative and quantitative data collections methods will be used, including knowledge translation tracking sheets and case studies, capacity assessment online surveys, user testing and in-depth interviews, and non-participant observations of project activities. Participants will comprise of project staff, members of the CPG panels and steering committees in Malawi, South Africa and Nigeria, as well as other local stakeholders in these three African countries. DISCUSSION: Ongoing monitoring and evaluation will help ensure the relationship between researchers and stakeholders is supported from the project start. This can facilitate achievement of common goals and enable researchers in South Africa, Malawi and Nigeria to make adjustments to project activities to maximize stakeholder engagement and research utilization. Ethical approval has been provided by South African Medical Research Council Human Research Ethics Committee (EC015-7/2022); The College of Medicine Research and Ethics Committee, Malawi (P.07/22/3687); National Health Research Ethics Committee of Nigeria (01/01/2007).

Using a priority setting exercise to identify priorities for guidelines on newborn and child health in South Africa, Malawi, and Nigeria.

BACKGROUND: Sub-Saharan Africa is the region with the highest under-five mortality rate globally. Child healthcare decisions should be based on rigorously developed evidence-informed guidelines. The Global Evidence, Local Adaptation (GELA) project is enhancing capacity to use global research to develop locally relevant guidelines for newborn and child health in South Africa (SA), Malawi, and Nigeria. The first step in this process was to identify national priorities for newborn and child health guideline development, and this paper describes our approach. METHODS: We followed a good practice method for priority setting, including stakeholder engagement, online priority setting surveys and consensus meetings, conducted separately in South Africa, Malawi and Nigeria. We established national Steering Groups (SG), comprising 10-13 members representing government, academia, and other stakeholders, identified through existing contacts and references, who helped prioritise initial topics identified by research teams and oversaw the process. Various stakeholders were consulted via online surveys to rate the importance of topics, with results informing consensus meetings with SGs where final priority topics were agreed. RESULTS: Based on survey results, nine, 10 and 11 topics were identified in SA, Malawi, and Nigeria respectively, which informed consensus meetings. Through voting and discussion within meetings, and further engagement after the meetings, the top three priority topics were identified in each country. In SA, the topics concerned anemia prevention in infants and young children and post-discharge support for caregivers of preterm and LBW babies. In Malawi, they focused on enteral nutrition in critically ill children, diagnosis of childhood cancers in the community, and caring for neonates. In Nigeria, the topics focused on identifying pre-eclampsia in the community, hand hygiene compliance to prevent infections, and enteral nutrition for LBW and preterm infants. CONCLUSIONS: Through dynamic and iterative stakeholder engagement, we identified three priority topics for guideline development on newborn and child health in SA, Malawi and Nigeria. Topics were specific to contexts, with no overlap, which highlights the importance of contextualised priority setting as well as of the relationships with key decisionmakers who help define the priorities.

Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·41, 95% CI -12·54 to -10·27). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop.

In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need.

Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure : A Systematic Review and Meta-analysis.

BACKGROUND: Randomized controlled trials established the cardiac protection of sodium-glucose cotransporter-2 (SGLT2) inhibitors among adults with type 2 diabetes. New evidence suggests that these results could extend to people without diabetes. PURPOSE: To evaluate the effect of SGLT2 inhibitors in patients with heart failure, regardless of the presence of type 2 diabetes. DATA SOURCES: PubMed, Web of Science, Cochrane Library, and Embase (OVID interface). STUDY SELECTION: Eligible trials randomly assigned adults with heart failure to SGLT2 inhibitors or control. DATA EXTRACTION: Time-to-event individual patient data were reconstructed from published Kaplan-Meier plots; time-varying risk ratios (RRs) were calculated in half-, 1-, and 2-year time frames; and anticipated absolute benefits were calculated using simple models applying relative effects to baseline risks. DATA SYNTHESIS: Sodium-glucose cotransporter-2 inhibitors reduce hospitalization for heart failure by 37% (95% CI, 25% to 47%) at 6 months, 32% (CI, 20% to 42%) at 1 year, and 26% (CI, 10% to 40%) at 2 years (all high certainty) and reduce cardiovascular death by 14% (CI, 1% to 25%) at 1 year (high certainty). Nevertheless, low-certainty evidence did not indicate protection against all-cause death, kidney disease progression, or kidney failure. Anticipated absolute benefits are greater for patients treated in the first year and for those with poorer prognoses, such as those newly diagnosed with heart failure in the hospital. In addition, SGLT2 inhibitors doubled the risk for genital infections (RR, 2.69 [CI, 1.61 to 4.52]; high certainty). LIMITATION: Covariates were unavailable in meta-analyses with reconstructed individual patient data. CONCLUSION: Among people with heart failure, SGLT2 inhibitors reduce hospitalizations for heart failure regardless of the presence of diabetes; absolute benefits are most pronounced in first-year treatment and vary with prognostic factors. Clinicians should note the increased risk for genital infection in patients receiving SGLT2 inhibitors. PRIMARY FUNDING SOURCE: 1.3.5 Project for Disciplines of Excellence, West China Hospital of Sichuan University. (PROSPERO: CRD42021255544).

A Reporting Tool for Adapted Guidelines in Health Care: The RIGHT-Ad@pt Checklist.

BACKGROUND: Adaptation of existing guidelines can be an efficient way to develop contextualized recommendations. Transparent reporting of the adaptation approach can support the transparency and usability of the adapted guidelines. OBJECTIVE: To develop an extension of the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement for the reporting of adapted guidelines (including recommendations that have been adopted, adapted, or developed de novo), the RIGHT-Ad@pt checklist. DESIGN: A multistep process was followed to develop the checklist: establishing a working group, generating an initial checklist, optimizing the checklist (through an initial assessment of adapted guidelines, semistructured interviews, a Delphi consensus survey, an external review, and a final assessment of adapted guidelines), and approval of the final checklist by the working group. SETTING: International collaboration. PARTICIPANTS: A total of 119 professionals participated in the development process. MEASUREMENTS: Participants' consensus on items in the checklist. RESULTS: The RIGHT-Ad@pt checklist contains 34 items grouped in 7 sections: basic information (7 items); scope (6 items); rigor of development (10 items); recommendations (4 items); external review and quality assurance (2 items); funding, declaration, and management of interest (2 items); and other information (3 items). A user guide with explanations and real-world examples for each item was developed to provide a better user experience. LIMITATION: The RIGHT-Ad@pt checklist requires further validation in real-life use. CONCLUSION: The RIGHT-Ad@pt checklist has been developed to improve the reporting of adapted guidelines, focusing on the standardization, rigor, and transparency of the process and the clarity and explicitness of adapted recommendations. PRIMARY FUNDING SOURCE: None.

Chronic fatigue syndromes: real illnesses that people can recover from.

The 'Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

Report from the CVOT Summit 2021: new cardiovascular, renal, and glycemic outcomes.

The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18-19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year's focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1-5, and STEP 1-5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed.Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10-11, 2022 ( http://www.cvot.org ).

UEG and EAES rapid guideline: Systematic review, meta-analysis, GRADE assessment and evidence-informed European recommendations on TaTME for rectal cancer.

BACKGROUND: Evidence and practice recommendations on the use of transanal total mesorectal excision (TaTME) for rectal cancer are conflicting. OBJECTIVE: We aimed to summarize best evidence and develop a rapid guideline using transparent, trustworthy, and standardized methodology. METHODS: We developed a rapid guideline in accordance with GRADE, G-I-N, and AGREE II standards. The steering group consisted of general surgeons, members of the EAES Research Committee/Guidelines Subcommittee with expertise and experience in guideline development, advanced medical statistics and evidence synthesis, biostatisticians, and a guideline methodologist. The guideline panel consisted of four general surgeons practicing colorectal surgery, a radiologist with expertise in rectal cancer, a radiation oncologist, a pathologist, and a patient representative. We conducted a systematic review and the results of evidence synthesis by means of meta-analyses were summarized in evidence tables. Recommendations were authored and published through an online authoring and publication platform (MAGICapp), with the guideline panel making use of an evidence-to-decision framework and a Delphi process to arrive at consensus. RESULTS: This rapid guideline provides a weak recommendation for the use of TaTME over laparoscopic or robotic TME for low rectal cancer when expertise is available. Furthermore, it details evidence gaps to be addressed by future research and discusses policy considerations. The guideline, with recommendations, evidence summaries, and decision aids in user-friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/4494 . CONCLUSIONS: This rapid guideline provides evidence-informed trustworthy recommendations on the use of TaTME for rectal cancer.

EAES rapid guideline: systematic review, network meta-analysis, CINeMA and GRADE assessment, and European consensus on bariatric surgery-extension 2022.

BACKGROUND: The European Association for Endoscopic Surgery Bariatric Guidelines Group identified a gap in bariatric surgery recommendations with a structured, contextualized consideration of multiple bariatric interventions. OBJECTIVE: To provide evidence-informed, transparent and trustworthy recommendations on the use of sleeve gastrectomy, Roux-en-Y gastric bypass, adjustable gastric banding, gastric plication, biliopancreatic diversion with duodenal switch, one anastomosis gastric bypass, and single anastomosis duodeno-ileal bypass with sleeve gastrectomy in patients with severe obesity and metabolic diseases. Only laparoscopic procedures in adults were considered. METHODS: A European interdisciplinary panel including general surgeons, obesity physicians, anesthetists, a psychologist and a patient representative informed outcome importance and minimal important differences. We conducted a systematic review and frequentist fixed and random-effects network meta-analysis of randomized-controlled trials (RCTs) using the graph theory approach for each outcome. We calculated the odds ratio or the (standardized) mean differences with 95% confidence intervals for binary and continuous outcomes, respectively. We assessed the certainty of evidence using the CINeMA and GRADE methodologies. We considered the risk/benefit outcomes within a GRADE evidence to decision framework to arrive at recommendations, which were validated through an anonymous Delphi process of the panel. RESULTS: We identified 43 records reporting on 24 RCTs. Most network information surrounded sleeve gastrectomy and Roux-en-Y gastric bypass. Under consideration of the certainty of the evidence and evidence to decision parameters, we suggest sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass over adjustable gastric banding, biliopancreatic diversion with duodenal switch and gastric plication for the management of severe obesity and associated metabolic diseases. One anastomosis gastric bypass and single anastomosis duodeno-ileal bypass with sleeve gastrectomy are suggested as alternatives, although evidence on benefits and harms, and specific selection criteria is limited compared to sleeve gastrectomy and Roux-en-Y gastric bypass. The guideline, with recommendations, evidence summaries and decision aids in user friendly formats can also be accessed in MAGICapp:  https://app.magicapp.org/#/guideline/Lpv2kE CONCLUSIONS: This rapid guideline provides evidence-informed, pertinent recommendations on the use of bariatric and metabolic surgery for the management of severe obesity and metabolic diseases. The guideline replaces relevant recommendations published in the EAES Bariatric Guidelines 2020.

EAES rapid guideline: appendicitis in the elderly.

BACKGROUND: There is a lack of trustworthy evidence-informed guidelines on the diagnosis and management of acute appendicitis in elderly patients. METHODS: We developed a rapid guideline in accordance with GRADE and AGREE II standards. The steering group consisted of general surgeons, members of the EAES Research Committee/Guidelines Subcommittee with expertise and experience in guideline development, advanced medical statistics and evidence synthesis, biostatisticians, and a guideline methodologist. The guideline panel consisted of three general surgeons, an intensive care physician, a geriatrician and a patient advocate. We conducted systematic reviews and the results of evidence synthesis were summarized in evidence tables. Recommendations were authored and published through an online authoring and publication platform (MAGICapp), with the guideline panel making use of an evidence-to-decision framework and a Delphi process to arrive at consensus. RESULTS: This rapid guideline provides a weak recommendation against the use of clinical scoring systems to replace cross-sectional imaging in the diagnostic approach of suspected appendicitis in elderly patients. It provides a weak recommendation against the use of antibiotics alone over surgical treatment in patients who are deemed fit for surgery, and a weak recommendation for laparoscopic over open surgery. Furthermore, it provides a summary of surgery-associated risks in elderly patients. The guidelines, with recommendations, evidence summaries and decision aids in user-friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/4494 . CONCLUSIONS: This rapid guideline provides evidence-informed trustworthy recommendations on the diagnosis and management of acute appendicitis in elderly patients.

Decision aids linked to evidence summaries and clinical practice guidelines: results from user-testing in clinical encounters.

BACKGROUND: Tools for shared decision-making (e.g. decision aids) are intended to support health care professionals and patients engaged in clinical encounters involving shared decision-making. However, decision aids are hard to produce, and onerous to update. Consequently, they often do not reflect best current evidence, and show limited uptake in practice. In response, we initiated the Sharing Evidence to Inform Treatment decisions (SHARE-IT) project. Our goal was to develop and refine a new generation of decision aids that are generically produced along digitally structured guidelines and evidence summaries. METHODS: Applying principles of human-centred design and following the International Patient Decision Aid Standards (IPDAS) and GRADE methods for trustworthy evidence summaries we developed a decision aid prototype in collaboration with the Developing and Evaluating Communication strategies to support Informed Decisions and practice based on Evidence project (DECIDE). We iteratively user-tested the prototype in clinical consultations between clinicians and patients. Semi-structured interviews of participating clinicians and patients were conducted. Qualitative content analysis of both user-testing sessions and interviews was performed and results categorized according to a revised Morville's framework of user-experience. We made it possible to produce, publish and use these decision aids in an electronic guideline authoring and publication platform (MAGICapp). RESULTS: Direct observations and analysis of user-testing of 28 clinical consultations between physicians and patients informed four major iterations that addressed readability, understandability, usability and ways to cope with information overload. Participants reported that the tool supported natural flow of the conversation and induced a positive shift in consultation habits towards shared decision-making. We integrated the functionality of SHARE-IT decision aids in MAGICapp, which has since generated numerous decision aids. CONCLUSION: Our study provides a proof of concept that encounter decision aids can be generically produced from GRADE evidence summaries and clinical guidelines. Online authoring and publication platforms can help scale up production including continuous updating of electronic encounter decision aids, fully integrated with evidence summaries and clinical practice guidelines.

Subacromial decompression surgery for adults with shoulder pain: a systematic review with meta-analysis.

OBJECTIVE: To determine the benefits and harms of subacromial decompression surgery in adult patients with subacromial pain syndrome lasting for more than 3 months. DESIGN: Systematic review with meta-analysis. MAIN OUTCOME MEASURES: Pain, physical function and health-related quality of life. DATA SOURCES: Systematic searches for benefits and harms were conducted to 23 July 2018 in MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Database of Abstracts of Reviews of Effects, and Health Technology Assessment. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing subacromial decompression surgery for subacromial pain syndrome with any other treatment(s). For harms, we included prospective cohort studies. REVIEW METHODS: Two reviewers independently determined eligibility, extracted the data and assessed the risk of bias of eligible studies. Thirty patients seeking primary or outpatient care for subacromial pain syndrome and a parallel guideline committee (BMJ Rapid Recommendations) provided input regarding systematic review design and interpretation. RESULTS: There was high certainty evidence of no additional benefit of subacromial decompression surgery over placebo surgery in reducing pain at 1 year following surgery (mean difference [MD] -0.26, 95% CI -0.84 to 0.33, minimally important difference [MID] 1.5) or improving physical function at 1-2 years (MD 2.8, 95% CI -1.4 to 6.9, MID 8.3). There was moderate certainty evidence for no additional benefit of subacromial decompression surgery on health-related quality of life at 1 year (MD -0.03 points, 95% CI -0.11 to 0.06, MID 0.07). There was moderate certainty evidence for six serious harms per 1000 (95% CI 5 to 7) patients undergoing subacromial decompression. CONCLUSION: Subacromial decompression surgery provided no important benefit compared with placebo surgery or exercise therapy, and probably carries a small risk of serious harms. SYSTEMATIC REVIEWREGISTRATION NUMBER: CRD42018086862.

Effects of dietary and physical activity interventions on the risk of type 2 diabetes in South Asians: meta-analysis of individual participant data from randomised controlled trials.

AIMS/HYPOTHESIS: Individuals of South Asian origin have a high risk of type 2 diabetes and of dying from a diabetes-attributable cause. Lifestyle modification intervention trials to prevent type 2 diabetes in high-risk South Asian adults have suggested more modest effects than in European-origin populations. The strength of the evidence of individual studies is limited, however. We performed an individual participant data meta-analysis of available RCTs to assess the effectiveness of lifestyle modification in South Asian populations worldwide. METHODS: We searched PubMed, EMBASE, Cochrane Library and Web of Science (to 24 September 2018) for RCTs on lifestyle modification interventions incorporating diet and/or physical activity in South Asian adults. Reviewers identified eligible studies and assessed the quality of the evidence. We obtained individual participant data on 1816 participants from all six eligible trials (four from Europe and two from India). We generated HR estimates for incident diabetes (primary outcome) and mean differences for fasting glucose, 2 h glucose, weight and waist circumference (secondary outcomes) using mixed-effect meta-analysis overall and by pre-specified subgroups. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence of the estimates. The study is registered with the International Prospective Register of Systematic Reviews ([PROSPERO] CRD42017078003). RESULTS: Incident diabetes was observed in 12.6% of participants in the intervention groups and in 20.0% of participants in the control groups. The pooled HR for diabetes incidence was 0.65 (95% CI 0.51, 0.81; I2 = 0%) in intervention compared with control groups. The absolute risk reduction was 7.4% (95% CI 4.0, 10.2), with no interactions for the pre-specified subgroups (sex, BMI, age, study duration and region where studies were performed). The quality of evidence was rated as moderate. Mean difference for lifestyle modification vs control groups for 2 h glucose was -0.34 mmol/l (95% CI -0.62, -0.07; I2 = 50%); for weight -0.75 kg (95% CI -1.34, -0.17; I2 = 71%) and for waist -1.16 cm (95% CI -2.16, -0.16; I2 = 75%). No effect was found for fasting glucose. Findings were similar across subgroups, except for weight for European vs Indian studies (-1.10 kg vs -0.08 kg, p = 0.02 for interaction). CONCLUSIONS/INTERPRETATION: Despite modest changes for adiposity, lifestyle modification interventions in high-risk South Asian populations resulted in a clinically important 35% relative reduction in diabetes incidence, consistent across subgroups. If implemented on a large scale, lifestyle modification interventions in high-risk South Asian populations in Europe would reduce the incidence of diabetes in these populations.