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.

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.

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).

A systematic survey of 200 systematic reviews with network meta-analysis (published 2020-2021) reveals that few reviews report structured evidence summaries.

OBJECTIVES: To map whether and how systematic reviews (SRs) with network meta-analysis (NMA) use presentation formats to report (a) structured evidence summaries - here defined as reporting of effects estimates in absolute effects with certainty ratings and with a method to rate interventions across one or more outcome(s) - and (b) NMA results in general. STUDY DESIGN AND SETTING: We conducted a systematic survey, searching MEDLINE (Ovid) for SRs with NMA published between January 1, 2020, and December 31, 2021. We planned to include a random sample of publications, with predefined mechanisms in place for saturation, and included SRs that met prespecified quality criteria and extracted data on presentation formats that reported: (a) estimates of effects, (b) certainty of the evidence, or (c) rating of interventions. RESULTS: The 200 eligible SRs, from 158 unique Journals, utilized 1133 presentation formats. We found structured evidence summaries in 10 publications (5.0%), with 3 (1.5%) reporting structured evidence summaries across all outcomes, including benefits and harms. Sixteen of the 133 SRs (11.7%) reporting dichotomous outcomes included estimates of absolute effects. Seventy-six SRs (38.0%) reported both benefits and harms and 26 SRs (13.0%) reported certainty ratings in presentation formats, 20 (76.9%) used Grading of Recommendations Assessment, Development and Evaluation and 6 (23.1%) used Confidence In Network Meta-analysis. Surface Under the Cumulative Ranking Curve was the most common method to rate interventions (69 SRs, 34.5%). NMA results were most often reported using forest plots (108 SRs, 54.0%) and league tables (93 SRs, 46.5%). CONCLUSION: Most SRs with NMA do not report structured evidence summaries and only rarely do such summaries include reporting of both benefits and harms; those that do offer effective user-friendly communication and provide models for optimal NMA presentation practice.

Open-door policy versus treatment-as-usual in urban psychiatric inpatient wards: a pragmatic, randomised controlled, non-inferiority trial in Norway.

BACKGROUND: Open-door policy is a recommended framework to reduce coercion in psychiatric wards. However, existing observational data might not fully capture potential increases in harm and use of coercion associated with open-door policies. In this first randomised controlled trial, we compared coercive practices in open-door policy and treatment-as-usual wards in an urban hospital setting. We hypothesised that the open-door policy would be non-inferior to treatment-as-usual on the proportion of patients exposed to coercive measures. METHODS: We conducted a pragmatic, randomised controlled, non-inferiority trial comparing two open-door policy wards and three treatment-as-usual acute psychiatric wards at Lovisenberg Diaconal Hospital in Oslo, Norway. An exemption from the consent requirements enabled inclusion and random allocation of all patients admitted to these wards using an open list (2:3 ratio) administrated by a team of ward nurses. The primary outcome was the proportion of patient stays with one or more coercive measures, including involuntary medication, isolation or seclusion, and physical and mechanical restraints. The non-inferiority margin was set to 15%. Primary and safety analyses were assessed using the intention-to-treat population. The trial is registered with ISRCTN registry and is complete, ISRCTN16876467. FINDINGS: Between Feb 10, 2021, and Feb 1, 2022, we randomly assigned 556 patients to either open-door policy wards (n=245; mean age 41·6 [SD 14·5] years; 119 [49%] male; 126 [51%] female; and 180 [73%] admitted to the ward involuntarily) or treatment-as-usual wards (n=311; mean age 41·6 [4·3] years; 172 [55%] male and 138 [45%] female; 233 [75%] admitted involuntarily). Data on race and ethnicity were not collected. The open-door policy was non-inferior to treatment-as-usual on all outcomes: the proportion of patient stays with exposure to coercion was 65 (26·5%) in open-door policy wards and 104 (33·4%) in treatment-as-usual wards (risk difference 6·9%; 95% CI -0·7 to 14·5), with a similar trend for specific measures of coercion. Reported incidents of violence against staff were 0·15 per patient stay in open-door policy wards and 0·18 in treatment-as-usual wards. There were no suicides during the randomised controlled trial period. INTERPRETATION: The open-door policy could be safely implemented without increased use of coercive measures. Our findings underscore the need for more reliable and relevant randomised trials to investigate how a complex intervention, such as open-door policy, can be efficiently implemented across health-care systems and contexts. FUNDING: South-Eastern Norway Regional Health Authority and The Research Council of Norway.

Physicians found an interactive tool displaying structured evidence summaries for multiple comparisons understandable and useful: a qualitative user testing study.

OBJECTIVES: To evaluate and improve "Making Alternative Treatment Choices Intuitive and Trustworthy" (MATCH-IT)-a digital, interactive decision support tool displaying structured evidence summaries for multiple comparisons-to help physicians interpret and apply evidence from network meta-analysis (NMA) for their clinical decision-making. STUDY DESIGN AND SETTING: We conducted a qualitative user testing study, applying principles from user-centered design in an iterative development process. We recruited a convenience sample of practicing physicians in Norway, Belgium, and Canada, and asked them to interpret structured evidence summaries for multiple comparisons-linked to clinical guideline recommendations-displayed in MATCH-IT. User testing included (a) introduction of a clinical scenario, (b) a think-aloud session with participant-tool interaction, and (c) a semistructured interview. We video recorded, transcribed, and analyzed user tests using directed content analysis. The results informed new updates in MATCH-IT. RESULTS: Distributed across 5 development cycles we tested MATCH-IT with 26 physicians. Of these, 24 (94%) reported either no or sparse prior experience with interpretation of NMA. Physicians perceived MATCH-IT as easy to interpret and navigate, and appreciated its ability to provide an overview of the evidence. Visualization of effects in pictograms and inclusion of information on burden of treatment ("practical issues") were highlighted as potentially useful features in interacting with patients. We also identified problems, including undiscovered functionalities (drag and drop), suboptimal tutorial, and cumbersome navigation of the tool. In addition, physicians wanted definition/explanation of key terms (eg, outcomes and "certainty"), and there were concerns that overwhelming evidence from a large NMA would complicate applicability to clinical practice. This led to several updates with development of a new start page, tutorial, updated user interface for more efficient maneuvering, solutions to display definition of key terms and a "frequently asked questions" section. To facilitate interpretation of large networks, we improved categorization of results using color coding and added filtering functionality. These modifications allowed physicians to focus on interventions of interest and reduce information overload. CONCLUSION: This study provides proof of concept that physicians can use MATCH-IT to understand NMA evidence. Key features of MATCH-IT in a clinical context include providing an overview of the evidence, visualization of effects, and the display of information on burden of treatments. However, unfamiliarity with the Grading of Recommendations Assessment, Development and Evaluation concepts, time constraints, and accessibility at the point of care may be challenges for use. To what extent our results are transferable to real-world clinical contexts remains to be explored.