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Background: Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization. This may result in complications, the most serious of which is Clostridium difficile–associated diarrhea (CDAD).Purpose: To assess the efficacy and safety of probiotics for the prevention of CDAD in adults and children receiving antibiotics.Data Sources: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, Web of Science, and 12 gray-literature sources.Study Selection: Randomized, controlled trials including adult or pediatric patients receiving antibiotics that compared any strain or dose of a specified probiotic with placebo or with no treatment control and reported the incidence of CDAD.Data Extraction: Two reviewers independently screened potentially eligible articles; extracted data on populations, interventions, and outcomes; and assessed risk of bias. The Grading of Recommendations Assessment, Development and Evaluation guidelines were used to independently rate overall confidence in effect estimates for each outcome.Data Synthesis: Twenty trials including 3818 participants met the eligibility criteria. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I(2) = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I(2) = 17%).Limitations: In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data.Conclusion: Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

AIM: This paper is a report of a study conducted to describe people's experiences, and meanings of these, while living with irritable bowel syndrome. BACKGROUND: Irritable bowel syndrome is characterized by abdominal pain, diarrhoea and/or constipation, distension and bloating. Such symptoms are stigmatized in western societies. Patients may experience negative attitudes from healthcare personnel, and they can feel helpless and frustrated trying to control symptoms. METHOD: A qualitative, hermeneutic approach was used. Open-ended interviews were conducted during 2005-2006 with 13 patients currently diagnosed with irritable bowel syndrome. The interview setting was a rural healthcare centre or the person's home. An interpretive analysis of the data was performed. FINDINGS: Four interwoven themes were identified in the data: Living with unpredictability, represented by the subthemes 'not being in control', 'not being able to trust' and 'invasion of privacy'; preserving dignity, described by 'living with sacrifice', 'taking command' and 'fulfilling obligations'; 'reconciling struggle'; and 'living with comorbidity'. CONCLUSION: The unpredictability and taboos of irritable bowel syndrome made these people suffer, feel constrained and dependent. Dignity was preserved both by sacrifices and taking command. Healthcare personnel should allow patients to talk about their suffering and discomfort to decrease their experience of suffering. Our study contributes to a more nuanced understanding of life with this unpleasant companion, the suffering it creates and the threats to dignity and health. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The study evaluates the prevalence and diagnoses of abdominal complaints in general practice, and compares characteristics and symptoms of patients with functional gastrointestinal disorders (FGIDs) and organic diseases. DESIGN: A cross-sectional study. SETTING: Nine centres with 26 participating general practitioners (GPs) in Norway. SUBJECTS: 3097 out of 3369 consecutive adult patients answered a questionnaire regarding abdominal complaints IN the last 3 months. Those who consulted for the complaints were eligible for this study. MAIN OUTCOME MEASURES: The GPs' diagnoses and patients' characteristics were reported in questionnaires. RESULTS: 460 out of 1499 patients with abdominal complaints consulted for these complaints; 392 were included in this study. The GPs diagnosed an FGID in 167 (42.6%) patients, organic disease in 145 (37.0%), and made no diagnosis in 80 (20.4%). Stress-related symptoms were a statistically significant predictor of a FGID (OR 1.95) and weight loss predicted in addition organic disease (OR 2.7) in 128 patients with a verified diagnosis. CONCLUSION: Abdominal complaints are a common problem in general practice. The distinction between FGID, which accounted for half of the diagnoses, and organic disease was difficult. The only significant predictor for FGID was stress-related symptoms. [ABSTRACT FROM AUTHOR]

Background: This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies.Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.Results: We present 23 recommendations for pertinent clinical questions. For primary prevention of cardiovascular disease, we suggest low-dose aspirin (75-100 mg/d) in patients aged > 50 years over no aspirin therapy (Grade 2B). For patients with established coronary artery disease, defined as patients 1-year post-acute coronary syndrome, with prior revascularization, coronary stenoses > 50% by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing, we recommend long-term low-dose aspirin or clopidogrel (75 mg/d) (Grade 1A). For patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI) with stent placement, we recommend for the first year dual antiplatelet therapy with low-dose aspirin in combination with ticagrelor 90 mg bid, clopidogrel 75 mg/d, or prasugrel 10 mg/d over single antiplatelet therapy (Grade 1B). For patients undergoing elective PCI with stent placement, we recommend aspirin (75-325 mg/d) and clopidogrel for a minimum duration of 1 month (bare-metal stents) or 3 to 6 months (drug-eluting stents) (Grade 1A). We suggest continuing low-dose aspirin plus clopidogrel for 12 months for all stents (Grade 2C). Thereafter, we recommend single antiplatelet therapy over continuation of dual antiplatelet therapy (Grade 1B).Conclusions: Recommendations continue to favor single antiplatelet therapy for patients with established coronary artery disease. For patients with acute coronary syndromes or undergoing elective PCI with stent placement, dual antiplatelet therapy for up to 1 year is warranted. [ABSTRACT FROM AUTHOR]

Background: The use of anticoagulant therapy during pregnancy is challenging because of the potential for both fetal and maternal complications. This guideline focuses on the management of VTE and thrombophilia as well as the use of antithrombotic agents during pregnancy.Methods: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.Results: We recommend low-molecular-weight heparin for the prevention and treatment of VTE in pregnant women instead of unfractionated heparin (Grade 1B). For pregnant women with acute VTE, we suggest that anticoagulants be continued for at least 6 weeks postpartum (for a minimum duration of therapy of 3 months) compared with shorter durations of treatment (Grade 2C). For women who fulfill the laboratory criteria for antiphospholipid antibody (APLA) syndrome and meet the clinical APLA criteria based on a history of three or more pregnancy losses, we recommend antepartum administration of prophylactic or intermediate-dose unfractionated heparin or prophylactic low-molecular-weight heparin combined with low-dose aspirin (75-100 mg/d) over no treatment (Grade 1B). For women with inherited thrombophilia and a history of pregnancy complications, we suggest not to use antithrombotic prophylaxis (Grade 2C). For women with two or more miscarriages but without APLA or thrombophilia, we recommend against antithrombotic prophylaxis (Grade 1B).Conclusions: Most recommendations in this guideline are based on observational studies and extrapolation from other populations. There is an urgent need for appropriately designed studies in this population. [ABSTRACT FROM AUTHOR]

Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA).Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence.Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B).Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. [ABSTRACT FROM AUTHOR]

Background: Development of clinical practice guidelines involves making trade-offs between desirable and undesirable consequences of alternative management strategies. Although the relative value of health states to patients should provide the basis for these trade-offs, few guidelines have systematically summarized the relevant evidence. We conducted a systematic review relating to values and preferences of patients considering antithrombotic therapy.Methods: We included studies examining patient preferences for alternative approaches to antithrombotic prophylaxis and studies that examined, in the context of antithrombotic prophylaxis or treatment, how patients value alternative health states and experiences with treatment. We conducted a systematic search and compiled structured summaries of the results. Steps in the process that involved judgment were conducted in duplicate.Results: We identified 48 eligible studies. Sixteen dealt with atrial fibrillation, five with VTE, four with stroke or myocardial infarction prophylaxis, six with thrombolysis in acute stroke or myocardial infarction, and 17 with burden of antithrombotic treatment.Conclusion: Patient values and preferences regarding thromboprophylaxis treatment appear to be highly variable. Participant responses may depend on their prior experience with the treatments or health outcomes considered as well as on the methods used for preference elicitation. It should be standard for clinical practice guidelines to conduct systematic reviews of patient values and preferences in the specific content area. [ABSTRACT FROM AUTHOR]

Background: High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices.Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.Results: Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education.Conclusions: We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied. [ABSTRACT FROM AUTHOR]

Background: To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists.Methods: Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion.Results: One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance.Conclusions: AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review. [ABSTRACT FROM AUTHOR]

Clinical Question: What is the comparative effectiveness and safety of commonly used interventional procedures (such as spinal injections and ablation procedures) for chronic axial and radicular spine pain that is not associated with cancer or inflammatory arthropathy?, Current Practice: Chronic spine pain is a common, potentially disabling complaint, for which clinicians often administer interventional procedures. However, clinical practice guidelines provide inconsistent recommendations for their use., Recommendations: For people living with chronic axial spine pain (≥3 months), the guideline panel issued strong recommendations against: joint radiofrequency ablation with or without joint targeted injection of local anaesthetic plus steroid; epidural injection of local anaesthetic, steroids, or their combination; joint-targeted injection of local anaesthetic, steroids, or their combination; and intramuscular injection of local anaesthetic with or without steroids. For people living with chronic radicular spine pain (≥3 months), the guideline panel issued strong recommendations against: dorsal root ganglion radiofrequency with or without epidural injection of local anaesthetic or local anaesthetic plus steroids; and epidural injection of local anaesthetic, steroids, or their combination., How This Guideline Was Created: An international guideline development panel including four people living with chronic spine pain, 10 clinicians with experience managing chronic spine pain, and eight methodologists, produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation provided methodological support. The guideline panel applied an individual patient perspective when formulating recommendations., The Evidence: These recommendations are informed by a linked systematic review and network meta-analysis of randomised trials and a systematic review of observational studies, summarising the current body of evidence for benefits and harms of common interventional procedures for axial and radicular, chronic, non-cancer spine pain. Specifically, injection of local anaesthetic, steroids, or their combination into the cervical or lumbar facet joint or sacroiliac joint; epidural injections of local anaesthetic, steroids, or their combination; radiofrequency of dorsal root ganglion; radiofrequency denervation of cervical or lumbar facet joints or the sacroiliac joint; and paravertebral intramuscular injections of local anaesthetic, steroids, or their combination., Understanding the Recommendations: These recommendations apply to people living with chronic spine pain (≥3 months duration) that is not associated with cancer or inflammatory arthropathy and do not apply to the management of acute spine pain. Further research is warranted and may alter recommendations in the future: in particular, whether there are differences in treatment effects based on subtypes of chronic spine pain, establishing the effectiveness of interventional procedures currently supported by low or very low certainty evidence, and effects on poorly reported patient-important outcomes (such as opioid use, return to work, and sleep quality)., Competing Interests: Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/sites/default/files/attachments/resources/2016/03/16-current-bmj-education-coi-form.pdf., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Recent clinical practice guidelines for diabetes, obesity, cardiovascular disease (CVD) and chronic kidney disease (CKD) emphasise a holistic, person-centred approach to care. However, they do not include recommendations for the assessment of patient-reported outcomes (PROs), which would - dependent on the topic of guideline - be important for improving shared decision-making, patients' concordance with guideline recommendations, clinical outcomes and health-related quality of life (HRQoL). The Taskforce of the Guideline Workshop discussed PROs in diabetes, obesity, CVD and CKD as well as the relevance of their inclusion in clinical practice guidelines for the management of these conditions., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Katharine Barnard-Kelly is founder and shareholder at Spotlight-AQ Ltd. KBK has received research support from Dexcom, Embecta, JDRF, Novo Nordisk and Roche Diabetes Care, and honoraria from Sanofi. Tadej Battelino has served on the advisory boards of Abbott, Boehringer Ingelheim, Dreamed Diabetes, Eli Lilly and Company, Indigo Diabetes, Medtronic, Novo Nordisk, and Sanofi. TB has received speaker’s bureau honoraria from Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche, and Sanofi. The University Medical Center has received research grant support from Abbott, GluSense, Medtronic, Novo Nordisk, Sandoz, Sanofi, and Zealand Pharma. Frank C. Brosius is a consultant for MAKSCIENTIFIC. Antonio Ceriello reports consulting and speaking for Bayer, Berlin-Chemie, Eli Lilly and Company, Guidotti, Merck, Novo Nordisk, Roche Diagnostics and Sanofi. Francesco Cosentino has nothing reported. Julian Elliott has nothing reported. James R. Gavin III has served on the advisory boards of Abbott Diabetes Care and Embecta, and on the speaker’s bureaus of Boehringer Ingelheim and Eli Lilly and Company. Francesco Giorgino has served on the advisory boards of AstraZeneca, Eli Lilly and Company, Novo Nordisk, Roche Diabetes Care, Sanofi and as a consultant to AstraZeneca, Boehringer Ingelheim, LifeScan, Medimmune, Medtronic, Merck Sharp & Dohme, Roche Diabetes Care and Sanofi. FG has also received research support from Eli Lilly and Company and Roche Diabetes Care. Jennifer Green has nothing reported. Linong Ji declares that he has no competing interests. Monika Kellerer has served on advisory boards of Abbott Diabetes Care, Astra Zeneca, Bayer AG, Boehringer-Ingelheim, Eli Lilly, NovoNordisk and Sanofi. Sue Koob has nothing reported. Mikhail Kosiborod reports consulting or advisory board participation for 35Pharma, Alnylam Pharmaceuticals, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly and Company, Esperion Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, scPharmaceuticals, Sanofi, Structure Therapeutics, Vifor Pharma and Youngene Therapeutics. MK has also received honoraria from AstraZeneca, Boehringer Ingelheim and Novo Nordisk, and research grants from AstraZeneca, Boehringer Ingelheim and Pfizer. Nebojsa Lalic declares that he has no competing interests. Nikolaus Marx has received research grants from Boehringer Ingelheim and MSD, speaking fees form Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Eli Lilly and Company, MSD, Novo Nordisk, and Sanofi-Aventis and has served or serves on the advisory board of Amgen, Bayer, BMS, Boehringer Ingelheim, MSD, Novo Nordisk, and Sanofi-Aventis. Prashant Nedungadi has nothing reported. Christopher G. Parkin has nothing reported. Helena W. Rodbard declares that she has no competing interests. René D. Rötzer is employee of Sciarc GmbH. Lars Rydén declares that he has no competing interests related to this work. Wayne Sheu has nothing reported. Eberhard Standl declares that he has no competing interests. Britta Tendal Jeppesen declares that she has no competing interests. Pinar Topsever has received honoraria or consulting fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, and LifeScan, and has served on the speaker’s bureau for AstraZeneca. PT received grant/research support from PCDE, made possible by corporate sponsorship from AstraZeneca, Eli Lilly, Novo Nordisk, and Roche Diagnostics; the sponsors had no input into the study protocols. Per Olav Vandvik has nothing reported. Christoph Wanner received honoraria for steering committee and adboard participation as well as lecturing from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, MSD, Novo Nordisk and Sanofi. Oliver Schnell is founder and CEO at Sciarc GmbH, Baierbrunn, Germany., (© 2025. The Author(s).)

Background: The resect-and-discard strategy allows endoscopists to replace post-polypectomy pathology with real-time prediction of polyp histology during colonoscopy (optical diagnosis). We aimed to investigate the benefits and harms of implementing computer-aided diagnosis (CADx) for polyp pathology into the resect-and-discard strategy., Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Scopus from database inception to June 5, 2024, without language restrictions, for diagnostic accuracy studies that assessed the performance of real-time CADx systems, compared with histology, for the optical diagnosis of diminutive polyps (≤5 mm) in the entire colon. We synthesised data for three strategies: CADx-alone, CADx-unassisted, and CADx-assisted; when the endoscopist was involved in the optical diagnosis, we synthesised data exclusively from diagnoses for which confidence in the prediction was reported as high. The primary outcomes were the proportion of polyps that would have avoided pathological assessment (ie, the proportion optically diagnosed with high confidence; main benefit) and the proportion of polyps incorrectly predicted due to false positives and false negatives (main harm), directly compared between CADx-assisted and CADx-unassisted strategies. We used DerSimonian and Laird's random-effects model to calculate all outcomes. We used Higgins I 2 to assess heterogeneity, the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate certainty, and funnel plots and Egger's test to examine publication bias. This study is registered with PROSPERO, CRD42024508440., Findings: We found 1019 studies, of which 11 (7400 diminutive polyps, 3769 patients, and 185 endoscopists) were included in the final meta-analysis. Three studies (1817 patients and 4086 polyps [2148 neoplastic and 1938 non-neoplastic]) provided data to directly compare the primary outcome measures between the CADx-unassisted and CADx-assisted strategies. We found no significant difference between the CADx-assisted and CADx-unassisted strategies for the proportion of polyps that would have avoided pathological assessment (90% [88-93], 3653 [89·4%] of 4086 polyps diagnosed with high confidence vs 90% [95% CI 85-94], 3588 [87·8%] of 4086 polyps diagnosed with high confidence; risk ratio 1·01 [95% CI 0·99-1·04; I 2 =53·49%; low-certainty evidence; Egger's test p=0·18). The proportion of incorrectly predicted polyps was lower with the CADx-assisted strategy than with the CADx-unassisted strategy (12% [95% CI 7-17], 523 [14·3%] of 3653 polyps incorrectly predicted with a CADx-assisted strategy vs 13% [6-20], 582 [16·2%] of 3588 polyps incorrectly diagnosed with a CADx-unassisted strategy; risk ratio 0·88 [95% CI 0·79-0·98]; I 2 =0·00%; low-certainty evidence; Egger's test p=0·18)., Interpretation: CADx did not produce benefit nor harm for the resect-and-discard strategy, questioning its value in clinical practice. Improving the accuracy and explainability of CADx is desired., Funding: European Commission (Horizon Europe), the Japan Society of Promotion of Science, and Associazione Italiana per la Ricerca sul Cancro., Competing Interests: Declaration of interests CHas reports consultancy fees from Fujifilm and Medtronic. YM reports consultancy fees, speaking honoraria, and equipment loan from Olympus, and license fee for the co-developed artificial intelligence medical devices from Cybernet System (in the field of colonoscopy, one of which has been included in the analysis in this Article). AR reports consultancy fees from Fujifilm, Olympus, and Medtronic. DvR reports research grants from Fujifilm, Eberhard & Robert Bosch Elektronik (ERBE), and Boston Scientific; speaker fees from Fujifilm, ERBE, Boston Scientific, and Medtronic; support for attending meetings from Fujifilm and ERBE, and endoscopy device loan from Fujifilm and ERBE. ER reports speaking honoraria from Fujifilm; consultancy fees from Medtronic; and speaker fees from Fujifilm. OP reports speaker fees from Medtronic, Boston Scientific, AbbVie, Falk, Luvos, and Olympus. ED reports consulting fees from Olympus, Fujifilm, Ambu, InterVenn, Norgine, and Exact Science; speaker fees from Olympus, GI Supply, Norgine, IPSEN-Mayoly, and Fujifilm; and endoscopy device loan from Fujifilm. POV reports research grant from European Comission (Horizon Europe 101057099). PS reports research grants from ERBE, Fujifilm, Nippon Electric Company, and Sebela; and consulting fees from Olympus, Boston Scientific, Salix Pharmaceuticals, Cipla, Medtronic, Takeda, Samsung Bioepis, and CDx. DKR reports research grants from Olympus, Sebela Pharmaceuticals, and ERBE; consulting fees from Olympus, Sebela Pharmaceuticals, Boston Scientific, and Laborie Medical; speaker fees from Boston Scientific, Laborie Medical, and Medtronic; and ownership of stock in Satisfai Health. PB reports research grants from NEC-Europe, Boston Scientific, and 3-D matrix and consulting fees from Fujifilm. GA reports research grants from the European Society of Gastrointestinal Endoscopy, consulting fees from Medtronic and Cosmo IMD, and speaker fees from Medtronic. JWL reports speaker fees from Olympus and Fujifilm. MMe reports license fee for the co-developed artificial intelligence medical devices from Cybernet System (in the field of colonoscopy, one of which has been included in the analysis in this Article) and consulting fees and speaker fees from Olympus. S-eK reports license fees for the co-developed artificial intelligence medical devices from Cybernet System (in the field of colonoscopy, one of which has been included in the analysis in this Article) and speaker fees from Olympus. RM reports research grants from ERBE, Fujifilm, Olympus, Pentax, and Boston Scientific. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Clinical Question: In adult patients with inflammatory bowel disease, inflammatory arthritis (rheumatoid arthritis, spondyloarthritis, psoriatic arthritis), or psoriasis taking biologic drugs, does proactive therapeutic drug monitoring (TDM) improve outcomes as compared with standard care?, Context and Current Practice: Standard care for immune mediated inflammatory diseases includes prescribing biologic drugs at pre-determined doses. Dosing may be adjusted reactively, for example with increased disease activity. In proactive TDM, serum drug levels and anti-drug antibodies are measured irrespective of disease activity, and the drug dosing is adjusted to achieve target serum drug levels, usually within pre-specified therapeutic ranges. The role of proactive TDM in clinical practice remains unclear, with conflicting guideline recommendations and emerging evidence from randomised controlled trials., The Evidence: Linked systematic review and pairwise meta-analysis which identified 10 trials including 2383 participants. Inflammatory bowel disease, inflammatory arthritis, and psoriasis were grouped together as best current research evidence on proactive TDM did not suggest heterogeneity of effects on outcomes of interest. Proactive TDM of intravenous infliximab during maintenance treatment may increase the proportion of patients who experience sustained disease control or sustained remission without considerable additional harm. For adalimumab, it remains unclear if proactive TDM during maintenance treatment has an effect on sustained disease control or sustained remission. At induction (start) of treatment, proactive TDM of intravenous infliximab may have little or no effect on achieving remission. No eligible trial evidence was available for proactive TDM of adalimumab at induction (start) of treatment. No eligible trial evidence was available for proactive TDM of other biologic drugs in maintenance or at induction (start) of treatment., Recommendations: The guideline panel issued the following recommendations for patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis:1. A weak recommendation in favour of proactive TDM for intravenous infliximab during maintenance treatment2. A weak recommendation against proactive TDM for adalimumab and other biologic drugs during maintenance treatment3. A weak recommendation against proactive TDM for intravenous infliximab, adalimumab, and other biologic drugs during induction (start) of treatment., Understanding the Recommendations: When considering proactive TDM, clinicians and patients should engage in shared decision making to ensure patients make choices that reflect their values and preferences. The availability of laboratory assays to implement proactive TDM should also be considered. Further research is warranted and may alter recommendations in the future., How This Guideline Was Created: An international panel including patient partners, clinicians, and methodologists produced these recommendations based on a linked systematic review and pairwise meta-analysis which identified 10 trials including 2383 participants. The panel followed standards for trustworthy guidelines and used the GRADE approach, explicitly considering the balance of benefits and harms and burdens of treatment from an individual patient perspective., Competing Interests: Competing interests: All authors have completed the BMJ Rapid Recommendations interest of disclosure form. MAGIC and The BMJ judged that no panel member or co-chair had any financial conflict of interest. Professional and academic interests are minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions. MAGIC and TheBMJ assessed declared interests from other coauthors of this publication and found no relevant conflicts of interests., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Clinical Question: What is the impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on survival and on cardiovascular and kidneyoutcomes for adults living with chronic kidney disease (CKD)?, Current Practice: Few therapies slow kidney disease progression and improve long term prognosis for adults living with CKD. SGLT-2 inhibitors have demonstrated cardiovascular and kidney benefits in adults with CKD with and without type 2 diabetes. Existing guidance for SGLT-2 inhibitors does not account for the totality of current best evidence for adults with CKD and does not provide fully stratified treatment effects and recommendations across all risk groups based on risk of CKD progression and complications., Recommendations: The guideline panel considered evidence regarding benefits and harms of SGLT-2 inhibitor therapy for adults with CKD over a five year period, along with contextual factors, and provided the following recommendations:1. For adults at low risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)2. For adults at moderate risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)3. For adults at high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour)4. For adults at very high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour).Recommendations are applicable to all adults with CKD, irrespective of type 2 diabetes status., How This Guideline Was Created: An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified typical risk strata of adults with CKD (from low to very high risk of CKD progression and related complications) using the classification system developed by Kidney Disease Improving Global Outcomes (KDIGO), and applied an individual patient perspective in moving from evidence to recommendations. Effects of SGLT-2 inhibitors were interpreted in absolute terms applicable to different risk strata with varying baseline risks for outcomes of benefit over a five year period. The panel explicitly considered the balance of benefits, harms, and burdens of starting an SGLT-2 inhibitor, incorporating the values and preferences of adults with different risk profiles. Interactive evidence summaries and decision aids accompany multilayered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that allows reuse and adaptation., The Evidence: A linked systematic review and pairwise meta-analysis (13 trials including 29 614 participants) of benefits and harms associated with SGLT-2 inhibitors in adults with CKD with or without type 2 diabetes informed guidance. Among individuals at very high risk of CKD progression and complications, moderate to high certainty evidence shows SGLT-2 inhibitors (relative to placebo or standard care without SGLT-2 inhibitors) decrease all-cause and cardiovascular mortality, hospitalisation for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke. Among individuals at high risk, moderate to high certainty evidence shows SGLT-2 inhibitors result in similar benefits across outcomes except demonstrating little or no effect on hospitalisation for heart failure and kidney failure. Among individuals at moderate and low risk, moderate to high certainty evidence shows SGLT-2 inhibitors probably reduce all-cause mortality and non-fatal stroke, with little or no effect for other outcomes of benefit. Risk-stratified estimates were unavailable for outcomes of harm; the panel therefore considered absolute effects summarised across risk strata. SGLT-2 inhibitors are associated with little or no effect on acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolaemia, although a residual possibility of harms at the individual patient level remains., Understanding the Recommendation: In order to apply recommendations, clinicians must appropriately identify adults with CKD, consider the underlying aetiology, and risk stratify them based on glomerular filtration rate (estimated or measured) and degree of albuminuria. In addition to classifying individuals into risk strata, further estimation of a given patient's risk based on the extent of their kidney disease and other comorbidities may be warranted to inform individual-level decisions and shared decision making. Available risk calculators may help estimate a given patient's risk of CKD progression and complications., Competing Interests: Competing interests: All authors have completed the BMJ Rapid Recommendations disclosure of interests form. The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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., Competing Interests: Declaration of competing interest T.A. reports a relationship with MAGIC Evidence Ecosystem Foundation that includes: board membership and employment. P.O.V. reports a relationship with MAGIC Evidence Ecosystem Foundation that includes: board membership and employment. P.O.V. and T.A. are CEO and deputy CEO of the nonprofit organization MAGIC Evidence Ecosystem Foundation (https://www.magicevidence.org). In collaboration with P.O.L. at Lovisenberg Diaconal Hospital, MAGIC is conducting the research project Making Alternative Treatment Choices Intuitive and Trustworthy (MATCH-IT). The overarching aim of MATCH-IT is to develop a new interactive SoF table and decision support tool, displaying multiple structured evidence summaries from NMAs. The tool may be integrated as part of MAGICapp (https://app.magicapp.org/#/guidelines), an online author and publication platform for guidelines, evidence summaries and decision aids. A.A.V. is Statistical Associate Editor for the Journal of Clinical Epidemiology, but had no involvement with the peer review process or decision for publication. A.C.T. is Coeditor-in-Chief for the Journal of Clinical Epidemiology, but had no involvement with the peer review process or decision for publication. X.W., T.P., M.Ø., and C.L. declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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)., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest T.A. is the Chair of the board and Deputy CEO of the nonprofit organization MAGIC Evidence Ecosystem Foundation (https://www.magicevidence.org). F.A. is a paid consultant for the MAGIC Evidence Ecosystem Foundation and is a part of the research team in MAGIC conducting the research project “Making Alternative Treatment Choices Intuitive and Trustworthy” (MATCH-IT). P.O.V is the CEO of the nonprofit organization MAGIC Evidence Ecosystem Foundation (https://www.magicevidence.org). P.O.L, B.S.H, and A.F.H are all part of the research team in MAGIC conducting the research project Making Alternative Treatment Choices Intuitive and Trustworthy (MATCH-IT). J.W.B. is partly supported by the Canadian Institutes of Health Research Canada Research Chair in the prevention and management of chronic pain. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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)., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2865.

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of interests SL received grants from the Sichuan Science and Technology Program (grant numbers 2019YFS0305 and 2019YFH0150). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024. The Author(s).)

Objectives: To investigate medical students' ability to interpret evidence, as well as their self-assessed understandability, perceived usefulness and preferences for design alternatives in an interactive decision support tool, displaying GRADE evidence summaries for multiple treatment options (Making Alternative Treatment CHoices Intuitive and Trustworthy, MATCH-IT)., Design: A combined randomised controlled trial and survey. Participants were presented with a clinical scenario and randomised to one of two versions of the MATCH-IT tool (A/B), instructed to explore the evidence and decide on a recommendation. Participants answered a questionnaire assessing interpretation, treatment recommendation self-assessed understandability and perceived usefulness before exposure to the other MATCH-IT version and asked questions on design preferences., Setting: Online lecture in an evidence-based medicine (EBM) introductory course., Participants: 149 third-year medical students. 52% (n=77) had 6 months of clinical training and 48% (n=72) had preclinical training only., Interventions: The MATCH-IT tool version A uses colour coding to categorise interventions by magnitude and direction of effects and displays all outcomes in a table on entry. Version B has no colour coding, and the user must decide which outcomes to display in the table., Main Outcome Measures: Interpretation of evidence, treatment recommendation, perceived usefulness and understandability, preference for format and design alternatives., Results: 82.5% (n=123) of medical students correctly answered ≥4 out of 5 multiple choice questions assessing interpretation of data. 75.8% (n=114) of students made a treatment recommendation in accordance with an expert panel for the same clinical scenario. 87.2% (n=130) found the tool understandable while 91.9% perceived the tool as useful in addressing the clinical scenario., Conclusion: Medical students with no prior training in EBM can interpret and use the MATCH-IT tool. Certain design alternatives were preferred but had no bearing on interpretation of evidence or understandability of the tool., Competing Interests: Competing interests: BSH and POL perform research on the MATCH-IT tool, within the MAGIC Evidence Ecosystem Foundation (MAGIC/ www.magicevidence.org). POV is the CEO of MAGIC and main supervisor for researchers within MATCH-IT. He may have intellectual conflicts of interests related to this research., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)