OBJECTIVE: To summarize the literature on pharmacotherapy for managing paediatric obesity.
METHODS: A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) with <18-year-olds of pharmacotherapeutic agents published up to November 2022. Estimates of effect for outcomes were presented relative to minimal important differences and GRADE certainty of evidence. We examined data on patient/proxy-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry and adverse events (AEs).
RESULTS: Overall, 35 RCTs were included. Trials examined metformin (n = 26), glucagon-like peptide-1 receptor agonists (GLP1RAs) (n = 7) and a lipase inhibitor (orlistat; n = 2). Intervention duration varied (3-24 months). Metformin had little to no benefit on PROMs (e.g., health-related quality of life [HRQoL]; 6 RCTs), moderate reductions in triglycerides, a moderate decline in insulin resistance, a small to moderate decline in BMI z-score (BMIz) and a moderate increase in mild to moderate gastrointestinal AEs. Response to GLP1RAs was heterogeneous and results of subgroup analysis demonstrated variability of impact. Liraglutide (2 RCTs) resulted in a small reduction in HOMA-IR and BMIz, but little to no benefit on other outcomes. Exenatide (4 RCTs) had a moderate reduction on blood pressure and a small decrease in BMIz with little to no benefit on other outcomes. Semaglutide (1 RCT) had a small benefit on HRQoL, a small reduction on SBP, a moderate reduction on total cholesterol and LDL-cholesterol, a large reduction on triglyceride, and a very large decline in BMIz accompanied by a small increase in mild to moderate gastrointestinal AEs. Orlistat had a moderate reduction in DBP and little to no benefit in other outcomes measured, but had a very large increased risk of mild to moderate gastrointestinal AEs. Serious AEs were rare and for interventions with sufficent AE reporting, were considered not likely attributable to the interventions.
CONCLUSIONS: Few studies examined the impact of pharmacotherapy on PROMs. There is evidence that metformin and GLP1RAs lead to important improvements in cardiometabolic and anthropometric outcomes while accompanied by mild to moderate AEs. Long-term effectiveness and safety of GLP1RAs remain to be evaluated.

OBJECTIVE: Guidelines help physicians to provide optimal care for stroke patients, but implementation is challenging due to the quantity of recommendations. Therefore a practical overview related to applicability of recommendations can be of assistance.
METHODS: A systematic review was performed on ischaemic stroke guidelines published in scientific journals, covering the whole acute care process for patients with ischaemic stroke. After data extraction, experts rated the recommendations on dimensions of applicability, that is, actionability, feasibility and validity, on a 9-point Likert scale. Agreement was defined as a score of ≥8 by ≥80% of the experts.
RESULTS: Eighteen articles were identified and 48 recommendations were ultimately extracted. Papers were included only if they described the whole acute care process for patients with ischaemic stroke. Data extraction and analysis revealed variation in terms of both content and comprehensiveness of this description. Experts reached agreement on 34 of 48 (70.8%) recommendations in the dimension actionability, for 16 (33.3%) in feasibility and for 15 (31.3%) in validity. Agreement on all three dimensions was reached for seven (14.6%) recommendations: use of a stroke unit, exclusion of intracerebral haemorrhage as differential diagnosis, administration of intravenous thrombolysis, performance of electrocardiography/cardiac evaluation, non-invasive vascular examination, deep venous thrombosis prophylaxis and administration of statins if needed.
CONCLUSIONS: Substantial variation in agreement was revealed on the three dimensions of the applicability of recommendations. This overview can guide stroke physicians in improving the care process and removing barriers where implementation may be hampered by validity and feasibility.

The Japanese Society of Mood Disorders (JSMD) published treatment guidelines of bipolar disorder in 2011. The present guidelines incorporating new findings were developed to comply to the guidelines of the National Academy of Medicine (NAM) by utilizing systematic reviews and meta-analysis and taking patient and family opinions as well as insights from multiple professional fields into account. They support combination therapy using mood stabilizers and second-generation antipsychotics in many aspects. They also have limitations, including the grouping of mood stabilizers and second-generation antipsychotics when meta-analysis was performed despite their distinct properties, due to the scarcity of drug-specific evidence. Despite the limitations, these guidelines provide clinical decision support for psychiatrists in Japan.

The management of acute myocarditis (AM) is addressed in multiple clinical guidelines. We systematically reviewed current guidelines developed by national and international medical organizations on the management of AM to aid clinical practice. Publications in MEDLINE, EMBASE and Cochrane were identified between 1 January 2013 and 12 April 2024. Additionally, the websites of relevant organizations and the Guidelines International Network, Guideline Central, and NHS knowledge and library hub were reviewed. Two reviewers independently screened titles and abstracts, two reviewers assessed the rigour of guideline development, and one reviewer extracted the recommendations. Two of the three guidelines identified showed good rigour of development. Those rigorously developed agreed on the definition of AM, sampling serum troponin as part of the workflow for AM, testing for B-type natriuretic peptides in heart failure, key diagnostic imaging in the form of cardiovascular magnetic resonance, coronary angiography to exclude significant coronary disease, indications for endomyocardial biopsy (EMB), and indications for immunosuppression and advanced treatment options. Discrepancies exist in sampling creatine kinase-myocardial bound as a marker of myocardial injury, indications for EMB, and indications for immunosuppression and treatment of uncomplicated AM. Evidence is lacking for the use of 18F-Fluorodeoxyglucose Positron Emission Tomography for myocardial imaging, exercise restriction, follow-up measures and genetic testing, and there are few high-quality randomized trials to support treatment recommendations. Recommendations for management of AM in the guidelines have largely been developed from expert opinion rather than trial data.

BACKGROUND: The optimal mode of delivery for vaginal breech presentation remains a clinical dilemma. Planned vaginal delivery offers maternal advantages because it avoids major abdominal surgery and has no consequences for following pregnancies, while elective cesarean delivery proves advantageous for the neonate because adverse outcomes are less frequent. Patient selection for vaginal breech delivery is important based on the individual risk balance. A lack of consensus exists regarding the specific contraindications for vaginal breech delivery, largely due to limited scientific evidence. This systematic review aims to give an overview of contraindications for vaginal breech delivery, as presented in guidelines, analyze relevant literature, and offer evidence-based recommendations for the contraindications stated in the guidelines.
METHODS: To identify national guidelines PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, NICE, UpToDate, and ClinicalKey were searched using two keywords: \"breech presentation\" and \"vaginal delivery.\" We systematically reviewed the literature for existing evidence for contraindications for term vaginal breech delivery. The following databases were searched: PubMed (April 2024), the Cochrane Central Register of Controlled Trials, and EMBASE (1947 to 2024).
RESULTS: Our search identified eight guidelines that stated a total of 11 contraindications for vaginal breech delivery. Among these guidelines, agreement was limited, with the sole consensus in all guidelines on the contraindication of footling breech. Our comprehensive literature search yielded 43 articles discussing 14 potential contraindications. We found supportive evidence for 7 of 11 contraindications from the guidelines, with only substantial and satisfactory evidence for two contraindications.
CONCLUSIONS: The findings of this study underscore the lack of consensus among national guidelines regarding contraindications for term vaginal breech delivery. Furthermore, we found a notable lack of substantial scientific evidence to support these contraindications. In light of these findings, we suggest a reduced list of contraindications in vaginal breech deliveries.

BACKGROUND: The uptake of guidelines in care is inconsistent. This review focuses on guideline implementation strategies used by guideline organizations (governmental agencies, scientific/professional societies and other umbrella organizations), experienced implementation barriers and facilitators and impact of their implementation efforts.
METHODS: We searched PUBMED, EMBASE and CINAHL and conducted snowballing. Eligibility criteria included guidelines focused on hospital care and OECD countries. Study quality was assessed using the Mixed Methods Appraisal Tool. We used framework analysis, narrative synthesis and summary statistics.
RESULTS: Twenty-six articles were included. Sixty-two implementation strategies were reported, used in different combinations and ranged between 1 and 16 strategies per initiative. Most frequently reported strategies were educational session(s) and implementation supporting materials. The most commonly reported barrier and facilitator were respectively insufficient healthcare professionals\' time and resources; and guideline\'s credibility, evidence base and relevance. Eighty-five percent of initiatives that measured impact achieved improvements in adoption, knowledge, behavior and/or clinical outcomes. No clear optimal approach for improving guideline uptake and impact was found. However, we found indications that employing multiple active implementation strategies and involving external organizations and hospital staff were associated with improvements.
CONCLUSIONS: Guideline organizations employ diverse implementation strategies and encounter multiple barriers and facilitators. Our study uncovered potential effective implementation practices. However, further research is needed on effective tailoring of implementation approaches to increase uptake and impact of guidelines.

In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.

Neurovascular coupling (NVC) is the perturbation of cerebral blood flow (CBF) to meet varying metabolic demands induced by various levels of neural activity. NVC may be assessed by Transcranial Doppler ultrasonography (TCD), using task activation protocols, but with significant methodological heterogeneity between studies, hindering cross-study comparisons. Therefore, this review aimed to summarise and compare available methods for TCD-based healthy NVC assessments. Medline (Ovid), Scopus, Web of Science, EMBASE (Ovid) and CINAHL were searched using a predefined search strategy (PROSPERO: CRD42019153228), generating 6006 articles. Included studies contained TCD-based assessments of NVC in healthy adults. Study quality was assessed using a checklist, and findings were synthesised narratively. 76 studies (2697 participants) met the review criteria. There was significant heterogeneity in the participant position used (e.g., seated vs supine), in TCD equipment, and vessel insonated (e.g. middle, posterior, and anterior cerebral arteries). Larger, more significant, TCD-based NVC responses typically included a seated position, baseline durations >one-minute, extraneous light control, and implementation of previously validated protocols. In addition, complementary, combined position, vessel insonated and stimulation type protocols were associated with more significant NVC results. Recommendations are detailed here, but further investigation is required in patient populations, for further optimisation of TCD-based NVC assessments.

BACKGROUND: The implementation of clinical practice guidelines (CPGs) is a cyclical process in which the evaluation stage can facilitate continuous improvement. Implementation science has utilized theoretical approaches, such as models and frameworks, to understand and address this process. This article aims to provide a comprehensive overview of the models and frameworks used to assess the implementation of CPGs.
METHODS: A systematic review was conducted following the Cochrane methodology, with adaptations to the \"selection process\" due to the unique nature of this review. The findings were reported following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines. Electronic databases were searched from their inception until May 15, 2023. A predetermined strategy and manual searches were conducted to identify relevant documents from health institutions worldwide. Eligible studies presented models and frameworks for assessing the implementation of CPGs. Information on the characteristics of the documents, the context in which the models were used (specific objectives, level of use, type of health service, target group), and the characteristics of each model or framework (name, domain evaluated, and model limitations) were extracted. The domains of the models were analyzed according to the key constructs: strategies, context, outcomes, fidelity, adaptation, sustainability, process, and intervention. A subgroup analysis was performed grouping models and frameworks according to their levels of use (clinical, organizational, and policy) and type of health service (community, ambulatorial, hospital, institutional). The JBI\'s critical appraisal tools were utilized by two independent researchers to assess the trustworthiness, relevance, and results of the included studies.
RESULTS: Database searches yielded 14,395 studies, of which 80 full texts were reviewed. Eight studies were included in the data analysis and four methodological guidelines were additionally included from the manual search. The risk of bias in the studies was considered non-critical for the results of this systematic review. A total of ten models/frameworks for assessing the implementation of CPGs were found. The level of use was mainly policy, the most common type of health service was institutional, and the major target group was professionals directly involved in clinical practice. The evaluated domains differed between the models and there were also differences in their conceptualization. All the models addressed the domain \"Context\", especially at the micro level (8/12), followed by the multilevel (7/12). The domains \"Outcome\" (9/12), \"Intervention\" (8/12), \"Strategies\" (7/12), and \"Process\" (5/12) were frequently addressed, while \"Sustainability\" was found only in one study, and \"Fidelity/Adaptation\" was not observed.
CONCLUSIONS: The use of models and frameworks for assessing the implementation of CPGs is still incipient. This systematic review may help stakeholders choose or adapt the most appropriate model or framework to assess CPGs implementation based on their specific health context.
BACKGROUND: PROSPERO (International Prospective Register of Systematic Reviews) registration number: CRD42022335884. Registered on June 7, 2022.

BACKGROUND: Clinical practice guidelines (CPGs) are a helpful tool for the evidence-based management of Type 2 Diabetes Mellitus (T2D). The aim of this systematic review was to synthesize and appraise the scope and quality of South Asian T2D CPGs.
METHODS: This PROPSERO registered (CRD42023425150) systematic review adhered to the 2020 PRISMA guidelines. We searched the PubMed, Embase, Cochrane, and Google Scholar databases for relevant guidelines. Data synthesis was performed using a qualitative approach and methodological quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool.
RESULTS: We identified eleven unique CPGs (three each from Pakistan and Sri Lanka, two from India, and one each from Bangladesh, Nepal, and Bhutan) which were published or updated between 2017 and 2023. The CPGs included recommendations regarding screening, diagnosis, prevention, and management of T2D and its acute and chronic complications, comorbidities, and fasting with T2D. The AGREE II mean domain scores ranged from 37 % to 80 %; three CPGs were \'recommended for clinical use,\' seven were \'recommended for use with modifications\' and one was deemed unfit for implementation.
CONCLUSIONS: The present review summarized and appraised broadly CPGs from South Asia for T2D and can help direct improvements to future iterations.