Prehabilitation in Patients Undergoing Cardiac Procedures: A Systematic Review and Meta-Analysis.

Delirium is frequent in critically ill patients and is associated with increased mortality. Discrepancies were found in the results of recent randomized controlled trials (RCTs) regarding the effect of melatonin to prevent delirium onset in critically ill patients. We searched MEDLINE, Embase, and Web of Science from inception to 5 July 2025 for RCTs evaluating melatonin in critically ill patients. The primary outcome was the incidence of delirium. The main secondary outcome was mortality. We generated pooled risk ratios (RR). To base our conclusions on the highest quality of evidence, our primary analysis was based only on the trials with low to moderate risk of bias for each outcome. A secondary analysis was conducted, including all the trials. The study was registered with PROSPERO (CRD420251041661). Our primary analysis was based on six RCTs with 2209 patients and did not show any difference in the incidence of delirium attributable to the treatment with melatonin (RR 0.89, [95% confidence interval (CI) 0.73-1.09]). This result was consistent with the secondary analysis including thirteen RCTs with 2830 patients (RR 0.86, [95% CI 0.70-1.04]). No association was found between mortality and melatonin in the primary (seven RCTs, 2165 patients, RR 0.87, [95% CI 0.73-1.02]) and secondary (8 RCTs, 2396 patients, RR 0.92, [95% CI 0.79-1.06]) analyses. The results suggest that compared to placebo, melatonin does not reduce delirium incidence in critically ill patients. Similarly, no effect was observed on mortality.

Medical expulsive therapy (MET) has been a matter of debate for many years. A number of randomised controlled trials (RCTs) and meta-analyses have been conducted, but outcomes have been varied. This makes it challenging to determine the benefit of using MET as an adjunct in patients with expectantly managed ureteric stones. This article aimed to summarize both the historic and the more contemporary literature in this area by focusing on published meta-analyses and recent RCTs. Studies of interest were those comparing either an α-blocker or a calcium channel blocker with a control. Outcome measures of interest were expulsion rates, expulsion times, and medication-related side effects. All systematic reviews included are in favour of MET versus controls. However, many of the component RCTs had limitations such as a high risk of bias, incomplete blinding and heterogeneous inclusion criteria. A recent well-powered RCT found no benefit of MET for the purpose of conservatively managed ureteric stones. This study had some limitations that stimulated further research in the area, adding to the uncertainty. The most recent RCT and meta-analysis indicates MET is more beneficial in both larger (>5mm) and distal stones. Uncertainty remains in this arena, and there is a need for a robust multi-institution study to assess MET in a cohort of patients who are expectantly managed with ureteric stones. This should serve to counter the marked heterogeneity and limitations of existing trials and meta-analyses.

Pre-Emptive TIPS Versus Standard Care for Patients With Cirrhosis and Variceal Bleeding: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

STUDY QUESTIONDid weight reduction in obese women scheduled for IVF increase cumulative live birth rate (CLBR) after 2 years?SUMMARY ANSWERWeight loss prior to IVF did not increase CLBR.WHAT IS KNOWN ALREADYFew studies have investigated the effect of weight reduction in obese infertile women scheduled for IVF. In a recent randomized controlled trial (RCT), including one IVF cycle, we found no increase in live birth rate after weight reduction. Weight regain after obesity reduction treatment often occurs, and children born to obese women have a higher risk of childhood obesity.STUDY DESIGN, SIZE, DURATIONA 2-year follow-up of a multicenter, RCT running between 2012 and 2018 was performed. Out of 317 women randomized to weight reduction followed by IVF treatment or IVF treatment-only, 305 remained in the full analysis set. Of these women, 90.5% (276/305) participated in this study.PARTICIPANTS/MATERIALS, SETTING, METHODSNine infertility clinics in Sweden, Denmark and Iceland participated in the RCT. Obese women under 38 years of age having a BMI ≥30 and < 35 kg/m2 were randomized to weight reduction and IVF or IVF-only. In all, 160 patients were randomized to a low calorie diet for 12 weeks and 3–5 weeks of weight stabilization, before IVF and 157 patients to IVF-only. Two years after randomization, the patients filled in a questionnaire regarding current weight, live births and ongoing pregnancies.MAIN RESULTS AND THE ROLE OF CHANCE42 additional live births were achieved during the follow-up in the weight reduction and IVF group, and 40 additional live births in the IVF-only group, giving a CLBR, the main outcome of this study, of 57.2% (87/152) and 53.6% (82/153), respectively (P = 0.56; odds ratio (OR) 1.16, 95% CI: 0.74–1.52). Most of the women in the weight reduction and IVF group had regained their pre-study weight after 2 years. The mean weight gain over the 2 years was 8.6 kg, while women in the IVF-only group had a mean weight loss of 1.2 kg. At the 2-year follow-up, the weight standard deviation scores of the children born in the original RCT (index cycle) were 0.218 (1.329) (mean, SD) in the weight reduction and IVF group and − 0.055 (1.271) (mean, SD) in the IVF-only group (P = 0.25; mean difference between groups, 0.327; 95% CI: −0.272 to 0.932).LIMITATIONS, REASON FOR CAUTIONAll data presented in this follow-up study were self-reported by the participants, which could affect the results. A further limitation is in power for the main outcome. The study is a secondary analysis of a large RCT, where the original power calculation was based on live-birth rate after one cycle and not on CLBR.WIDER IMPLICATIONS OF THE FINDINGSThe follow-up indicates that for women with a BMI ≥30 and < 35 kg/m2 and scheduled for IVF, the weight reduction did not increase their chance of a live birth either in the index cycle or after 2 years. It also shows that even in this highly motivated group, a regain of pre-study weight occurred.STUDY FUNDING/COMPETING INTEREST(S)The 2-year follow-up was financed by grants from the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-70940 and ALFGBG-77690), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Hjalmar Svensson Foundation. Ms Kluge has nothing to disclose. Dr Bergh has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Einarsson has been reimbursed for lectures for Merck and Ferring. Dr Thurin-Kjellberg reports grants from Merck, and reimbursement for lectures from Merck outside the submitted work. Dr Pinborg has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Englund has nothing to disclose.TRIAL REGISTRATION NUMBERClinicalTrials.gov number, NCT01566929.

Magnesium sulfate (MgSO4) is widely used in analgesia for different conditions. Recent randomized controlled trials (RCTs) have evaluated the effects of MgSO4 on renal colic; however, this new evidence has not been synthesized. Thus, we conducted a systematic review and meta-analysis to assess the efficacy and safety of MgSO4 in comparison with control for renal colic. PubMed, EMBASE, and Scopus databases were searched from inception to February 2020. We included RCTs that evaluated MgSO4 vs control for patients with renal colic. Data were independently extracted by 2 reviewers and synthesized using a random-effects model. Four studies with a total of 373 patients were analyzed. Intravenous MgSO4 15 to 50 mg/kg did not significantly reduce renal colic pain severity at 15 minutes (mean difference [MD] = 0.35, 95% confidence interval [CI] -0.51 to 1.21; 2 RCTs), 30 minutes (MD = 0.19, 95% CI -0.74 to 1.13; 4 RCTs), and 60 minutes (MD = -0.28, 95% CI -0.72 to 0.16; 3 RCTs) in comparison with controls. In patients who failed to respond to initial analgesics, intravenous MgSO4 15 mg/kg or 2 ml of 50% solution provided similar pain relief to ketorolac or morphine at 30 minutes (P = .90) and 60 minutes (P = .57). No significant hemodynamic changes were observed with short-term use of MgSO4 in these studies. MgSO4 provides no superior therapeutic benefits in comparison with control treatments. MgSO4 may be used as a rescue medication in patients not responding to initial analgesics. The short-term use of MgSO4 did not affect hemodynamic values.

113 Background: The treatment landscape for M0 CRPC has changed following the demonstrated efficacy of new agents in recent randomized control trials (RCT). However, the comparative effectiveness of these novel agents is unknown. This NMA indirectly compared the efficacy and safety of available therapies for M0 CRPC. Methods: A literature search of MEDLINE (Ovid), EBM Reviews, HealthSTAR, PubMed, PubMed Central, CINAHL, and TRIP Database was performed. Studies were screened by two independent reviewers. Hazard ratios (HR) and confidence intervals were extracted for the primary outcome metastasis-free survival (MFS) and the secondary outcomes overall survival (OS) and grade 3 or higher adverse events (AE). Bone MFS was used as a surrogate for MFS when MFS was not reported. Risk of bias was assessed using the Cochrane Collaboration tool. A Bayesian NMA was performed using a fixed-effects model. Results: Four RCT were analyzed (n=5549). Each trial compared either apalutamide (APA), enzalutamide (ENZA), darolutamide (DARO), or denosumab (DENO) plus androgen deprivation therapy (ADT) to placebo plus ADT. Risk of bias was low. For MFS, APA and ENZA had similar efficacy (Table), and Surface Under the Cumulative Ranking Analysis demonstrated a 59% probability that APA was preferred for MFS, followed by ENZA (41%). There was a trend for improved OS for APA, DARO and ENZA, but no meaningful differences between these agents. APA, ENZA, and DARO had a similar risk of AEs and all had a greater risk of AEs compared to DENO. Conclusions: APA and ENZA appear to be the most efficacious treatments for MFS in M0 CRPC, though more data for OS is required. Compared to DARO, APA and ENZA’s demonstrated efficacy is not at the expense of added toxicity.[Table: see text]

ObjectivesThe predominant concern during pregnancy is musculoskeletal pain, often accompanied by additional discomforts such as anxiety and insomnia. Pilates, as a low-impact mind-body exercise, may be beneficial in managing musculoskeletal pain and associated symptoms in adults. This systematic review and meta-analysis aimed to synthesise the evidence on the effectiveness of Pilates for alleviating musculoskeletal pain and other discomforts during pregnancy.DesignSystematic review and meta-analysis.Data sourcesPubMed, Scopus, TRIP Medical Database, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to 14 January 2026.Eligibility criteriaRandomised controlled trials and prospective non-randomised controlled studies that compared Pilates with other prenatal care modalities for improving musculoskeletal pain and discomfort were eligible.Data extraction and synthesisTwo researchers independently extracted data using standardised forms with subsequent cross-verification. Risk of bias was assessed using the Cochrane Risk of Bias V.2.0 tool. Meta-analyses were performed using random-effects models. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach.Results13 studies were included in the systematic review, of which 10 contributed data to the meta-analysis. Primary outcomes were pain intensity and disability level. Pain intensity was assessed using Visual Analogue Scale (range 0–10). Moderate-certainty evidence demonstrated that Pilates significantly reduced musculoskeletal pain during pregnancy (mean differences (MD)=−2.59, 95% CI −4.19 to −1.00; I²=91%, p=0.001). Low-certainty evidence suggested that Pilates reduced pregnancy-related disability (standardised mean differences (SMD)=−1.82, 95% CI −2.99 to −0.66; I² = 93%, p=0.002). Secondary outcomes comprised sleep quality and psychological status. Multivariate meta-analysis showed significant improvements in psychological status (SMD=−0.86, 95% CI −1.31 to −0.42; τ²=0.4, I²=86%, p=0.0005) but did not yield statistically significant improvements in sleep quality (MD=−1.93, 95% CI −4.70 to 0.84; I²=93%, p=0.17). Both secondary outcomes were supported by very low-certainty evidence. Risk of bias assessment rated three studies as high risk, three as unclear risk and seven as low risk. Formal assessment of publication bias was not feasible owing to the limited number of studies (fewer than 10 per outcome).ConclusionThis meta-analysis demonstrates that, compared with standard care, structured prenatal Pilates significantly alleviates musculoskeletal pain and disability while also enhancing psychological status.PROSPERO registration numberCRD42024628027.

'Fast-track surgery' or 'enhanced recovery protocol' or 'fast-track rehabilitation', incorporating one or more elements of preoperative education, pain relief, early mobilisation, enteral nutrition and growth factors, may improve health-related quality of life and reduce length of hospital stay and costs. The role of enhanced recovery protocols in major upper gastrointestinal, liver and pancreatic surgery is unclear. To assess the benefits and harms of enhanced recovery protocols compared with standard care (or usual practice) in major upper gastrointestinal, liver and pancreatic surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library; 2015, Issue 3), MEDLINE, EMBASE and Science Citation Index Expanded until March 2015 to identify randomised trials. We also searched the references of included trials to identify further trials. We considered only randomised controlled trials (RCTs) performed in people undergoing major upper gastrointestinal, liver and pancreatic surgery, irrespective of language, blinding or publication status for inclusion in the review. Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CIs) using both fixed-effect and random-effects models using Review Manager 5, based on available case analysis. Ten studies met the inclusion criteria for the review, and nine studies provided information on one or more outcomes for the review. A total of 1014 participants were randomly assigned to the enhanced recovery protocol (499 participants) or standard care (515 participants) in the nine RCTs. Most of the trials included low anaesthetic risk participants with high performance status undergoing different upper gastrointestinal, liver and pancreatic surgeries. Eight trials incorporated more than one element of the enhanced recovery protocol. All of the trials were at high risk of bias. The overall quality of evidence was low or very low.None of the trials reported long-term mortality, medium-term health-related quality of life(three months to one year), time to return to normal activity, or time to return to work. The difference between the enhanced recovery protocol and standard care were imprecise for short-term mortality (enhanced recovery protocol: 4/425 (adjusted proportion = 0.6%); standard care: 1/443 (0.2%); seven trials; 868 participants; RR 2.79; 95% CI 0.44 to 17.73; very low quality evidence), proportion of people with serious adverse events (enhanced recovery protocol: 4/157 (adjusted proportion = 0.6%); standard care: 0/184 (0.0%); two trials; 341 participants; RR 5.57; 95% CI 0.68 to 45.89; very low quality evidence), number of serious adverse events (enhanced recovery protocol: 34/421 (8 per 100 participants); standard care: 46/438 (11 per 100 participants); seven trials; 859 participants; rate ratio 0.72; 95% CI 0.45 to 1.13; very low quality evidence), health-related quality of life (four trials; 373 participants; SMD 0.29; 95% CI -0.04 to 0.62; very low quality evidence) and hospital readmissions (enhanced recovery protocol: 14/355 (adjusted proportion = 3.3%); standard care: 9/378 (2.4%); seven trials; 733 participants; RR 1.4; 95% CI 0.69 to 2.87; very low quality evidence). The enhanced recovery protocol group had a lower proportion of people with mild adverse events (enhanced recovery protocol: 31/254 (adjusted proportion = 10.9%); standard care: 51/271 (18.8%); four trials; 525 participants; RR 0.58; 95% CI 0.39 to 0.85; low quality evidence), fewer number of mild adverse events (enhanced recovery protocol: 69/499 (13 per 100 participants); standard care: 128/515 (25 per 100 participants); nine trials; 1014 participants; rate ratio 0.52; 95% CI 0.39 to 0.70; low quality evidence), shorter length of hospital stay (nine trials; 1014 participants; MD -2.19 days; 95% CI -2.53 to -1.85; low quality evidence) and lower costs (four trials; 282 participants; MD USD -6300; 95% CI -8400 to -4200; low quality evidence) than standard care group. Based on low quality evidence, enhanced recovery protocols may reduce length of hospital stay and costs (primarily because of reduction in hospital stay) in people undergoing major upper gastrointestinal, liver and pancreatic surgeries. However, the validity of the results is uncertain because of the risk of bias in the trials and the way the outcomes were measured. Future RCTs should be conducted with low risk of bias, and measure clinically important outcomes for including the three months to one year period.

Introduction Obesity and diabetes are ongoing public health concerns in the United States, especially in rural communities. Obesity is a leading cause of many conditions such as cardiovascular diseases and diabetes. Diabetes, specifically Type 2 Diabetes Mellitus (T2DM), is a leading cause of many conditions such as heart disease and vision problems. Commercially available green tea (Camellia sinensis) products may promote weight loss and insulin sensitivity as indicated by change in Body Mass Index (BMI) and insulin-resistance markers, which could provide potential benefit in the adjunctive management of obesity and diabetes. We conducted a meta-analysis on recent randomized controlled trials (RCTs) to test the hypothesis that consumption of green tea (GT) or green tea extract (GTE) for over four weeks can lead to a decrease in BMI and/or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Our study results will provide updated guidance on dietary recommendations and offer insight into effect sizes translatable to the general population. Methods Electronic databases including PubMed were searched for parallel-designed and double-blinded RCTs published between 2010 and 2020 that examined the effect of GT and GTE on BMI and/or HOMA-IR Index. Two authors independently reviewed articles for inclusion with differences resolved by consensus. Three authors independently assessed studies to assign risk of bias scores. Heterogeneity of studies was evaluated through use of forest plots and the I2 statistic using RevMan5 software. When necessary, data of varying measurement units were synthesized by meta-analysis. Results Eleven studies involving over 800 subjects were included. Daily doses of green tea ranged from 379 mg standardized extract to 20 mg green tea solids. Duration of interventions ranged from 4 to 48 weeks. Preliminary analysis indicates a statistically significant (p<0.05) percentage change in BMI and HOMA-IR index with mean effect sizes of –2.29% (95% CI –4.45%, -0.13%, p=0.04) and –19.75% (95% CI -35.11%, -4.39%, p=0.01), respectively. Most included studies had unknown or high risk of bias. Conclusions Included studies were widely varied in patient selection, dosing, dosing strategy, and outcome measurements. However, these differences suggest broader applicability of the results. Adding green tea may be an accessible, inexpensive and well-tolerated dietary change that may reduce the risk of chronic diseases associated with obesity and diabetes. Future research opportunities include conducting large RCTs to address the public health concern of obesity, diabetes and preventive medicine.

People with schizophrenia often experience long-term psychosocial disabilities and frequent relapse. Family plays a key role in caring for ill relatives, which in turn probably contributes to high levels of distress and burdens for the family. Family-based interventions have been developed and applied to family members and their relatives with schizophrenia to improve their outcomes. This is an update of a Cochrane review that was last updated in 2011, which has been split into this review, one on group- versus individual-based family interventions and one on family-based cognitive versus behavioural management interventions. To assess the effects of family-based interventions for people with schizophrenia or schizophrenia-like disorders and their families compared with standard care. We searched the following electronic databases from inception until April 2023: CENTRAL, Medline, Embase, PsycInfo, CINAHL, WHO International Clinical Trials Registry Platform (ICTRP), Clinicaltrials.gov, SinoMed, China Network Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journals Database (VIP). We also searched the reference lists of included studies and accessible reviews for additional references. We included randomised controlled trials (RCTs) that compared the effects of family-based interventions for people with schizophrenia or schizophrenia-like disorders and their families and reported at least one patient's and one family member's outcomes. In this update, we only investigated standard care as the comparator. We used standard Cochrane methods. The review authors independently screened studies, extracted data, and assessed risk of bias for each study using the Cochrane risk of bias tool for RCTs. We pooled data and estimated effects with the mean difference (MD), standardised mean difference (SMD), or risk ratio (RR) with 95% confidence interval (CI). We judged the certainty of evidence using GRADEpro GDT. We divided the outcomes into short-term (≤ 1 month postintervention), medium-term (> 1 to 6 months postintervention), and long-term follow-up (> 6 months postintervention), if available. We identified 26 RCTs in this review, with 1985 people with schizophrenia or schizophrenia-like disorders, and 2056 family members. Most family-based interventions were conducted on a weekly or biweekly basis, with duration ranging from five weeks to two years. We had substantial concerns regarding the methodological quality of the included studies given that we judged all studies at high risk of performance bias and several studies at high risk of detection, attrition or reporting bias. Low-certainty evidence indicated that family-based interventions may reduce patients' relapse at one month or less postintervention (RR 0.66, 95% CI 0.49 to 0.89; 4 RCTs, 229 participants). We downgraded the evidence by two levels due to imprecision (small number of participants) and high risk of performance, detection and attrition bias. Compared to standard care, family-based interventions probably reduce caregiver burden at one month or less postintervention (MD -5.84, 95% CI -6.77 to -4.92; 8 RCTs, 563 participants; moderate-certainty evidence) and may result in more family members shifting from high to low expressed emotion (RR 3.90, 95% CI 1.11 to 13.71; 2 RCTs, 72 participants; low-certainty evidence). Family interventions may result in little to no difference in patients' death (RR 0.48, 95% CI 0.18 to 1.32; 6 RCTs, 304 participants; low-certainty evidence) and hospital admission (≤ 1 month postintervention; RR 0.81, 95% CI 0.51 to 1.29; 2 RCTs, 153 participants; low-certainty evidence) in comparison with standard care. Due to the heterogeneous measures and various follow-up periods, we were unable to provide pooled effect estimates for patients' compliance with medication and quality of life. We were very uncertain whether family interventions resulted in enhanced compliance with medication and improved quality of life for patients. We downgraded the evidence to very low certainty due to high risk of bias across studies, inconsistency (different directions of effects across studies), and imprecision (small number of participants or CIs of most studies including the possibility of no effect). This review synthesised the latest evidence on family interventions versus standard care for people with schizophrenia or schizophrenia-like disorders and their families. This review suggests that family interventions might improve patients' outcomes (e.g. relapse) and families' outcomes (e.g. caregiver burden and expressed emotion), with little to no difference in patients' hospital admission and adverse effects in terms of death. However, evidence on patients' compliance with medication and quality of life was very uncertain. Overall, the evidence was of moderate to very low certainty. Future large and well-designed RCTs are needed to provide more reliable evaluation of effects of family interventions in people with schizophrenia or schizophrenia-like disorders and their families.

Background: Chronic liver diseases (CLDs) are major contributors to hepatic disorder-related morbidity and mortality worldwide. LIV-52, a herbo-mineral product, has demonstrated anti-inflammatory and immunomodulatory properties. Objective: Several randomized controlled trials (RCTs) have been conducted to verify its hepatoprotective effects across diverse patient groups with CLDs. This study aims to perform a meta-analysis to evaluate the therapeutic efficacy of LIV-52 in liver diseases. Data Sources: PubMed, the Cochrane Library, EMBASE, and Web of Science were searched to identify eligible RCTs published through March 10, 2025, where the efficacy of LIV-52 was compared with usual treatments for liver diseases. Meta-analysis was performed using RevMan and GRADEPro software. Eligibility Criteria: RCTs comparing LIV-52 with or without standard care in patients with CLDs. Data Collection and Analysis: Data were extracted independently by two reviewers. Meta-analysis was performed using a random-effects model. Results: From the 10 RCTs involving 758 patients, the hepatoprotective effects of LIV-52 treatment were examined. Benefits were noted in the areas of appetite loss (odds ratio = 0.25, confidence interval [CI] = 0.06 to 1.00, p-value = 0.05), renormalization of the liver enzyme serum-glutamic-pyruvic transaminase (SGPT; mean difference [MD] = -16.37, CI = -30.87 to -1.88, p-value <0.03), and improvement in fat metabolism in patients with liver cirrhosis (zinc sulfate [ZnS] turbidity [MD = 6.76, CI = 2.4 to 11.12, p-value <0.002] and fecal fat secretion [MD = -1.66, CI = -2.53 to -0.75, p-value <0.0001]). However, no significant effects of LIV-52 were observed for liver enzymes such as serum-glutamic-oxaloacetic transaminase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, and the hematological parameters. The overall quality of evidence (QoE) as assessed using GRADEPro ranged from very low to moderate, with the majority of comparisons supported by low or very low due to small sample sizes and high bias risks, while the findings for some outcomes, hemoglobin and prothrombin time outcomes, supported moderate-quality evidence. Adverse events (AEs) were assessed in three RCTs; no intervention-related AEs were reported. Conclusion: The findings of this meta-analysis suggest that LIV-52 offers certain hepatoprotective benefits, particularly in improving appetite, normalizing SGPT levels, and enhancing fat metabolism in patients with liver diseases. The broader efficacy of LIV-52 is limited, and the low QoE warrants cautious interpretation. Further high-quality, large-scale studies are needed to enhance the certainty of evidence and confirm the LIV-52 efficacy and safety across all outcomes.

Background:To find out, based on the available recent randomized controlled trials (RCTs), if the nonsurgical interventions commonly used for knee osteoarthritis patients are valid and quantify their efficiency.Methods:The database of MEDLINE and EMBASE were searched for RCTs evaluating nonsurgical treatment strategies on patients with mild to moderate knee osteoarthritis. A Bayesian random-effects network meta-analysis was performed. The primary outcome was the mean change from baseline in the Western Ontario and McMaster university (WOMAC) total score at 12 months. Raw mean differences with 95% credibility intervals were calculated. Treatments were ranked by probabilities of each treatment to be the best.Results:Thirteen trials assessed 7 strategies with WOMAC at 12 months: injection of platelet rich plasma (PRP), corticosteroids, mesenchymal stem cells (MSCs), hyaluronic acid, ozone, administration of nonsteroidal anti-inflammatory drugs with or without the association of physiotherapy. For treatment-specific effect size, a greater association with WOMAC decrease was found significantly for MSCs (mean difference, −28.0 [95% CrI, −32.9 to −22.4]) and PRP (mean difference, −19.9 [95% CrI, −24.1 to −15.8]). Rank probabilities among the treatments indicated that MSCs had a much higher probability (P = .91) of being the best treatment compared with other treatments, while PRP ranked as the second-best treatment (P = .89).Conclusion:In this systematic review and network meta-analysis, the outcomes of treatments using MSCs and PRP for the management of knee osteoarthritis were associated with long-term improvements in pain and function. More high quality RCTs would be needed to confirm the efficiency of MSCs and PRP for the treatment of patients with knee osteoarthritis.

Type 2 diabetes mellitus (T2D) is associated with an increased burden of neuropsychiatric disorders, including cognitive decline, affective disorders, and substance use disorders. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), developed for glycemic control and weight reduction, have been hypothesized to confer neuroprotective and psychotropic benefits via central and peripheral mechanisms. However, evidence across individual studies remains inconsistent. We conducted a systematic review and meta-analysis (PROSPERO CRD420251025534) of randomized controlled trials (RCTs) and observational studies assessing the effect of GLP-1 RAs on neuropsychiatric outcomes. Searches were performed in MEDLINE, SCOPUS, CENTRAL, and Web of Science up to 30th October 2025. Eligible comparators included placebo, standard care, or alternative glucose-lowering agents. Data were synthesized using random-effects models, and risk of bias was assessed using RoB2 and ROBINS-I. Evidence certainty was graded using GRADE methodology. From 10,037 records, 82 studies were included. GLP-1 RAs were associated with a reduced risk of idiopathic Parkinson's disease (PD) (pooled HR 0.70, 95% CI: 0.53-0.92, I2 = 38%) but no improvements in motor symptoms in established PD (MDS-UPDRS Part III off-medication: mean difference -3.29, 95% CI: -7.84, 1.26, I2 = 80%). No consistent improvements in non-motor symptoms, quality of life, or dyskinesia scores were seen. GLP-1 RAs were associated with a reduced risk of cannabis use disorder (pooled HR 0.55, 95% CI: 0.39-0.77, I2 = 71%) but showed no significant effect on opioid use disorder (pooled HR 0.61, 95% CI: 0.24-1.52, I2 = 91%). Liraglutide reduced binge frequency in binge eating disorder (mean difference -1.28, 95% CI: -1.67, -0.89, I2 = 53%) compared to placebo. In observational studies versus non-user controls, GLP-1 RA use was associated with a lower reported risk of suicidality (pooled OR 0.34, 95% CI: 0.18-0.63, I2 = 99%), but no such association was seen with Semaglutide alone (pooled OR 0.71, 95% CI: 0.29-1.73, I2 = 99%), active-comparator studies (pooled HR 0.96, 95% CI: 0.81-1.15, I2=0%) or RCTs (pooled RR 1.13, 95% CI: 0.53-2.41, I2=0%). No associations were observed for depression or anxiety. For dementia, findings were mixed: no benefit versus SGLT2 inhibitors (pooled RR 1.07, 95% CI: 0.73-1.56, I2 = 78%), but there was a reduced risk of Alzheimer's disease when compared to unmatched or non-exposed controls (pooled RR 0.37, 95% CI: 0.14-0.96, I2 = 98%). Certainty of evidence ranged from moderate to very low. Current evidence, largely of low to very low certainty, suggests potential selective neuropsychiatric associations of GLP-1 RAs, particularly in Parkinson's disease risk reduction and binge eating disorder. Benefits for dementia risk reduction were observed primarily in comparisons with non-exposed or DPP4i, whereas no advantage was seen versus other active comparators, such as SGLT2 inhibitors. Our findings should be interpreted as hypothesis-generating due to significant heterogeneity and wide confidence intervals, indicating imprecision. Longer-term studies with neuropsychiatric outcomes as the primary endpoint are required.

Pediatric surgical patients often face considerable perioperative challenges, including anxiety and pain. Digital health interventions offer promise, but their efficacy remains uncertain. To compare the effects of digital health interventions in pediatric perioperative care. PubMed, Embase, Web of Science, CENTRAL, and CINAHL databases were searched up to March 1, 2025. Randomized clinical trials (RCTs) involving pediatric patients (aged ≤18 years) undergoing surgery with general anesthesia, where digital technology was used as a distraction intervention. A frequentist network meta-analysis with random-effects model was used to calculate standardized mean differences (SMDs) or mean differences (MDs) with 95% CIs. Interventions were ranked using P values, risk of bias assessed using the Cochrane risk of bias tool 2, and certainty of evidence rated using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Critical outcomes included pediatric preoperative anxiety, postoperative pain, emergence delirium, and induction compliance. Important but noncritical outcomes encompassed parental preoperative anxiety and postoperative satisfaction. Of 7734 RCTs screened, 49 were included involving 4535 youth (pooled mean age, 7.42 years; 95% CI, 6.85 to 7.99; 2989 [65.9%] male) with 7 interventions: virtual reality (VR), 2-dimensional (2D) games, 2D videos, interactive robots, midazolam, control (standard care), and enhanced control (eg, booklets). Compared to control, VR (SMD, -1.14; 95% CI, -1.54 to -0.74; moderate certainty), 2D videos (SMD, -1.08; 95% CI, -1.51 to -0.65; moderate certainty), 2D games (SMD, -1.02; 95% CI, -1.54 to -0.49; low certainty), and enhanced control (SMD, -0.83; 95% CI, -1.53 to -0.13; low certainty) reduced preoperative anxiety. VR (SMD, -1.09; 95% CI, -1.58 to -0.59; moderate certainty), 2D games (SMD, -0.87; 95% CI, -1.62 to -0.12; low certainty), and 2D videos (SMD, -0.56; 95% CI, -1.06 to -0.06; moderate certainty) reduced postoperative pain. VR showed the greatest effect on compliance (MD, -0.93; 95% CI, -1.62 to -0.24; moderate certainty). No significant differences compared to control. This network meta-analysis of RCTs found that VR, 2D videos, and 2D games significantly reduced pediatric perioperative anxiety and pain and improved induction compliance. These findings support the use of digital health interventions in pediatric perioperative care and their broader clinical adoption.

AimsThe optimal timing of an invasive strategy (IS) in non-ST-elevation acute coronary syndrome (NSTE-ACS) is controversial. Recent randomized controlled trials (RCTs) and long-term follow-up data have yet to be included in a contemporary meta-analysis.Methods and resultsA systematic review of RCTs that compared an early IS vs. delayed IS for NSTE-ACS was conducted by searching MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. A meta-analysis was performed by pooling relative risks (RRs) using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), recurrent ischaemia, admission for heart failure (HF), repeat re-vascularization, major bleeding, stroke, and length of hospital stay. This study was registered with PROSPERO (CRD42021246131). Seventeen RCTs with outcome data from 10 209 patients were included. No significant differences in risk for all-cause mortality [RR: 0.90, 95% confidence interval (CI): 0.78–1.04], MI (RR: 0.86, 95% CI: 0.63–1.16), admission for HF (RR: 0.66, 95% CI: 0.43–1.03), repeat re-vascularization (RR: 1.04, 95% CI: 0.88–1.23), major bleeding (RR: 0.86, 95% CI: 0.68–1.09), or stroke (RR: 0.95, 95% CI: 0.59–1.54) were observed. Recurrent ischaemia (RR: 0.57, 95% CI: 0.40–0.81) and length of stay (median difference: −22 h, 95% CI: −36.7 to −7.5 h) were reduced with an early IS.ConclusionIn all-comers with NSTE-ACS, an early IS does not reduce all-cause mortality, MI, admission for HF, repeat re-vascularization, or increase major bleeding or stroke when compared with a delayed IS. Risk of recurrent ischaemia and length of stay are significantly reduced with an early IS.