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Atopic dermatitis and the risk of osteoporosis and fractures: a meta-analysis of cohort studies.

BACKGROUND: This meta-analysis aims to evaluate the risk of osteoporosis and fractures in patients with atopic dermatitis (AD) by synthesizing data from cohort studies. We also provide a comprehensive analysis of fracture risks across different severities of AD and anatomical sites. METHODS: Following the PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Embase, and the Cochrane Library up to May 30, 2025. Studies that investigated the relationship between AD and osteoporosis or fractures were included in the analysis. Data extraction and screening were performed independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was applied, alongside sensitivity and subgroup analyses. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Ten cohort studies, involving 368 to over 2 million AD patients, were included. NOS scores ranged from 7 to 8, indicating generally high study quality. The pooled analysis revealed a 56% increased risk of osteoporosis (OR = 1.56, 95% CI: 1.14-2.13; I2&#xa0;=&#xa0;99.9%, p&#x2009;<&#x2009;0.0001) and an 8% increased risk of all-cause fractures (OR = 1.08, 95% CI: 1.05-1.10; I2&#xa0;=&#xa0;82.1%, p&#x2009;<&#x2009;0.0001) in AD patients. Subgroup analyses demonstrated a progressive increase in fracture risk with the severity of AD. Specific risks were significantly higher for vertebral fractures (OR = 1.14, 95% CI: 1.08-1.20; I2&#xa0;=&#xa0;67.3%, p&#x2009;=&#x2009;0.009) and lower limb fractures (OR = 1.11, 95% CI: 1.08-1.13; I2&#xa0;=&#xa0;65.0%, p&#x2009;=&#x2009;0.014). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected (p&#x2009;=&#x2009;0.316). CONCLUSION: AD is associated with an increased risk of osteoporosis and fractures, particularly among patients with severe AD and those experiencing vertebral or lower limb fractures. These findings highlight the importance of targeted bone health monitoring in the clinical management of AD patients.Registration: (PROSPERO: CRD420251066550).

Humans

Paediatric penile length: a systematic review and meta-analysis.

OBJECTIVE: To assess geographical variation in stretched penile length among prepubertal boys and evaluate temporal trends over the past two decades, as defining reference values for genital organ size remains crucial for early identification of development disorders. METHODS: The PubMed, Cochrane and Scopus databases (no deadlines for publishing were imposed) were searched according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Five authors independently extracted individual participant data and assessed the risk of bias. Studies with quantitative penile lengths were included; those involving congenital malformations were excluded. The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (registration number CRD42022335643). RESULTS: A total of 55 studies from 2000 to 2024 were evaluated, including data from 31&#x2009;915 boys. Pooled mean stretched penile length estimates were 3.07&#x2009;cm (95% confidence interval [CI] 2.88-3.26&#x2009;cm) for the 1-week-old boys, 3.73&#x2009;cm (95% CI 3.53-3.93&#x2009;cm) for the 1-year-old boys, 4.69&#x2009;cm (95% CI 4.49-4.88&#x2009;cm) for the 2-5&#x2009;year-old boys, and 5.43&#x2009;cm (95% CI 5.20-5.66&#x2009;cm) for the 5-10&#x2009;year- old boys. When comparing data from the 2000s to the 2020s, stretched penile length decreased by 16.2% (from 3.46 to 2.90&#x2009;cm), 16.3% (from 4.17 to 3.49&#x2009;cm), 21.5% (from 5.31 to 4.17) and 26.2% (from 6.46 to 4.77&#x2009;cm) in the 1-week-old, 1-year-old, 2-5-year-old and 5-10-year-old boys, respectively. Subgroup analysis for those aged >2&#x2009;years showed significant variations by geographical region (P&#x2009;<&#x2009;0.001). CONCLUSIONS: The present study observed large variations in penile length across geographical regions and among prepubescent boys of different ages, while also suggesting a possible decline over the past two decades.

Humans

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR&#xa0;=&#xa0;0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR&#xa0;=&#xa0;0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR&#xa0;=&#xa0;0.68, 95%-CI: 0.53-0.86) and event-free survival (HR&#xa0;=&#xa0;0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3&#xa0;years was significantly lower with haplo-cord (OR&#xa0;=&#xa0;0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

Humans

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p&#x2009;<&#x2009;0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62&#xa0;min, 95% CI 0.18-7.06; p&#x2009;<&#x2009;0.05) and reduced mean power output (mean difference&#x2009;-&#x2009;19.97 W, 95% CI&#x2009;-&#x2009;36.87 to&#x2009;-&#x2009;3.06; p&#x2009;<&#x2009;0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans

Dosimetric Parameters of the Heart and Its Substructures in Predicting Cardiac Events or Survival in Patients With Lung Cancer After Radiation Therapy: A Systematic Review and Meta-analysis.

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 &#x2265;1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans

Comparative efficacy and safety of bi-flanged metal stents versus lumen-apposing metal stents for endoscopic drainage of pancreatic fluid collections: a systematic review and meta-analysis.

INTRODUCTION: Pancreatic fluid collections (PFCs), particularly walled-off necrosis, are common complications of acute pancreatitis that often require endoscopic drainage. Bi-flanged metal stents (BFMS; NAGI; Taewoong Medical, Gyenoggi-do, Korea) and electrocautery-enhanced lumen-apposing metal stents (LAMS; AXIOS, Boston Scientific Corporation, Marlborough, Massachusetts, USA) are frequently used, but comparative data remain limited. This study aims to compare the efficacy and safety of BFMS and LAMS in the endoscopic drainage of PFCs. METHODS: This meta-analysis followed the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive database searches were conducted through November 2024 to identify studies comparing BFMS and LAMS for endoscopic ultrasound-guided drainage of PFCs. Outcomes were pooled using a random-effects model with RevMan Web, and statistical significance was defined as a P value less than 0.05. RESULTS: Three studies ( n &#x2005;=&#x2005;627; 329 BFMS and 298 LAMS) met inclusion criteria. No significant differences were observed between BFMS and LAMS for technical success [odds ratio (OR): 1.16; 95% confidence interval (CI): 0.55-2.43] or clinical success (OR: 0.97; 95% CI: 0.51-1.87). Similarly, there were no differences in walled-off necrosis recurrence (OR: 2.01; 95% CI: 0.17-24.02), number of direct endoscopic necrosectomy sessions (OR: 0.52; 95% CI: 0.05-5.12), or mean number of endoscopic procedures (mean difference: 0.18, 95% CI: 2.08-2.45). Adverse events were also comparable between groups, including bleeding (OR: 0.64), infection (OR: 1.18), stent migration (OR: 1.83), and stent occlusion/dysfunction (OR: 1.71). CONCLUSION: BFMS and LAMS provide equivalent efficacy and safety in the endoscopic ultrasound-guided drainage of PFCs. Either stent type represents a viable therapeutic option. Further large-scale prospective studies are warranted to refine stent selection strategies.

Humans

Non-genetic Risk Factors for Allopurinol-Induced Severe Cutaneous Adverse Reaction (SCAR): A Systematic Review.

BACKGROUND: Allopurinol-induced severe cutaneous adverse reactions (SCARs) are rare but potentially life threatening, particularly in Asian populations. While the genetic marker HLA-B*58:01 is a well-established risk factor, non-genetic factors may also contribute. This systematic review synthesizes evidence on associations between non-genetic risk factors and allopurinol-induced SCAR. METHODS: We searched MEDLINE, Scopus, Cochrane Library and Web of Science from inception to 29 June 2026 for observational studies examining non-genetic risk factors for SCAR, defined as Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Acute Generalised Exanthematous Pustulosis, or Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms. Adults aged &#x2265;&#xa0;18 years were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model; heterogeneity was assessed with I2. Mean differences were calculated for continuous variables. NIH Study Quality Assessment Tool was used for quality assessment of the studies. RESULTS: Twenty-six studies were included. Female sex (20 studies; 3340 SCAR cases, 562,647 controls) was associated with an increased risk of allopurinol-induced SCAR (OR 2.06; 95% confidence interval (CI) 1.25-3.38). Chronic kidney disease (16 studies; 1625 SCAR cases, 553,804 controls) was also significantly associated with SCAR (OR 3.78; 95% CI 1.99-7.17). Five studies (177 SCAR cases, 1368 controls) reported higher allopurinol doses among SCAR cases than tolerant controls (mean difference 19.61 mg; 95% CI 2.97-36.24). No significant associations were observed for age or concomitant diuretic use in the primary meta-analyses. Substantial heterogeneity was observed across studies. Sensitivity analyses demonstrated consistent findings for most factors, although concomitant diuretic use became significantly associated with SCAR after exclusion of non-Asian and zero-event studies. CONCLUSION: CKD, female sex, and higher allopurinol dose were identified as significant non-genetic risk factors for allopurinol-induced SCAR. These findings support consideration of non-genetic factors alongside pharmacogenomic screening in future risk-stratification strategies. However, substantial heterogeneity and potential publication bias limit the certainty of the available evidence. Well-designed studies evaluating non-genetic predictors as primary outcomes are needed to develop robust integrated risk prediction models for clinical decision making.

Journal Article

Comparison of Ketamine and Pregabalin on Postoperative Opioid Usage and Pain Management in Spinal Fusion: Systematic Review and Network Meta-analysis.

BACKGROUND CONTEXT: Spinal fusion is associated with substantial early postoperative pain and opioid exposure. Both ketamine and pregabalin are widely incorporated into Enhanced Recovery After Surgery (ERAS) protocols as opioid-sparing adjuncts. However, their comparative efficacy and safety in this specific setting remain uncertain. Our objective was to compare ketamine and pregabalin indirectly for early postoperative opioid consumption, pain, and adverse events in adults undergoing spinal fusion. METHODS: Pubmed, Embase, and Cochrane Trials were searched from inception through October 2025. Eligible studies were randomized trials enrolling adults undergoing instrumented spinal fusion, randomized to perioperative ketamine, pregabalin, or control, and reported extractable 24-hour opioid consumption or pain outcomes. Continuous outcomes were pooled as mean differences in MME or VAS units, and adverse events were reported descriptively. A connected treatment network was analyzed using random-effects models. Risk of bias (RoB) was assessed with the Cochrane RoB 2 tool. RESULTS: Thirteen trials (n=879) were included: ketamine (n=210), pregabalin (n=271), and control (n=398). Six trials contributed opioid data (3 ketamine, 3 pregabalin). Using pregabalin 150 mg as reference, ketamine was associated with lower 0-24-hour opioid use (MD -56.99 mg MME; 95% CI -99.56 to -14.43). Control (MD +21.31; 95% CI -1.05 to +43.66) and pregabalin 300 mg (MD -13.22; 95% CI -40.41 to +13.96) did not significantly differ from pregabalin 150 mg. Seven trials contributed 24-hour VAS data, with control being associated with higher pain versus pregabalin 150 mg (MD +0.84; 95% CI +0.01 to +1.66), while ketamine and pregabalin 300 mg were not k significantly different. Adverse events were generally infrequent and similar to control. CONCLUSIONS: Both ketamine and pregabalin provide early opioid sparing with comparable 24-hour analgesia. Ketamine showed a larger opioid-sparing point estimate, but indirect comparisons are imprecise. Adequately powered head-to-head trials with standardized protocols and adverse event reporting are needed.

Humans

Minimally invasive versus open abdominoperineal resection and the risk of postoperative perineal hernia: a systematic review and meta-analysis.

BACKGROUND: The impact of minimally invasive surgery on the risk of postoperative perineal hernia after abdominoperineal resection (APR) or extralevator abdominoperineal excision (ELAPE) remains uncertain. This study compares perineal hernia rates and perioperative outcomes between minimally invasive and open approaches. METHODS: PubMed, Scopus, Web of Science, and Cochrane Library were searched through June 2026. Pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. A Bayesian meta-analysis was additionally performed for the primary outcome. RESULTS: Four comparative observational studies involving 763 patients were included; 249 underwent minimally invasive APR/ELAPE, and 514 underwent open APR/ELAPE. Postoperative perineal hernia was significantly more frequent following minimally invasive surgery (OR 4.13; 95% CI 2.24-7.61; p&#x2009;<&#x2009;0.001). Intraoperative blood loss was significantly lower in the minimally invasive group (MD&#x2009;-&#x2009;156.5 mL; 95% CI&#x2009;-&#x2009;298.4 to -&#x2009;14.5; p&#x2009;=&#x2009;0.03), as was operative time (MD&#x2009;-&#x2009;41.7&#xa0;min; 95% CI&#x2009;-&#x2009;60.8 to -&#x2009;22.5; p&#x2009;<&#x2009;0.01). No significant differences were observed in hospital stay (MD&#x2009;-&#x2009;2.5 days; 95% CI&#x2009;-&#x2009;5.4 to 0.4; p&#x2009;=&#x2009;0.09) or 30-day readmission rates (OR 1.41; 95% CI 0.82-2.42; p&#x2009;=&#x2009;0.209). Bayesian analysis yielded a posterior mean OR of 4.04 (95% CrI 1.96-8.36), corresponding to a 99.9% posterior probability that minimally invasive surgery increases the risk of postoperative perineal hernia. CONCLUSION: Minimally invasive APR/ELAPE was associated with an increased risk of postoperative perineal hernia compared with the open approach. Strategies to reduce this complication while preserving the benefits of minimally invasive surgery warrant further investigation.

Humans

Nonoperative Management is Associated With Similar Long-Term Patient-Reported Outcomes Compared With Surgery for Cervical Radiculopathy: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare long-term patient-reported outcomes between surgical and nonoperative management for cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Cervical radiculopathy is a common condition associated with substantial morbidity. While both surgical and nonoperative approaches are effective, it remains unclear which patients benefit most from each strategy and whether earlier operative intervention confers meaningful long-term advantage. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to January 2026 for randomized and observational studies comparing surgical and nonoperative management for cervical radiculopathy. Primary outcomes included visual analog scale (VAS) scores for neck and arm pain, neck disability index (NDI), and overall clinical success. Secondary outcomes included analgesia use and sick leave. Random-effects meta-analyses were performed using restricted maximum likelihood estimation. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. RESULTS: Eleven studies comprising 1154 patients (surgical: 522; nonoperative: 632) were included. Surgery was not associated with superior outcomes in VAS for arm pain (MD: -0.67, 95% CI: -1.59 to 0.26, P =0.12), VAS for neck pain (MD: -0.50, 95% CI: -1.38 to 0.38; P =0.19), or NDI (MD: -3.69, 95% CI: -9.63 to 2.25, P =0.16) after 12 months of treatment, nor in overall success (RR: 1.11, 95% CI: 0.93-1.34, P =0.21). No significant differences were observed in analgesia use ( P =0.54) or sick leave ( P =0.48) at last follow-up. Most studies were rated serious risk of bias and overall certainty of evidence was moderate. CONCLUSION: Evidence from this pooled analysis suggests that long-term pain, disability, and functional outcomes are comparable between patients selected for nonoperative management and those selected for surgery. These findings reflect outcomes within selected cohorts and should not be interpreted as evidence of therapeutic equivalence. LEVEL OF EVIDENCE: Level II.

Humans

Robot-assisted versus manual percutaneous vascular interventions across vascular territories: a systematic review and meta-analysis.

Robot-assisted percutaneous vascular intervention (R-PVI) has expanded beyond coronary procedures, but previous reviews were largely coronary-focused and observational. Recent randomized controlled trials (RCTs) warrant broader reassessment of R-PVI versus manual percutaneous vascular intervention (M-PVI) across vascular territories. PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from database inception to January 31, 2026, following PRISMA guidelines. RCTs and observational studies including &#x2265;10 adult patients in total were eligible. Comparative studies informed primary analyses, while single-arm studies provided supportive evidence. Primary outcomes were clinical success rate and major adverse cardiovascular/cerebrovascular events (MACE) rate. Secondary outcomes included mortality rate, technical success rate, procedural time metrics, contrast volume, and radiation exposure. Random-effects models were used. Forty studies were included: 3 RCTs, 10 comparative observational studies, and 27 single-arm observational studies, comprising 3,870 patients undergoing R-PVI and 1,142 undergoing M-PVI. Comparative analyses showed similar clinical success rates (RR 1.00, P = 0.46), MACE rates (RR 0.72, P = 0.43), and mortality. Single-arm pooled estimates for clinical and technical success were 98.76% and 96.09%, respectively. R-PVI prolonged total procedure time overall (MD 15.92&#xa0;min, P = 0.01), with consistent increases in the neurovascular, RCT, and non-RCT subgroups. Fluoroscopy time was also longer (MD 1.91&#xa0;min, P = 0.04), mainly in the RCT subgroup (MD 2.83&#xa0;min, P = 0.001). In contrast, intravascular intervention time was unchanged overall and in RCTs, but was prolonged in non-RCTs (MD 8.72&#xa0;min, P = 0.006). Operator radiation exposure was markedly reduced (MD -33.97 &#x3bc;Sv, P < 0.001), whereas patient radiation exposure and contrast volume were similar. R-PVI appears feasible and safe across selected vascular procedures. Its clearest benefit is reduced operator radiation exposure, whereas lower whole-procedure efficiency remains its main limitation.

Humans

Effects of single-injection vs. continuous brachial plexus blocks for shoulder surgeries on patient-reported outcomes: a systematic review and meta-analysis with trial sequential analysis of randomised controlled trials.

INTRODUCTION: Single-injection and continuous brachial plexus block techniques are used widely for postoperative analgesia in patients undergoing shoulder surgery. Although patient-reported outcomes are described in individual studies, their effects have not been synthesised comprehensively using a patient-centred framework. We sought to compare the effects of single-injection vs. continuous brachial plexus block techniques on patient-reported outcomes in adult patients following elective shoulder surgery. METHODS: Databases were searched from inception to October 2025 and randomised controlled trials reporting patient-reported outcomes were included. Co-primary outcomes were postoperative patient-reported pain intensity at rest and during movement at 12&#x2009;h, 24&#x2009;h and 48&#x2009;h post-surgery. Secondary outcomes included nausea and vomiting; sleep quality; patient satisfaction; opioid requests; and functional scores. Random-effects meta-analysis and trial sequential analysis were performed, with risk of bias and quality of patient-reported outcome reporting assessed. RESULTS: Twenty randomised controlled trials that included 1198 patients were analysed. Continuous brachial plexus blocks were associated with lower pain at rest at 12&#x2009;h, 24&#x2009;h and 48&#x2009;h, with mean differences (MD) of -1.96 (95%CI -2.81 to -1.11, p&#x2009;<&#x2009;0.001), -1.66 (95%CI -2.27 to -1.05, p&#x2009;<&#x2009;0.001) and&#x2009;-&#x2009;1.18 (95%CI -1.84 to -0.53, p&#x2009;<&#x2009;0.001), respectively. Pain on movement could only be pooled at 24&#x2009;h and 48&#x2009;h and showed MD -2.04 (95%CI -4.26-0.19, p&#x2009;=&#x2009;0.07) and&#x2009;-&#x2009;1.30 (95%CI -3.67-1.07, p&#x2009;=&#x2009;0.28) respectively. The co-primary outcomes approached or exceeded the predefined minimal clinically important difference for pain scores after shoulder surgery, in favour of continuous techniques. DISCUSSION: Continuous brachial plexus blocks are associated with better pain at rest and other patient-centred outcomes following shoulder surgery, while effects on dynamic pain and long-term functional recovery remain uncertain.

Humans

Proficiency-based training and evidence-based methodology: a systematic review and meta-analysis.

OBJECTIVE: To assess adherence of self-labelled proficiency-based progression (PBP) studies to evidence-based PBP criteria and examine associations with training outcomes. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews. PubMed, CENTRAL, EMBASE, MEDLINE, and Scopus were searched from inception to 1 March 2023. Prospective English-language studies on healthcare procedural training reporting objective performance outcomes were included; non-prospective, non-quantitative, non-procedural, non-English studies, and reviews were excluded. Pre-specified outcomes included adherence to 18 evidence-based PBP criteria and objective performance metrics (errors, steps, time); secondary outcomes included proficiency benchmark achievement and Likert ratings. Data extraction was performed independently by multiple reviewers. Study quality was assessed using the Medical Education Research Study Quality Instrument and risk of bias by two investigators. Effect sizes were pooled using random-effects models (DerSimonian-Laird), expressed as the ratio of means (ROM) for continuous outcomes and bias-corrected odds ratios for dichotomous outcomes. RESULTS: Of 646 studies identified 175 met inclusion criteria. In the PBP studies (n&#x2009;=&#x2009;18), 94% fulfilled minimum criteria (use of a proficiency benchmark, its quantitative definition, and requirement for demonstration prior to progression) vs 36% of non-PBP studies (n&#x2009;=&#x2009;157). If all PBP criteria were included, 83% of PBP studies used these criteria vs only 2% of non-PBP-studies. In quantitative analysis (27 randomised clinical studies, 761 participants), ROM results showed that PBP training reduced the number of performance errors by 58% (P&#x2009;<&#x2009;0.001) and procedural time by 28% (P&#x2009;=&#x2009;0.006), increasing number of steps performed by 22% (P&#x2009;=&#x2009;0.03). When stratified based on number of criteria fulfilled, meta-regression demonstrated that increasing the number of PBP criteria fulfilled was associated with progressive and systematic trainee performance improvement. CONCLUSIONS: The more training methodologies adhere to established PBP criteria, the better training outcome will be.

Humans

Reliability, Device Agreement and Validity of Load-Velocity Profiles: A Systematic Review with Meta-analysis.

BACKGROUND: For a valid one-repetition maximum (1RM) prediction via load-velocity (LV) relationships, high reliability and accuracy must be assumed. OBJECTIVE: Since individual study results indicate ambivalent prediction, this systematic review and meta-analysis was designed to provide a updated and comprehensive overview, extending knowledge about the validity and reliability of commercially available velocity sensors in Part I and the validity and reliability of velocity-based 1RM prediction models in Part II. METHODS: A systematic literature search was conducted in PubMed/MEDLINE, Web of Science, and Scopus. Validity and/or reliability studies or velocity-based 1RM prediction evaluations were included. Methodological quality was assessed using adapted COSMIN. The analysis was performed for intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC), and Pearson's correlation coefficient (r). The review was preregistered in PROSPERO (CRD42025634595). RESULTS: Sixty-three studies were included for sensor validity and reliability and 38 for 1RM prediction models. Part I: Velocity sensors demonstrated good-to-excellent pooled validity and device agreement (ICC&#x2009;=&#x2009;0.91-0.92 [0.83-0.97]; k&#x2009;=&#x2009;55 and 439, respectively); intra- and inter-day reliability were classified as good to excellent with ICC&#x2009;=&#x2009;0.90-0.91 [0.85-0.95] (k&#x2009;=&#x2009;228 and 608, respectively), with sensor technology moderating the results. However, substantial heterogeneity and wide ranges of study-level estimates indicated considerable variability across moderators, linear position transducer (LPT) generally showing more consistent performance than inertial measurement units (IMU). Part II: Velocity-based 1RM prediction showed ICCs&#x2009;=&#x2009;0.90 [0.83-0.94] (k&#x2009;=&#x2009;124) and ICC&#x2009;=&#x2009;0.91 [0.72-0.98] (k&#x2009;=&#x2009;9); for reliability and validity, respectively. DISCUSSION: Commercial velocity sensors generally provide high relative validity and reliability. Results varied depending on exercise complexity, intensity, sensor technology, and modeling approach. While velocity-based 1RM prediction demonstrated high average validity, large heterogeneity in lower body exercises significantly biased the results. Furthermore, the dearth of measurement error and agreement analyses prohibits final conclusions. CONCLUSION: Therefore, velocity-based monitoring and 1RM prediction require cautious interpretation, as sensor- and exercise-specific evidence remains limited.

Load&#x2013;velocity relationship

Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

Humans

Efficacy and Safety of Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.

BACKGROUND: Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS: PubMed, Cochrane, and EMBASE were searched for randomized controlled trials (RCTs) and nonrandomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS: A total of 39,991 participants across 6 studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (relative risk [RR] = 0.84, 95% confidence interval [CI] 0.78-0.91, P < 0.001), risk of acute limb ischemia (RR = 0.65, 95% CI 0.55-0.78, P < 0.001), and thromboembolism (RR = 0.60, 95% CI 0.38-0.97, P = 0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR = 0.50, 95% CI 0.30-0.85, P = 0.003). However, its use was associated with a significantly higher risk of major bleeding (hazard ratio [HR] = 1.54, 95% CI 1.38-1.72, P < 0.001) and International Society on Thrombosis and Hemostasis-defined bleeding (RR = 1.45, 95% CI 1.19-1.76, P < 0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION: Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.

Humans

Closed-loop vasopressor systems for hemodynamic control in perioperative and critical care settings: a systematic review and meta-analysis.

Maintaining mean arterial pressure (MAP) within a predefined target is central to haemodynamic management in surgical and critically ill adults receiving vasopressors. Closed-loop vasopressor (CLV) systems automate titration to optimise blood pressure control, but their clinical effectiveness remains uncertain. We performed a systematic review and meta-analysis comparing CLV with manual titration. This PRISMA 2020-compliant review was prospectively registered in PROSPERO (CRD420250655697). MEDLINE, Embase, Scopus, Web of Science, CENTRAL, and the Cochrane Library were searched (January 2000-June 2025). Randomised controlled trials enrolling adults receiving vasopressors in perioperative or intensive care settings were included. Primary outcomes were time within the MAP target range and time spent in hypotension or hypertension. Risk of bias was assessed using RoB 2.0 and certainty of evidence using GRADE. Random- or fixed-effects models were selected according to heterogeneity. Six randomized controlled trials (215 patients) were included in the systematic review, whereas five perioperative trials contributed to the meta-analysis of haemodynamic control outcomes, and one ICU-based study was summarized narratively because it did not report comparable MAP control endpoints. CLV increased time within the MAP target range (mean difference [MD] 33.94%, 95% CI 20.41-47.46; I2&#x2009;=&#x2009;77%) and reduced time in hypotension (MD&#x2009;-&#x2009;18.24%, 95% CI&#x2009;-&#x2009;28.95 to&#x2009;-&#x2009;7.53; I2&#x2009;=&#x2009;73%). There was no significant difference in time in hypertension, cumulative norepinephrine dose, or major/minor adverse events. ICU length of stay was not pooled because of clinical and methodological heterogeneity. Certainty of evidence ranged from low to high (moderate for haemodynamic control outcomes). CLV systems improved haemodynamic control, primarily in perioperative settings,&#xa0;but heterogeneity and small samples limit confidence in effect size and generalisability.&#xa0;Evidence in critically ill populations remains limited, and larger trials are needed to determine whether improvements in these physiological surrogate endpoints translate into meaningful patient-centred outcomes.

Humans

Efficacy and Safety of Anti-Obesity Medications for Weight Loss Maintenance in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

AIMS: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of anti-obesity medications (AOMs) for long-term weight maintenance following initial weight loss in adults with overweight or obesity. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library from inception to 31 October 2025. Eligible studies were randomised controlled trials (RCTs) comparing AOMs with placebo during the weight-maintenance phase in adults with overweight or obesity after initial weight loss achieved through lifestyle, dietary, surgical or pharmacological interventions. Outcomes included anthropometric indices, cardiometabolic measures, safety endpoints, quality of life and neuropsychiatric adverse events. Weighted mean differences (WMDs) and odds ratios (ORs), each with 95% confidence intervals (CIs), were pooled for continuous and categorical outcomes, respectively, using fixed-effect or random-effects models as appropriate. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE framework. The protocol was registered with PROSPERO (CRD420261293040). RESULTS: A total of 12 RCTs comprising 4915 participants met the inclusion criteria. Compared with placebo, AOM therapy during the weight-maintenance phase was associated with prevention of weight regain and additional improvements in anthropometric and cardiometabolic outcomes. AOMs led to further reductions in body weight (BW, WMD: -8.68&#x2009;kg, 95% CI: -13.25 to -4.11), waist circumference (WC, WMD: -7.16&#x2009;cm, 95% CI: -10.34 to -3.98) and body mass index (BMI, WMD: -3.58&#x2009;kg/m2, 95% CI: -5.69 to -1.46). Additional benefits were observed for triglycerides, total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure and diastolic blood pressure. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Neuropsychiatric adverse events were generally comparable between groups, and available quality-of-life measures favoured AOM treatment. CONCLUSIONS: AOM therapy during the weight-maintenance phase can help prevent weight regain, provide further reductions in body weight and improve cardiometabolic risk factors in adults with overweight or obesity. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Further long-term trials are needed to clarify optimal treatment strategies and safety.

Humans