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Endoscopic submucosal dissection for locally recurrent gastric neoplasia following endoscopic resection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for locally recurrent gastric neoplasia following endoscopic resection (ER) is technically challenging because of scar-related submucosal fibrosis. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of salvage ESD in this setting. METHODS: Multiple databases were searched through December 2025 for studies reporting ESD outcomes for locally recurrent gastric lesions at or contiguous with a prior ER scar. Primary outcome was curative resection and need for surgery. Secondary outcomes were en bloc and R0 resection, local recurrence, delayed bleeding, and perforation. Meta-analyses were performed using a random effects model. Heterogeneity was assessed using I2. RESULTS: Seven studies (259 patients; 265 ESDs) were included. Across 5 studies and 243 ESDs, pooled curative resection rate was 69.7% (95% CI, 60.6-78.1; I2 = 38%), while 8.2% (95% CI, 3.3-14.6; I2 = 38.4%) required surgery. En bloc resection rate was 92.3% (95% CI, 79.1-99.7; I2 = 83.7%) across 6 studies, and pooled R0 resection rate was 87.5% (95% CI, 82.1-92.2; I2 = 0%) across 4 studies. Over a mean follow-up of 42 months, pooled local recurrence was 2.0% (95% CI, 0.0-9.7; I2 = 54.1%) across 6 studies. Delayed bleeding was 4.1% (95% CI, 0.8-9.0; I2 = 40.8%) and perforation was 4.1% (95% CI, 1.6-7.3; I2 = 0%). CONCLUSIONS: ESD for locally recurrent gastric neoplasia after ER achieves acceptable curative resection, high en bloc/R0 resection, and low local recurrence and morbidity. It is a viable organ-preserving option for appropriately selected patients, ideally performed at expert centers with close surveillance.

Humans

Prevalence of psychosis in South Asia: A systematic review and meta-analysis.

BACKGROUND: Psychotic disorders are a major contributor to global disability, yet prevalence data from South Asia which inhabits a quarter of the world's population, remain limited. Reliable estimates are essential for health service planning, policy, and closing the substantial treatment gap. This review provides the first comprehensive synthesis of psychosis prevalence across South Asia. METHODS: We searched PubMed, Embase, Web of Science, Global Health, and Medline to 18 December 2024 for DSM- or ICD-based prevalence studies in Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. Cross-sectional and longitudinal studies in community or clinical populations were included. Study quality was assessed using the Joanna Briggs Institute checklist. Random-effects meta-analyses estimated pooled prevalence using the logit transformation. Heterogeneity was explored with meta-regression of key methodological variables (publication year, diagnostic system, residential setting). FINDINGS: Thirty-one studies from five countries were included. Among community-dwelling adults, pooled point prevalence was 0.85% and lifetime prevalence was 1.40%, with inter-country differences (India 1.18%, Pakistan 2.13%, Nepal 2.90%). Clinical samples showed substantially higher proportions of individuals with psychosis in service settings (11.44%), reflecting concentration of cases in treatment-seeking samples. Data for children and adolescents were limited and summarised narratively. Heterogeneity was high across meta-analyses, and exploratory meta-regression did not identify any significant moderators. INTERPRETATION: Psychosis prevalence estimates in South Asia appear higher than global averages but should be interpreted cautiously due to substantial heterogeneity and methodological variation; nevertheless, they highlight the need for culturally sensitive screening, improved detection, and strengthened mental health services.

Humans

Efficacy of high-intensity laser therapy versus ultrasound therapy in patients with knee osteoarthritis: a randomized controlled trial.

PURPOSE: High-intensity laser therapy (HILT) and ultrasound (US) are widely used for knee osteoarthritis (KOA), but comparative efficacy data remain scarce. This study compared HILT and US as exercise adjuncts in patients with KOA. METHODS: In this single-center, assessor-blinded RCT, 66 adults with KOA were randomized 1:1 to HILT or US twice weekly for 6&#xa0;weeks as exercise adjuncts. The primary outcome was WOMAC total score change from baseline to 12&#xa0;weeks post-treatment (minimum important change [MIC]&#x2009;=&#x2009;10 points, applied as an approximation). Secondary outcomes included VAS, OKS, KOOS, and EQ-5D-5L. RESULTS: In ITT analysis (N&#x2009;=&#x2009;66), the HILT group achieved a mean WOMAC reduction of 40.0 vs 8.2 points (adjusted between-group difference: -27.7 points, 95% CI:&#x2009;-&#x2009;39.0 to&#x2009;-&#x2009;16.5; p&#x2009;<&#x2009;0.001, partial &#x3b7;2&#x2009;=&#x2009;0.277). At 12&#xa0;weeks post-treatment, greater improvements across all secondary outcomes were observed in exploratory analyses (p&#x2009;&#x2264;&#x2009;0.012). Furthermore, HILT maintained therapeutic effects up to 12&#xa0;weeks post-treatment, whereas the US group experienced a gradual loss of post-treatment gains. CONCLUSION: HILT combined with exercise produced greater short-term improvements in WOMAC total score than US in patients with KOA, with exploratory findings suggesting consistent benefits in pain, function, and quality of life, and with benefits maintained up to 12&#xa0;weeks after the last treatment session.

Humans

Randomized controlled trial comparing 7-day fexuprazan-based and 14-day rabeprazole-based triple therapies for Helicobacter pylori eradication.

BACKGROUND: Fexuprazan is a newly developed potassium-competitive acid blocker used for the treatment of acid-related gastrointestinal diseases; however, clinical data regarding its efficacy in Helicobacter pylori eradication are lacking. This study evaluated the efficacy and safety of a 7-day fexuprazan-based triple therapy regimen compared with a 14-day rabeprazole-based triple therapy regimen for H. pylori infection in Korean patients. METHODS: A randomized controlled single-center study was conducted to compare the eradication rates between 7-day fexuprazan (40&#x2009;mg)-based triple therapy (with 1&#x2009;g amoxicillin and clarithromycin 500&#x2009;mg administered twice daily) and 14-day rabeprazole (20&#x2009;mg)-based triple therapy for H. pylori eradication. The primary endpoint was the success rate of H. pylori eradication, determined using the 13C-urea breath test. Safety outcomes were also evaluated. RESULTS: A total of 79 patients were randomly assigned to the fexuprazan and rabeprazole groups. In the full analysis set, eradication rates were 80.00% (32/40) in the fexuprazan group and 82.05% (32/39) in the rabeprazole group. In the per-protocol set, eradication rates were 83.78% (31/37) and 88.89% (32/36), respectively (P = 1.000 and P =.737). The overall incidence of treatment-emergent adverse events was 70.00% (28/40) in the fexuprazan group and 66.67% (26/39) in the rabeprazole group, with no significant difference between groups (P =.812); both regimens were well tolerated. Among patients with clarithromycin-susceptible strains in full analysis set, eradication rates were 93.10% (27/29) in the fexuprazan group and 87.09% (27/31) in the rabeprazole group (P =.672). In the per-protocol set, eradication rates for susceptible strains were 96.42% (27/28) in the fexuprazan group and 93.10% (27/29) in the rabeprazole group (P = 1.000). CONCLUSION: Seven-day fexuprazan-based triple therapy demonstrated eradication efficacy comparable with that of 14-day rabeprazole-based therapy in treatment-na&#xef;ve Korean patients with H. pylori infection. The fexuprazan-based regimen showed a similar safety profile and comparable incidence of adverse events with that of the rabeprazole-based regimen.

Humans

Esketamine vs. sufentanil for quality of recovery after outpatient gynecological surgery: a randomized clinical trial.

BACKGROUND: Perioperative administration of esketamine has been reported to improve early quality of recovery (QoR). However, data on its effects in outpatient surgery are limited. This study aimed to assess the impact of esketamine on QoR in patients undergoing outpatient gynecological procedures. METHODS: In this investigator-initiated, double-blind, randomized clinical trial, patients aged 18-65&#x2009;years scheduled for outpatient gynecological surgery under sedation were allocated to receive esketamine (0.2&#x2009;mg/kg) or sufentanil (0.1&#x2009;&#x3bc;g/kg) combined with propofol (1.5-3&#x2009;mg/kg). The primary outcome was quality of recovery on postoperative day (POD) 1. Secondary outcomes included quality of recovery on POD2, sedation success rate, length of post-anesthesia care unit (PACU) stay, injection pain, postoperative pain, nausea and vomiting, fatigue, patient and clinician satisfaction, sleep quality, and anxiety and depression. RESULTS: A total of 126 patients were randomized, with 63 assigned to the esketamine group and 63 to the sufentanil group. Of these, 125 patients were included in the final analysis (62 in the esketamine group and 63 in the sufentanil group), as one patient lacked follow-up data. The mean (SD) QoR-15 score on POD1 was 137.9 (14.5) in the esketamine group and 137.8 (10.7) in the sufentanil group, with no significant difference between groups (absolute difference, 0.2; 95% CI, -4.2 to 4.6; p&#x2009;=&#x2009;0.93). For secondary outcomes, the esketamine group had a longer PACU stay (median, 28.0 vs. 23.0&#x2009;min; p&#x2009;<&#x2009;0.001), a lower incidence of severe injection pain (22.6% vs. 50.8%; p&#x2009;=&#x2009;0.002), a higher proportion of patients with pain scores &#x2265; 4 at 30&#x2009;min postoperatively (30.6% vs. 6.3%; p&#x2009;=&#x2009;0.001), and higher fatigue scores (median, 3.0 vs. 2.0; p&#x2009;=&#x2009;0.01). Other secondary outcomes did not differ significantly between groups. CONCLUSION: Among patients undergoing sedation for outpatient gynecological procedures, esketamine did not significantly improve quality of recovery on POD1 compared to sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500098466.

Humans

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans

Intravenous lidocaine reduces the propofol EC50 for loss of consciousness and intraoperative anesthetic consumption in gynecological laparoscopy: A randomized controlled trial.

BACKGROUND: Intravenous lidocaine reduces propofol requirements and procedure-related adverse events. OBJECTIVES: The study aimed to test whether intravenous lidocaine would reduce the effect-site concentration of propofol required to achieve loss of consciousness and decrease propofol consumption during total intravenous anesthesia in gynecological laparoscopy. METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial. Sixty patients were randomly allocated to receive either intravenous lidocaine (1.5 mg&#xb7;kg-&#xb9; bolus) followed by continuous infusion or an equal volume of saline. Propofol was administered via target-controlled infusion starting at an effect-site concentration of 3.5 &#x3bc;g/mL. The concentration was then adjusted in steps of 0.5 &#x3bc;g/mLaccording to Dixon's up-and-down sequential method: decreased if loss of consciousness was achieved, or increased if not. Loss of consciousness was defined as loss of response to verbal commands. The median effective concentration (EC50) of propofol for inducing loss of consciousness was calculated using the Dixon's up-and-down method. General anesthesia was maintained with propofol and remifentanil, guided by state entropy (target 40-60) and surgical pleth index (target 20-50). Drug consumption was normalized to anesthesia duration and body weight. RESULTS: The estimated EC50 of propofol for inducing loss of consciousness was significantly lower in the lidocaine group than in the saline group (3.32 &#x3bc;g/mL, 95% Confidence Interval (CI): 3.04-3.59 vs. 3.89 &#x3bc;g/mL, 95% CI: 3.50-4.28). Under the study protocol, the lidocaine group also required less propofol (8.62 mg&#xb7;kg-1&#xb7;h-1, 95% CI: 8.10-9.15 vs. 9.89 mg&#xb7;kg-1&#xb7;h-1, 95% CI: 9.05-10.73) and less remifentanil (0.23 &#x3bc;g&#xb7;kg-1&#xb7;min-1, 95% CI: 0.21-0.24 vs. 0.27 &#x3bc;g&#xb7;kg-1&#xb7;min-1, 95% CI: 0.24-0.30) compared with the saline group. CONCLUSION: Intravenous lidocaine reduced the propofol EC50 for Loss of Consciousness (LOC) and decreased intraoperative propofol and remifentanil consumptions in patients undergoing gynecological laparoscopy. These findings suggest a propofol- and opioid-sparing effect of intravenous lidocaine in this setting, although confirmation in larger multicenter trials is needed.

Humans

The knee-ankle link: impact of knee varus severity on distal joint malalignment and concomitant pathologies.

BACKGROUND: Knee varus deformity is traditionally managed as an isolated joint pathology; however, persistent distal symptoms following proximal realignment suggest a more extensive kinetic chain dysfunction. The degree to which knee varus severity dictates distal malalignment and secondary pathologies remains poorly quantified in the current literature. METHODS: This systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines (PROSPERO: CRD420261363327). A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was performed from inception to April 2026. Studies examining the relationship between knee varus (HKA angle) and radiographic distal alignment or pathologies were included. Data synthesis utilized random-effects models, with prevalence analyzed via generalized linear mixed models (GLMM). RESULTS: Fourteen studies were included in the final synthesis. While pooling of continuous radiographic parameters was limited by high statistical heterogeneity in Talar Tilt (I2&#xa0;=&#xa0;96.5%), individual large-cohort data (Huang et al.) indicated that severe knee varus (HKA&#xa0;>&#xa0;10&#xb0;) was associated with increased odds of concomitant ankle osteoarthritis (OR 2.29; 95% CI 1.28-4.11) and a specific cohort prevalence of 37.1%. Furthermore, single-arm prevalence data revealed divergent trends across different study populations, with compensatory hindfoot valgus reaching 69.9% in some cohorts and rigid varus up to 63.9% in others. CONCLUSIONS: Severe genu varum is associated with distal kinetic chain alterations and concomitant ankle pathologies. However, due to the extreme heterogeneity and divergent distal adaptations observed across different cohorts, standardized knee-centric protocols may be insufficient. Further longitudinal and interventional studies are required to establish phenotype-specific rehabilitation guidelines.

Humans

Efficacy and safety of pantoprazole for stress-ulcer prophylaxis in critically ill patients: A systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Stress-related mucosal damage (SRMD) is common in critically ill patients, and pharmacologic prophylaxis remains essential. This study evaluated the efficacy and safety of pantoprazole for stress-ulcer prophylaxis in ICU patients. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted per PRISMA-2020 guidelines. PubMed, Scopus, and CENTRAL were searched for studies comparing pantoprazole with placebo in adult and pediatric ICU patients. The primary outcome was clinically important gastrointestinal (GI) bleeding; secondary outcomes included mortality, ventilator-associated pneumonia (VAP), and Clostridioides difficile infection. RESULTS: Seven RCTs (n&#xa0;&#x2248;&#xa0;9127; pantoprazole&#xa0;=&#xa0;4575; placebo&#xa0;=&#xa0;4552) were included. Pantoprazole significantly reduced clinically important GI bleeding (RR&#xa0;=&#xa0;0.53; 95% CI 0.29-0.94; p&#xa0;=&#xa0;0.03) without affecting overall mortality (RR&#xa0;&#x2248;&#xa0;0.99 [95% CI 0.92-1.05]; p&#xa0;=&#xa0;0.68). Infection rates were similar between groups (VAP: RR&#xa0;=&#xa0;0.99; p&#xa0;=&#xa0;0.78; C. difficile: RR&#xa0;=&#xa0;1.11; p&#xa0;=&#xa0;0.73). Sensitivity analyses confirmed robustness. CONCLUSIONS: Pantoprazole effectively reduces clinically important GI bleeding without increasing infection or overall mortality.

Pantoprazole

Application of SPI-guided analgesia in laparoscopic gynecologic surgery: a randomized controlled trial evaluating the remifentanil-sparing effect and predictive value of time-weighted SPI.

This study aimed to achieve two primary objectives: (1) to evaluate the opioid-sparing effect of Surgical Pleth Index (SPI)-directed analgesia during surgery via a randomized controlled trial (RCT), and (2) to propose and preliminarily assess a novel dynamic metric, Threshold-based Time-Weighted SPI (Tb-TW-SPI), which integrates stimulus intensity and duration, for its predictive efficacy regarding postoperative moderate-to-severe pain. Employing an RCT combined with exploratory analysis, 61 patients undergoing elective laparoscopic gynecologic surgery were randomized into an SPI-directed analgesia group or a conventional analgesia group. The primary outcome was total intraoperative remifentanil consumption. Postoperatively, an exploratory analysis of the control group data evaluated the correlation between Tb-TW-SPI and Numeric Rating Scale (NRS) pain scores in the post-anesthesia care unit (PACU), calculating its predictive value for moderate-to-severe pain (NRS&#x2009;&#x2265;&#x2009;4). Results: The SPI-directed group required significantly less intraoperative remifentanil than the conventional group [median (IQR): 5.84(5.02,6.62)vs. 6.96(5.81,8.19)&#xb5;g/kg/h; P&#x2009;=&#x2009;0.016]. Postoperative pain scores did not differ significantly between groups (P&#x2009;>&#x2009;0.05). Exploratory analysis of the conventional analgesia group revealed that Tb-TW-SPI values were significantly higher in patients with moderate-to-severe postoperative pain (NRS&#x2009;&#x2265;&#x2009;4) compared to those without (P&#x2009;=&#x2009;0.0417).The area under the ROC curve for Tb-TW-SPI predicting this pain was 0.74 (95% CI: 0.52-0.96), with 67% sensitivity and 76% specificity at an optimal cutoff of 1210. This RCT suggests that SPI-directed analgesia can safely and moderately reduce intraoperative remifentanil consumption. Furthermore, the proposed Tb-TW-SPI metric, in this exploratory analysis, suggests potential for predicting postoperative pain, though this finding requires validation in larger cohorts with higher-frequency SPI sampling, offering a new direction for SPI interpretation. Large-scale, multicenter trials are warranted to validate the predictive utility of Tb-TW-SPI. Clinical Trial Registration, China Clinical Trial Registry: ChiCTR2400088444.

Humans

Strategies to improve recruitment to randomised trials.

BACKGROUND: Recruiting participants to randomised controlled trials (RCTs) is challenging. Identifying effective recruitment strategies would benefit health research: poor recruitment leads to underpowered trials, reducing the reliability of findings and increasing the risk of wasted resources, ethical concerns, and trial failure. Evidence to inform recruitment strategies is increasingly generated through Studies Within A Trial (SWATs), which are methodological studies embedded within host RCTs. This is an update of a review last published in 2018. OBJECTIVES: Primary: to quantify the effects of strategies to improve recruitment of participants to RCTs. Secondary: to evaluate recruitment strategies' cost-effectiveness and impact on retention, and the equity, diversity, and inclusion (EDI) characteristics of recruited participants. SEARCH METHODS: We used MEDLINE, Embase, and six other databases to identify the studies included in the review. We also sought unpublished recruitment SWATs through social media and targeted email dissemination to trial methodology networks. The latest search date was 16 February 2023. SELECTION CRITERIA: We included randomised SWATs evaluating trial recruitment strategies embedded in healthcare and non-healthcare trials. We excluded quasi-randomised, hypothetical, questionnaire-only, retention-only, or clinician incentive studies. DATA COLLECTION AND ANALYSIS: Primary outcome: proportion of eligible participants or centres recruited. SECONDARY OUTCOMES: cost-effectiveness, retention rates, and EDI characteristics of included participants. We conducted random-effects meta-analysis for strategies evaluated in at least two studies; otherwise, we synthesised results narratively. We reported effects as risk differences (RDs) with 95% confidence intervals (CIs), and assessed between-trial heterogeneity. We used GRADE to assess the certainty of evidence for the primary outcome. We expressed cost-effectiveness as the incremental cost per additional participant recruited in pounds sterling (GBP). MAIN RESULTS: We identified 91 eligible studies (53 new to this update), providing 94 comparisons and involving at least 176,747 participants. Eighty-one studies involved strategies aimed at trial participants, while 10 evaluated strategies aimed at recruiters. All were healthcare studies. We found 65 recruitment strategies; 49 were evaluated in a single study. Only five strategies were supported by high-certainty evidence according to GRADE criteria, and we focus on these strategies in the summary below. Open-label trials versus blinded, placebo trials. Open-label trials recruited more participants than blinded trials (RD 10%, 95% CI 8% to 12%; 3 studies, 9004 participants), corresponding to approximately 10 additional participants per 100 approached. The studies involved mostly women in the UK and Estonia. No cost or retention data were reported. Telephone reminder versus no telephone reminder. Telephone reminders to people who did not respond to an initial postal invitation boosted recruitment by 6% (95% CI 3% to 9%; 2 studies, 1450 participants), in trials with low underlying recruitment (we are less certain for trials with over 10% recruitment). The studies involved people with a mean age of 58 years in Canada and Norway. No cost or retention data were reported. Recruitment primer letter versus no letter. Pre-recruitment letters and leaflets designed to encourage participation made little or no difference to recruitment (absolute improvement 1%, 95% CI -1% to 2%; 2 studies, 5376 participants), and were associated with increased costs compared to not sending a primer (incremental cost: GBP 2.08). The studies involved mostly older white people in the UK and Ireland. Multimedia information via a digital link/QR code plus paper participant information leaflet (PIL) versus paper PIL alone. This made little or no difference to recruitment (absolute improvement 0%, 95% CI -1% to 1%; 7 studies, 11,612 participants) and retention (absolute improvement 0%, 95% CI -2% to 3%; 5 studies, 7403 participants), and increased costs compared to not including multimedia information (incremental cost: GBP 0.78). The studies involved people in the UK. Optimised, user-tested PIL versus standard PIL. Optimising participant information leaflets (e.g. through user-testing the leaflet with the target population to shape its content, format, and appearance) made little or no difference to recruitment: absolute improvement was 0% (95% CI 0% to 1%; 6 studies, 27,805 participants). The studies involved people in the UK. Only one study reported EDI data; participants were mostly older women. No cost or retention data were reported. We had moderate-certainty evidence for 13 other strategies; confidence was often reduced because the results came from single studies. Seven strategies involved changes to how potential participants received information; four involved changes to trial conduct; one targeted the recruiter or recruitment site; and one tested non-monetary incentives. We had much less confidence in the other 47 comparisons because the studies had design flaws, were single studies, or had very uncertain results. Costs were reported in only 17 of 91 studies. Strategy impact on retention was reported in 15 studies. All but one study (99%) were from high-income countries. The most reported demographics were age (49 studies), sex (32 studies), gender (27 studies), and education level (16 studies). AUTHORS' CONCLUSIONS: The evidence on strategies to improve trial recruitment remains broad but lacks depth. Of 65 strategies evaluated, only five were supported by high-certainty evidence. Open-label trial designs and telephone reminders to non-responders increased recruitment, while optimised participant information leaflets, recruitment primer letters, and multimedia information provided alongside a paper participant information leaflet had little or no effect. Reporting of participant characteristics was poor, limiting assessment of equity, diversity, and inclusion across most studies. Evidence is heavily skewed toward high-income countries. Future research must prioritise evaluations in low-to-middle-income settings and consistently report cost, retention, and EDI outcomes. We strongly urge the methodology research community to strengthen the evidence base by prioritising replications of existing strategies over the development and testing of new ones. FUNDING: National Institute for Health and Care Research (Advanced Fellowship, Adwoa Parker, reference:NIHR302256). Health Research Board, Republic of Ireland, Evidence Synthesis Ireland (grant ESI-2021-001) REGISTRATION: This review updates an earlier Cochrane review, which was first published in 2002 and subsequently updated in 2007, 2010, and 2018. Previous versions of the review and their protocols are available at: https://doi.org/10.1002/14651858.MR000013.pub2 https://doi.org/10.1002/14651858.MR000013.pub3 https://doi.org/10.1002/14651858.MR000013.pub4 https://doi.org/10.1002/14651858.MR000013.pub5 https://doi.org/10.1002/14651858.MR000013.pub6.

Randomized Controlled Trials as Topic

Outcomes of Stage IVA Cervical Cancer Treated with Radiation Therapy: A Systematic Review and Meta-Analysis.

FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant metastasis, is an uncommon but clinically challenging disease with limited high-quality evidence to guide management. We performed a systematic review and meta-analysis to evaluate survival outcomes, treatment-related morbidity, and prognostic factors in patients with stage IVA cervical cancer treated with definitive radiotherapy. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42024602426), PubMed, Embase, and Web of Science were searched through February 2025. Eleven studies comprising 492 patients met eligibility criteria. Pooled random-effects analyses demonstrated 2-, 3-, and 5-year disease-free survival rates of 41.5% (95% CI, 28.1-55.0), 34.2% (95% CI, 21.1-47.3), and 30.9% (95% CI, 16.0-45.8), respectively. Corresponding overall survival rates were 56.0% (95% CI, 46.2-65.9), 45.9% (95% CI, 35.9-55.9), and 34.8% (95% CI, 26.4-43.3). Weighted median disease-free survival and overall survival were 15.6 and 33.6 months, respectively. The pooled incidence of vesicovaginal or rectovaginal fistula was 23.7% (95% CI, 12.9-34.6). Adverse prognostic factors included pelvic nodal involvement, hydronephrosis, rectal invasion, omission of brachytherapy, and total EQD2 below 80-85 Gy. Concurrent chemoradiation and completion of brachytherapy were consistently associated with improved outcomes. Despite curative-intent treatment, long-term survival remains poor and treatment-related morbidity substantial. Durable pelvic control remains the principal therapeutic challenge. Concurrent chemoradiation with adequate-dose brachytherapy appears essential for optimal outcomes, while future stage IVA-specific studies incorporating image-guided adaptive brachytherapy, advanced radiotherapy techniques, and systemic treatment intensification are needed to improve survival and reduce treatment-related morbidity.

Humans

Analgesic effect of premixed nitrous oxide in postoperative rehabilitation for ankle fractures: a randomized controlled trial.

INTRODUCTION: The global incidence of ankle fractures is on the rise, effective postoperative rehabilitation is a crucial aspect of surgical management. However, the occurrence of severe pain during the rehabilitation continues to pose a substantial clinical challenge. METHODS: The study utilizes a dual-arm, single-center, double-blind, randomized controlled trial design. A total of 100 participants were enrolled. Participants included patients experiencing acute pain (self-reported pain score &#x2265;4) who underwent postoperative rehabilitation for ankle fractures. Participants undergoing rehabilitation training were randomized to receive either 65% nitrous oxide or 100% oxygen. The primary outcome measured was the pain score, while secondary outcomes encompassed anxiety scores, physiological indices, side effects, patient and therapist satisfaction, acceptance, and residual pain. RESULTS: Pain scores were found to be significantly lower in the nitrous oxide group than in the oxygen group (T1: median difference -3.0, [95% CI -3.4 to -2.6]; p&#x2009;<&#x2009;0.001; T2: median difference -2.0, [95% CI -2.8 to -1.2]; p&#x2009;<&#x2009;0.001). Compared with the oxygen group, both therapists (p&#x2009;<&#x2009;0.001) and participants (p&#x2009;<&#x2009;0.001) in the nitrous oxide group reported significantly higher satisfaction levels. Acceptance rate showed significant intergroup differences (p&#x2009;<&#x2009;0.001). No severe adverse effects were observed in either group. Anxiety scores between the two groups did not show a significant difference (p&#x2009;=&#x2009;0.31, &#x3b7;2 = 0.027). CONCLUSION: The safety and analgesic profile of nitrous oxide renders it a suitable option for pain management in postoperative ankle fractures rehabilitation, thus providing a safe and easily manageable alternative to the current available strategies. CLINICAL TRIAL REGISTRATION: We have registered at https://www.chictr.org.cn and the registration number is: ChiCTR2400089379.

Humans

Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review.

BACKGROUND: Stimulant use disorder (StUD), particularly involving cocaine and amphetamines, is associated with significant cognitive impairments that impede recovery and increase relapse risk. Atomoxetine, a selective norepinephrine reuptake inhibitor, has been proposed as a potential treatment given its role in enhancing executive function and its established efficacy in attention-deficit/hyperactivity disorder (ADHD). This systematic review aimed to evaluate the efficacy, cognitive, and mood effects of atomoxetine compared with placebo in individuals with StUD. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, and Embase databases was conducted to identify randomized controlled trials (RCTs) evaluating atomoxetine for StUD. Eligible studies compared atomoxetine with placebo and assessed outcomes related to cognition (attention and response inhibition), stimulant use or abstinence, mood symptoms, and safety. Data were extracted and synthesized qualitatively due to methodological heterogeneity across studies. RESULTS: Nine RCTs met the inclusion criteria. Findings on cognitive outcomes were inconsistent: Some studies reported improvements in attentional bias and inhibitory control, while others showed no significant effects. Atomoxetine did not significantly reduce stimulant use, craving, or sustain abstinence compared with placebo. Limited mood-related benefits were observed, particularly among male participants, although results were variable. Across studies, atomoxetine was well tolerated, with most adverse events mild and transient. CONCLUSION: Despite a compelling neurobiological rationale and evidence of modest cognitive and mood benefits, atomoxetine has not demonstrated consistent efficacy as a monotherapy for StUD. Its favorable safety profile may warrant further investigation in carefully defined populations, such as individuals with comorbid ADHD or in combination with behavioral interventions.

Atomoxetine Hydrochloride

The Impact of Hemoglobin Concentration on Prognosis in Patients With Diabetic Foot: A Systematic Review and Meta-Analysis of Risk Factors for Adverse Outcomes and Clinical Management.

BackgroundDiabetic foot (DF) complications, including diabetic foot ulcers (DFUs), lead to significant morbidity, disability, and economic burden. Hemoglobin (Hb) levels may influence the prognosis of DF patients, but their relationship with adverse clinical outcomes remains unclear. This systematic review and meta-analysis aimed to assess the association between hemoglobin concentration and the risk of adverse outcomes in diabetic foot patients, including amputation and mortality.MethodsWe followed PRISMA guidelines to conduct a systematic literature review. A meta-analysis was performed on observational studies assessing the impact of hemoglobin levels on amputation, mortality, and ulcer incidence. A random-effects model was applied, and risk bias was evaluated using the Newcastle-Ottawa Scale.ResultsA total of 22 observational studies involving 10,984 patients were included. Our meta-analysis revealed that lower hemoglobin levels were significantly associated with a higher risk of amputation (OR = 0.97, 95% CI: 0.94-0.99, P < .001), and lower hemoglobin concentrations were found in amputation cases compared to non-amputation cases (SMD = -0.14, 95% CI: -0.24 to -0.04, P < .01). However, no significant association was found between hemoglobin levels and mortality (OR = 0.99, 95% CI: 0.33-2.89, P > .05). Sensitivity and publication bias analyses indicated robust results.ConclusionLower hemoglobin levels were associated with higher odds of amputation in patients with diabetic foot. However, pooled effects were small and heterogeneity was substantial across studies; therefore, hemoglobin likely functions primarily as a marker of overall disease burden and perioperative risk rather than a proven modifiable target. Prospective interventional studies are needed to determine whether correcting anemia improves limb outcomes and survival.

Humans

Hypoxaemia and mortality in children with lower respiratory infection in low-income and middle-income countries: systematic review and meta-analysis.

BACKGROUND: Hypoxaemic lower respiratory infections (LRIs) are a leading cause of childhood mortality, with the highest burden in low-income and middle-income countries (LMICs). Hypoxaemia-low peripheral capillary oxyhaemoglobin saturation (SpO2)-is a marker of severity, and WHO recommends hospitalisation and oxygen administration for patients with SpO2 <90%. We aimed to update estimates from a 2015 systematic review and meta-analysis examining the association between hypoxaemia and mortality among children with LRIs in LMICs by incorporating studies published over the subsequent decade and evaluating mortality risk across multiple SpO2 thresholds. METHODS: We conducted a systematic review with meta-analysis by searching PubMed, Embase, LILACS, Global Index Medicus, Web of Science, and Scopus for peer-reviewed studies published between Jan 1, 2015, and June 18, 2025, with combined terms related to pneumonia, children, mortality, and LMICs. We also included selected earlier studies through citation checking. Eligible studies reported associations between hypoxaemia and mortality in children younger than 5 years with LRIs in LMICs. We excluded case reports and case series with fewer than five deaths, studies focused exclusively on the neonatal period, and those limited to children with specific comorbidities or to postoperative patients, for consistency with the original review. Two reviewers independently screened studies, extracted data, and assessed quality. Eligible studies were combined with those from the original review and analysed using random-effects models to estimate odds ratios (ORs) by hypoxaemia threshold subgroup. The protocol was registered on PROSPERO (CRD42023433946). FINDINGS: We identified 7734 records; 26 new studies met inclusion criteria and were combined with 18 from the original review. The 44 studies were published between 1993 and 2024 and were primarily from Africa (25 [57%] of 44) or Asia (19 [43%]); some studies spanned multiple locations. Data from 33 studies including 155&#x2009;633 participants were included in the primary meta-analysis. Hypoxaemia of any threshold was associated with higher odds of LRI mortality (OR 4&#xb7;36 [95% CI 3&#xb7;52-5&#xb7;39]) compared with no hypoxaemia. For SpO2 <90% versus 90-100%, OR for death was 4&#xb7;75 (95% CI 3&#xb7;42-6&#xb7;58). For SpO2 90-94% versus 95-100%, mortality risk was more than twice as high (OR 2&#xb7;27 [95% CI 1&#xb7;22-4&#xb7;25]). Heterogeneity was substantial (I2 64-85% across analyses), and eight (24%) of 33 studies in the primary meta-analysis had a high overall risk of bias; however, a sensitivity analysis restricted to studies with low or moderate risk of bias yielded similar results. INTERPRETATION: SpO2 <90% strongly predicts mortality in children with LRIs in LMICs. Children with SpO2 90-94% also have elevated risk, suggesting that paediatric LRI and pneumonia treatment algorithms should consider management at this hypoxaemia threshold. FUNDING: None.

Journal Article

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

Effect of transcutaneous vagus nerve stimulation in hemodialysis patients: A randomized controlled trial.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (tVNS) has shown potential in neurological, autoimmune, and cardiovascular disorders, but its effects on HD patients remain unclear. This study aimed to evaluate the efficacy and safety of tVNS in HD patients. METHODS: We conducted a randomized controlled clinical trial on patients receiving HD &#x2265;6&#x2009;months. The tVNS group received stimulation for 1&#x2009;h during the first 2&#x2009;h of HD sessions, three times weekly for 8&#x2009;weeks, while the control group received standard care. The primary outcomes were dialysis efficiency (Single-pool Kt/V, Sp Kt/V) and dialysis-related symptoms (Dialysis Symptom Index, DSI), assessed every 4&#x2009;weeks. Secondary outcomes included pain and fatigue scores, physical performance, Hemodialysis Comfort Scale, hemoglobin levels, Mini-Mental State Examination, and anxiety and depression scores, measured at baseline and 8&#x2009;weeks after intervention. RESULTS: A total of 63 patients were enrolled in the study, with 32 patients assigned to the tVNS group and 31 patients to the control group. At 8&#x2009;weeks, the tVNS group showed significant improvements in Sp Kt/V (1.31&#x2009;&#xb1;&#x2009;0.11 vs. 1.25&#x2009;&#xb1;&#x2009;0.10, p&#x2009;=&#x2009;0.02), and DSI (12.09&#x2009;&#xb1;&#x2009;5.84 vs. 16.26&#x2009;&#xb1;&#x2009;5.27, p&#x2009;=&#x2009;0.004), as well as reductions in pain and fatigue, and increases in physical function, comfort, and hemoglobin. However, there were no statistically significant changes observed in cognitive function, anxiety, or depression. CONCLUSIONS: tVNS could improve dialysis efficiency, symptoms, and physical function in HD patients, indicating it may have a role as a complementary therapy.

Humans