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Descemet Stripping Only in Fuchs Endothelial Corneal Dystrophy: Results of a Randomized Clinical Trial of Topical Ripasudil and Directions for Future Innovation.

PURPOSE: To review history of Descemet stripping only (DSO) in Fuchs endothelial corneal dystrophy, describe the results of a clinical trial of topical ripasudil after DSO (K-321-201 study), and discuss future directions. METHODS: A 1-year, phase 2, randomized, placebo-controlled multicenter clinical trial of two doses of K-321 (ripasudil) administered for 12 weeks after DSO surgery in Fuchs endothelial corneal dystrophy was performed. The primary endpoint, central corneal endothelial cell density (ECD) at 12 weeks after surgery, was determined by an independent reading center that was masked to study group assignment. Duration of corneal edema, need for medical or surgical rescue therapy, corneal thickness, and central ECD throughout the entire study period were also examined. Adverse events and exploratory endpoints were collected. RESULTS: Sixty-five subjects were enrolled (21 in the QID group, 22 in the BID, and in the placebo group). Over 95% of subjects completed the trial. The QID group had a higher central ECD 12 weeks after DSO than the placebo group (531 &#xb1; 312 cells/mm2 vs 228 &#xb1; 298 cells/mm2, P = .0065). Corneal edema cleared in 17/21 (81.0%) of the QID group at 12 weeks, compared with 2/22 (9.1%) of the placebo group (P < .0001). Rescue was required in 2/21 (9.5%) subjects in the QID group and 6/22 (27.3%) subjects in the placebo group (P = .0092). Adverse events were mild and did not lead to discontinuation of treatment. CONCLUSIONS: Topical K-321 given QID improves DSO outcomes, as demonstrated by a higher ECD, more rapid resolution of corneal edema, and reduced failure rate. The medication was well-tolerated.

Humans

Comparative Efficacy and Safety of Adjunctive 0.015% Triamcinolone Acetonide Topical Spray With Lokivetmab Versus Lokivetmab Monotherapy as 'Reactive Therapy' for Canine Atopic Dermatitis: A Randomised, Single-Blinded, Controlled Preliminary Trial.

BACKGROUND: Lokivetmab is considered an effective systemic therapy for dogs with atopic dermatitis (AD); however, utilisation of lokivetmab with adjunctive topical anti-inflammatory glucocorticoids has not been investigated in canine AD. OBJECTIVES: To evaluate the efficacy and safety of the combination therapy of lokivetmab and 0.015% triamcinolone acetonide (TCA) spray in dogs with AD. ANIMALS: Twenty dogs with nonseasonal AD. MATERIALS AND METHODS: This study was a randomised, single-blinded (investigators only) 4-week controlled trial. Dogs were randomised to receive lokivetmab monotherapy or lokivetmab-TCA spray per manufacturer instructions. Clinical assessments included the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04), CADESI-04E (i.e., extracted erythema grade alone) and the 10-grade pruritus Visual Analog Scale (PVAS10) at Day (D)0, D14 and D28. Complete blood count and serum biochemical analysis were performed on D0 and D28. RESULTS: The median CADESI-04 and CADESI-04E scores in the lokivetmab-TCA group were significantly reduced on D14 (p&#x2009;<&#x2009;0.05 for both) and D28 (p&#x2009;<&#x2009;0.01 for both) compared to baseline; there were no significant differences in lesional scores at any time point for the lokivetmab monotherapy group. Lokivetmab-TCA significantly reduced CADESI-04E values compared to the lokivetmab monotherapy group on D28 (p&#x2009;=&#x2009;0.04). Both interventions significantly reduced PVAS10 scores on D14 and D28 compared to D0 (p&#x2009;<&#x2009;0.05 for both groups). CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of TCA spray may be a useful and safe adjunctive therapy for systemic lokivetmab to alleviate pruritus and clinical lesions in the initial management of canine AD patients.

Animals

Effectiveness of Topical Huzhang Sanhuang with Standard Nursing for Chemotherapy-Induced Phlebitis: Randomized Controlled Study.

Chemotherapy-induced phlebitis (CIP) is a common complication of peripheral intravenous chemotherapy that can cause pain, local inflammation, treatment interruption, and diminished quality of life. This randomized controlled trial evaluated the efficacy and safety of the topical Huzhang Sanhuang (HZSH) formula, combined with standard nursing care, in managing CIP. Ninety-four hospitalized patients with CIP (grade I or higher) were randomly assigned in a 1:1 ratio to receive either topical HZSH formula plus standard nursing care (experimental group, n = 47) or 50% magnesium sulfate wet dressing plus standard nursing care (control group, n = 47) for 14 days. Prespecified outcomes included phlebitis grade, visual analog scale (VAS) pain score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), symptom resolution time, and safety indicators. By Day 14, patients in the experimental group demonstrated significantly greater improvement in phlebitis severity than those in the control group (risk ratio for grade &#x2265; II, 0.42; 95% confidence interval, 0.20-0.87; P = 0.012). The experimental group also showed significantly larger reductions in VAS pain scores, hs-CRP levels, and IL-6 concentrations (all P < 0.01). Kaplan-Meier analysis further demonstrated faster resolution of multiple local symptoms in the experimental group. Treatment adherence was high in both groups, and no serious adverse events or major safety concerns were observed. These findings indicate that the topical HZSH formula, combined with standard nursing care, is a safe and effective integrative nursing intervention that accelerates clinical recovery, alleviates local symptoms, and reduces the inflammatory burden in patients with chemotherapy-induced phlebitis.

Humans

Topical Carboxytherapy as an Adjunct to Skin Recovery Post-CO2 Laser Fractional Resurfacing.

BACKGROUND: Topical carboxytherapy, a transcutaneous carbon dioxide (CO2) delivery system, may support skin repair and regeneration, yet its role as an adjunct to fractional laser treatment remains underexplored. OBJECTIVE: To investigate the effectiveness and safety of topical CO2 mask (CO2Lift&reg; Carboxy Gel, Lumisque Skincare) in supporting skin recovery and improving clinical outcomes following fractional CO2 laser resurfacing. METHOD: This 12-week randomized, placebo-controlled trial evaluated mild-to-moderate photoaging (n=6 females only). Participants received either topical carboxytherapy (n=4) or standard care (n=2). Assessments included VISIA-CR imaging, biophysical measurements, investigator ratings, and paired (baseline and 4-week) skin biopsies. RESULTS: Topical carboxytherapy accelerated recovery and was well-tolerated, with no major adverse events. VISIA-CR imaging showed accelerated erythema resolution, transepidermal water loss normalized more rapidly, and pH remained stable. Skin histology at week 4 revealed epidermal thickening and rete ridge formation with topical carboxytherapy vs placebo. Investigator ratings demonstrated significantly improved healing, global assessment, and global aesthetic improvement scale scores, with trends toward improvement in photodamage, rhytides, and pigmentation. CONCLUSION: Adjunctive topical carboxytherapy after fractional CO2 resurfacing accelerated healing, improved barrier recovery, and overall aesthetic outcomes. Larger studies are needed to confirm these findings.

Humans

Interventions with a significant mortality difference in acute respiratory distress syndrome: A systematic review and comparison with Guidelines.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has a high mortality rate. European Society of Intensive Care Medicine (ESICM) and American Thoracic Society (ATS) Guidelines are the worldwide reference for clinicians in management of ARDS. Mortality represents one of the most important outcomes in intensive care practice and randomized controlled trials (RCTs) the highest level of evidence. We compared Guidelines recommendations with RCT results to highlight differences and find potential new therapeutic opportunities. METHODS: We performed a systematic review of all RCTs reporting a statistically significant mortality difference in ARDS and a subsequent comparison with ESICM and ATS Guidelines recommendations. RESULTS: We identified 33 RCTs and 23 interventions with mortality difference in ARDS patients. Seven interventions relate to invasive ventilation strategies, two to noninvasive ventilation strategies, one to extracorporeal membrane oxygenation (ECMO), 12 to drugs and one to nutritional support. In 25/33 (76%) RCTs the intervention was associated with mortality reduction and in 8/33 with mortality increase (24%). Multicenter studies were 24/33 (73%) while blinding was adopted in 19/33 (58%) studies. Guidelines recommendations supported by RCTs with mortality impact include: the use of low tidal volume ventilation, prone positioning, venovenous ECMO, steroids and the avoidance of high frequency oscillatory ventilation. Eight of the interventions identified were not mentioned by Guidelines but demonstrated reduced mortality, and five further interventions demonstrated increased mortality. CONCLUSIONS: This systematic review highlights potential gaps between RCTs results and Guidelines that could be used to plan future research or highlight topics to be discussed in future Guidelines.

Humans

Heterogeneity in Teriflunomide Treatment Arms: A Systematic Review and Meta&#x2011;Regression of Randomised Multiple Sclerosis Trials.

BACKGROUND: Teriflunomide is widely used as an active comparator in Phase 3 randomised trials for relapsing multiple sclerosis (RMS). Temporal changes in disease activity within teriflunomide-treated cohorts have not been systematically examined. OBJECTIVES: To assess temporal trends in relapse and disability outcomes across teriflunomide arms of Phase 3 multiple sclerosis (MS) trials and identify predictors of between-trial heterogeneity. METHODS: We performed a systematic review and meta-analysis of Phase 3 randomised controlled trials including a teriflunomide arm. PubMed, Scopus, and ClinicalTrials.gov were searched up to October 2025. Annualised relapse rate (ARR) and 12- and 24-week confirmed disability worsening (CDW) were extracted together with baseline characteristics. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses, meta-regression, and sensitivity analyses were performed. RESULTS: Twelve teriflunomide cohorts from eight trials involving 4,900 adults with RMS were included. ARR ranged from 0.11 to 0.37 with substantial heterogeneity (I2 = 94%). Trial start year was inversely associated with ARR and explained a large proportion of between-study variability in exploratory meta-regression analyses. Confirmed disability worsening outcomes also showed substantial heterogeneity with a weaker trend toward lower event rates in more recent trials. CONCLUSION: Teriflunomide-treated trial populations have shifted toward lower relapse activity over time, and trial start year was the principal predictor of between-trial heterogeneity in ARR in exploratory analyses. These findings most plausibly reflect evolving recruitment and diagnostic practices rather than changes in drug efficacy. Accounting for these temporal dynamics is essential when interpreting outcomes from RMS trial using teriflunomide as comparator.

Humans

Efficacy and safety of JAK inhibitors for vitiligo: an updated systematic review and meta-analysis of randomized controlled trials.

Purpose: Janus kinase (JAK) inhibitors are a promising therapeutic option for vitiligo, but previous meta-analyses have focused mainly on topical ruxolitinib versus placebo. Newer randomized controlled trials (RCTs) evaluating oral agents and head-to-head comparisons with active treatments have not been comprehensively synthesized. Materials and methods: We searched PubMed, Embase, the Cochrane Library, and Web of Science to 11 March 2026. Eligible RCTs evaluated JAK inhibitor monotherapy versus placebo or active comparators. Two reviewers screened records, extracted data, and assessed risk of bias using RoB 2.0. The primary outcome was F-VASI75. Meta-analyses used fixed-effect or random-effects models. GRADE assessed certainty of evidence. Results: Nine RCTs (1826 patients) were included. JAK inhibitors increased F-VASI75 versus placebo (RR 4.59, 95% CI 3.20-6.59; p&#xa0;<&#xa0;0.001). For F-VASI50, they were superior to tacrolimus (RR 1.88, 95% CI 1.02-3.45) but not significantly different from dexamethasone (RR 2.17, 95% CI 0.95-4.94). Serious adverse events were comparable between groups (RR 1.15, 95% CI 0.57-2.33). Evidence certainty was moderate. Conclusions: JAK inhibitors are effective and well tolerated for vitiligo. Topical ruxolitinib is supported as a first-line option for limited facial disease; oral agents show promise but require longer-term safety data.

Humans

Skin barrier repairing and anti-aging effects evaluation of a comprehensive topical regimen incorporating niacinamide, Pro-Xylane, and panthenol after PicoWay laser: a randomized controlled study.

Pro-Xylane is a potent anti-aging ingredient; however, there is limited knowledge regarding whether a comprehensive post-procedure regimen incorporating a combination of Pro-Xylane, niacinamide, and panthenol alongside other active agents can deliver synergistic benefits for both skin barrier repair and anti-aging. This study assesses the effectiveness of the REGENMEDIC cream (anti-aging cream) and REGENMEDIC serum (anti-aging serum) in promoting skin barrier recovery and enhancing anti-aging effects following PicoWay laser treatment. A 112-day randomized controlled trial was conducted with 88 Chinese females, who were divided into two groups: the test group, using REGENMEDIC cream and Serum following PicoWay laser treatment, and the control group, using standard care regimen consisting of a standard cream. Skin barrier-repairing effects were assessed during the initial 14 days following a single use of REGENMEDIC cream, while skin elasticity, firmness, wrinkles and skin tone were evaluated over the 112-day study period after the combined use of REGENMEDIC cream and Serum. The test group exhibited lower transepidermal water loss (TEWL) and higher hydration after 14 days compared to the control group, along with a more significant reduction in skin redness. After 112-day use of REGENMEDIC cream and serum, test group showed increased skin elasticity and firmness, reduced wrinkles, and an overall improvement in skin tone and texture. Dermatologists reported excellent tolerability, with minimal adverse events. Initial application of the REGENMEDIC cream facilitated rapid skin barrier repair, while the subsequent sequential regimen incorporating the serum yielded significant long-term anti-aging benefits following PicoWay laser treatment. This study demonstrates that targeting multiple physiological pathways-specifically hydration, barrier integrity, and cellular senescence-provides a robust therapeutic option for amplifying the anti-aging outcomes of aesthetic procedures.

Humans

Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p&#x2009;<&#x2009;0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2&#x2009;=&#x2009;50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

Humans

Effects of exercise on aerobic capacity in people with prehypertension or hypertension: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to quantify the effects of exercise on aerobic capacity in people with prehypertension or hypertension and to identify exercise prescription parameters that optimize improvements. A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and Scopus from inception to 24 October 2025. Data were pooled using standardized mean differences (SMDs) with 95% confidence intervals (CI). Fifteen studies met the inclusion criteria. Exercise significantly improved aerobic capacity in people with prehypertension or hypertension (SMD&#x200a;=&#x200a;0.88; 95% CI: 0.61-1.15; P &#x200a;<&#x200a;0.00001), with multicomponent training demonstrating superior efficacy. Exploratory subgroup analyses suggest that longer programs (&#x2265;12&#x200a;weeks), lower frequency (<3&#x200a;sessions/week), 60-min sessions or longer, total weekly exercise less than 180&#x200a;min, and professional supervision may be associated with better outcomes.

Humans

Determinants of Nonspecific Response to Treatment in Randomized Controlled Trials of Major Depressive Disorder: A Narrative Review.

The design, conduct, and interpretation of double-blind randomized placebo-controlled clinical trials in major depressive disorder (MDD) are complicated by determinants of nonspecific response to treatment (NSRT). This narrative review provides a comprehensive overview of the determinants of NSRT in randomized controlled trials (RCTs) for MDD, including the placebo effect, factors related to measurement of the primary endpoint, the inclusion of misdiagnosed patients, the relapsing-remitting course of MDD, and factors related to functional unblinding. Potential strategies to reduce the impact of the determinants of NSRT and to improve the interpretation of RCT outcomes in MDD are also summarized. These strategies include use of centralized rating and standardized rater training, independent diagnostic confirmation, optimized site selection, minimizing financial incentives, exclusion of subjects participating in multiple clinical trials, exclusion of patients with unstable major depressive episode trajectories, and use of active placebo and alternative trial designs. Uniformity among experts in the definitions of determinants of NSRT and related concepts, as well as in strategies to address them, may facilitate progress in the development of novel treatments for MDD.

Humans

Patient-reported outcomes in pediatric regional anesthesia trials: current use and limitations.

PURPOSE OF REVIEW: This review examines the current use and limitations of patient-reported outcome measures (PROMs) in pediatric regional anesthesia research. Despite the increasing emphasis on patient-centered outcomes, existing pediatric outcome assessment frameworks may inadequately capture the pain experience and interference with daily living. RECENT FINDINGS: Across 17 identified randomized controlled trials and 15 ongoing studies, PROM use remains highly variable, with consistent reliance on observational pain scales such as the Face, Legs, Activity, Cry, and Consolability scale and limited incorporation of standardized, longitudinal health-related quality-of-life measures. SUMMARY: Current pediatric PROM frameworks remain fragmented, limiting comprehensive evaluation of recovery. Greater standardization and incorporation of developmentally appropriate, longitudinal outcome measures are needed to better align clinical research with meaningful patient-centered endpoints and to improve assessment of functional and psychosocial recovery.

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

Virtual Reality Education for Hospitalized Pediatric Patients Improves Intrinsic Motivation: A Prospective, Randomized Crossover Study.

Hospitalized children experience educational disruption and reduced motivation during prolonged admissions. Despite the availability of in-hospital schools, many cannot participate due to illness severity or isolation precautions. This pragmatic, randomized crossover trial evaluated whether bedside virtual reality (VR) lessons improve intrinsic motivation among inpatients aged 5 to 25 years unable to attend the hospital school. Participants completed both VR-based educational sessions and standard of care (SOC) conditions on consecutive days. The primary outcome was intrinsic motivation, with secondary outcomes including educational self-efficacy, well-being, self-esteem, and parental experience. Of 156 enrolled patients, 100 were analyzed (mean age 11.5 [SD = 4.1 years]; 43.9% female). Intrinsic motivation scores were higher in the VR condition than SOC (P = .0048), and parental satisfaction was also greater (P = .0008). Bedside VR education represents a feasible, acceptable, and scalable adjunct to inpatient learning, supporting intrinsic motivation and caregiver satisfaction during hospitalization.Trial Registration: ClinicalTrials.gov NCT05725395, date first registered November 22, 2022.

Humans

Educational Effects of Electronic Documents and Videos on Parents' Responses to Acute Illness in Young Children: A Randomized Controlled Trial.

AIM: This study compared changes associated with electronic document-based and video-based education for parents responding to acute illness in young children, focusing on self-reported knowledge, anxiety, and satisfaction. METHODS: A randomized controlled trial with pre- and post-intervention measurements was conducted among 140 adults in Japan who self-reported raising a child under 3&#x2009;years of age and having experienced their child's acute illness. Participants were assigned to an electronic document group or a video group (n&#x2009;=&#x2009;70 each). Self-reported knowledge was assessed using a researcher-developed questionnaire, and anxiety was measured using the State-Trait Anxiety Inventory. Pre-post changes and between-group differences in change scores were examined. RESULTS: Total self-reported knowledge scores increased significantly in both groups (p&#x2009;<&#x2009;0.01), with no significant between-group difference. The video group showed significant improvements in items related to symptoms requiring attention at home and information sources, whereas the electronic document group improved in items related to symptoms requiring medical consultation and emergency calls. State and trait anxiety did not change significantly in either group. Satisfaction was high in both groups. CONCLUSIONS: Both educational formats may support parents' learning about responses to acute illness in young children, although appropriate formats may differ according to the educational content. Information provision alone may have limited effects on anxiety; therefore, future parent education should incorporate interactive and reassurance-focused approaches. TRIAL REGISTRATION: UMIN-CTR: UMIN000056457.

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

The effectiveness of protective behavioral strategies for reducing alcohol use and alcohol-related harms among adults: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Excessive alcohol consumption is a major public health concern. Protective behavioral strategies (PBS) are widely incorporated into alcohol interventions, but their effectiveness and role as mechanisms of behavior change remain unclear. This systematic review and meta-analysis evaluated the effects of PBS-based interventions on alcohol consumption, alcohol-related harms, and PBS use. METHODS: PubMed, Embase, Scopus, CINAHL, and ProQuest were searched from inception to December 2025 for randomized controlled trials (RCTs) of adults (&#x2265;18 years) delivering PBS as an active intervention component. Random-effects meta-analyses using Hedges' g examined alcohol quantity, drinking frequency, alcohol-related problems, and PBS use. RESULTS: Fifteen RCTs were included, predominantly involving young adults attending U.S. universities. PBS interventions increased protective strategy use (g=0.23, p=0.005 after outlier removal), but alcohol effects were modest: no change in quantity (g=-0.05, p=0.162), small reduction in frequency (g=-0.09, p=0.014), and marginal reduction in problems (g=-0.07, p=0.052; significant in sensitivity analysis). Subgroup findings suggested greater effects at longer follow-up and when PBS was incorporated into multi-component interventions. Evidence supporting PBS as a mechanism of change was limited and inconsistent. CONCLUSIONS: PBS-based interventions produce modest, context-dependent effects on alcohol outcomes. Most evidence comes from young U.S. university students, underscoring the need for studies in more diverse adult populations and further mechanistic research.

Humans

Closed-loop insulin delivery for glycaemic control in hospitalised and perioperative adults: A systematic review and meta-analysis of randomised controlled trials.

We evaluated whether closed-loop insulin delivery improves glycaemic control in hospitalised and perioperative adults. PubMed/MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to 29 June 2026 for randomised controlled trials comparing closed-loop or automated insulin delivery with usual care or conventional insulin therapy. Random-effects meta-analyses were conducted; risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. Seven trials involving 375 analysed participants were included. Closed-loop insulin delivery increased time in target glucose range by 23.91 percentage points (95% CI 19.40 to 28.43; I2&#xa0;=&#xa0;0%) and reduced mean glucose by 1.79&#xa0;mmol/L (95% CI 1.06 to 2.53 lower; I2&#xa0;=&#xa0;36.3%); certainty was moderate for both outcomes. Two trials involving 69 participants reported compatible participant-level data for clinically significant hyperglycaemia, and both estimates favoured closed-loop insulin delivery, although the evidence was exploratory and imprecise. No severe hypoglycaemic events occurred in either group, precluding reliable estimation of comparative safety. Closed-loop insulin delivery may improve glycaemic process measures, but larger pragmatic trials are needed to establish clinical benefits, safety, and implementation feasibility.

Humans