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PubMed2026

Frequent readmissions after hospitalization for alcohol withdrawal: a systematic review and meta-analysis.

BACKGROUND: Alcohol use disorder and alcohol withdrawal syndrome impose substantial clinical and economic burdens, with repeated hospitalizations being common. We aimed to systematically review readmission rates following inpatient detoxification, assess variation across study designs and hospital settings, and identify key risk and protective factors. METHODS: We performed a literature search in Embase and Pubmed on 10/04/2026 focusing on studies assessing in hospital alcohol detoxification. Exclusion criteria included studies on substance use other than alcohol and outpatient or residential treatment. Main outcome was rehospitalization, and meta-analysis was performed to estimate pooled readmission proportions. Secondary outcomes were risk factors and protective factors influencing the rate of rehospitalization. RESULTS: Twenty-five studies were included. The pooled proportion of readmissions following alcohol detoxification was estimated at 17% (95% CI: 14%-21%; 13 studies, n = 287,896) within 1 month, increasing to 44% (95% CI: 36%-52%; 8 studies, n = 2,877) at 1 year. Substantial between-study heterogeneity was observed. Subgroup analyses found no significant differences by hospital setting or time period. Findings for study aim and study design were mixed and based on limited data A small number of studies suggested associations with housing stability, employment, and treatment engagement. CONCLUSIONS: This meta-analysis suggests that approximately one in six patients are readmitted within 1 month and nearly half within 1 year after inpatient alcohol detoxification. However, readmission rates varied considerably across settings and populations. Future research should evaluate targeted interventions to reduce readmissions among high-risk patient groups.

Humans↗
PubMed2026

Reinforcement learning-based dynamic ensemble for missense variant effect prediction and tiered prioritization of VUS.

BACKGROUND: Accurate classification of missense variants remains a challenging task despite major advances in genomics. Numerous computational models have been developed to assist in variant classification, but often require repeated integration and benchmarking efforts. Ensemble methods have been proposed to overcome the limitations of single predictors, but mostly rely on fixed, predefined weights that constrain their ability to capture interactions among predictive signals. METHODS: We present GenixRL, a dynamic ensemble framework that reformulates model fusion as a reinforcement learning optimization problem. GenixRL uses a Q-learning agent to learn a policy that dynamically weights the probabilistic outputs of complementary predictors, including BayesDel (addAF and noAF), ClinPred, and MetaRNN. Replacing static weighting with policy learning allows GenixRL to adaptively identify optimal weightings and substantially improve classification accuracy. RESULTS: In benchmark evaluation against 25 state-of-the-art predictors, GenixRL achieved an AUROC of 0.9644 on an independent ClinVar dataset. On saturation genome editing assays for BRCA1 and BRCA2, GenixRL achieved the best performance and ranked highest on 14 of 17 clinically significant genes in a zero-shot evaluation. Applied to uncertain and conflicting ClinVar variants, GenixRL enabled tiered, evidence-based prioritization of hundreds of thousands of variants as likely pathogenic or pathogenic with high confidence, supported by orthogonal population evidence from gnomAD. CONCLUSION: GenixRL advances pathogenicity prediction for missense variants and provides an adaptive ensemble that sorts variants of uncertain significance into tiered candidates for expert curation and functional validation.

Mutation, Missense↗
PubMed2026

Association between prenatal exposure to tetrachloroethylene and adverse birth outcomes: Systematic review and meta-analysis.

BACKGROUND: Tetrachloroethylene (PCE) is a ubiquitous chlorinated solvent with documented placental transfer. Despite widespread environmental and occupational exposure, no prior systematic review has synthesized evidence on prenatal PCE exposure and adverse birth outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies. PubMed, Web of Science, PsycINFO, EMBASE, and CINAHL were searched from inception to July 13, 2026. Eligible studies reported associations between prenatal PCE exposure (drinking water or inhalation) and adverse birth outcomes. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) criteria. Random-effects meta-analyses were performed using risk ratios (RRs) with 95% confidence intervals (CIs), with Knapp-Hartung adjustments and Paule-Mandel τ2 estimation. RESULTS: Twenty one studies (1987-2023) met inclusion criteria. Prenatal PCE exposure was associated with spontaneous abortion (8 studies; RR = 1.28, 95% CI 1.00-1.63; I2 = 64.2%). Analyses of stillbirth, central nervous system defects, oral clefts, neural tube defects, preterm birth, low birthweight, and small-for-gestational-age (SGA) yielded positive but statistically non-significant pooled estimates. The certainty of evidence ranged from very low to low across outcomes (GRADE). CONCLUSIONS: Prenatal PCE exposure may be associated with spontaneous abortion, particularly at higher exposure levels, and with SGA. Findings support ongoing regulatory efforts to limit PCE in occupational and environmental settings, particularly for pregnant individuals. Future prospective studies with biological monitoring and confounder-adjusted designs are needed.

Tetrachloroethylene↗
PubMed2026

Antegrade dissection and re-entry vs retrograde strategy in chronic total occlusion percutaneous coronary intervention: Rationale and design of the ADRENALINE randomized study.

RATIONALE: While antegrade wiring (AW) is the most common initial strategy for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), difficult CTO lesions frequently require either antegrade dissection and re-entry (ADR) or a retrograde strategy. Comparative data between ADR and the retrograde approach remain limited. DESIGN: The Antegrade Dissection vs Retrograde re-ENtry And Load of Interventionalist Effort (ADRENALINE) is a prospective, multicenter randomized study with a superiority design. It is planned to enroll 121 patients with difficult coronary CTO (J-CTO score ≥2) referred for CTO-PCI in accordance with the hybrid algorithm. Subjects undergoing successful AW will be included in the observational arm. Patients with failed or unattempted AW will be randomized 1:1 to ADR or retrograde CTO crossing strategy (n = 74). All patients will undergo pre- and postprocedural laboratory testing (including cardiac troponin T and creatine kinase-MB), cardiac magnetic resonance (CMR) for late gadolinium enhancement, and health status assessment by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. The co-primary endpoints are total procedure time and successful guidewire crossing. Additionally, the relationship between different recanalization strategies and stress among interventional cardiologists will be explored. CONCLUSION: ADRENALINE is the first randomized study of ADR vs retrograde strategy for difficult CTO PCI, assessing procedural outcomes, CMR-detected myocardial infarction, and 3-month quality of life. ENROLMENT STATUS: The first patient was enrolled on July 29, 2025. As of June 14, 2026, 45 patients (26 randomized, 19 observational) of the planned 121 patients have been enrolled. TRIALS REGISTRATION: Clinicaltrials.gov: Identifier, NCT06878729.

Humans↗
PubMed2026

High-Flow Nasal Oxygen and the Risk of Gastric Insufflation: A Systematic Review and Meta-Analysis Supplemented by Narrative Synthesis.

High-flow nasal oxygen (HFNO) generates positive airway pressure, raising concerns about gastric insufflation and aspiration risk. Although most studies report minimal or no gastric distension, some suggest significant changes. This systematic review and meta-analysis applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to evaluate the effect of HFNO on gastric insufflation and related markers across clinical settings. We searched Medline, Embase, Emcare, and CINAHL through August 2025 for studies reporting qualitative or quantitative markers of gastric insufflation during HFNO use, including comet-tail artifacts, antral cross-sectional area, and gastric volume. Eligible designs included randomized trials, observational and volunteer studies, and case reports. Methodological quality was evaluated using the Mixed Methods Appraisal Tool, and certainty of evidence was rated with GRADE. Meta-analysis was performed for outcomes reported in two or more studies. Six randomized trials, five observational studies, two volunteer studies, one case series, and two case reports were included. Observational studies primarily assessed outcomes before and after HFNO intervention. Pooled analysis of four randomized controlled trials (RCTs; n = 375) showed HFNO significantly reduced gastric insufflation compared with face-mask ventilation during elective peri-intubation (risk ratios [RR] = 0.32; 95% confidence interval [CI], 0.19-0.52; P < .00001; I 2 = 0%), rated moderate-certainty. For antral cross-sectional area, pooled analysis of three RCTs (n = 318) found no significant difference between HFNO and face-mask ventilation (MD -0.33 cm 2 ; 95% CI, -0.72 to 0.05; P = .09; I 2 = 74%), rated moderate-certainty. Observational studies assessing pre- and post-HFNO changes showed no significant increase in antral cross-sectional area (MD 0.08 cm 2 ; 95% CI, -0.29 to 0.45; P = .67; I 2 = 0%) and no significant change in gastric liquid volume (MD -0.01 ml/kg; 95% CI, -0.07 to 0.06; P = .80; I 2 = 0%), both rated low certainty. Nonpooled data suggested possible increases in critically ill patients, but the evidence was of very low certainty. A single study assessing microaspiration found HFNO reduced gastroesophageal reflux and prevented microaspiration compared with face-mask ventilation. No clinically significant aspiration events were reported across studies. Moderate-certainty evidence supports HFNO as safe regarding gastric insufflation and antral cross-sectional area in most elective and procedural contexts. Low-certainty evidence suggests no increase in gastric volume. Caution is warranted due to limited, low-to-very-low-certainty evidence at higher flow rates and among critically ill patients. Larger multicenter trials and robust observational studies are necessary to confirm safety in these settings.

Humans↗
PubMed2026

The analgesic efficacy of intrathecal morphine compared to peripheral regional analgesia in total hip arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Following elective total hip arthroplasty, pain continues to be a significant problem. Intrathecal morphine or peripheral regional analgesia, that is local infiltration analgesia or peripheral nerve block, are common analgesic modalities, but it is still not known which is superior. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: The following electronic databases were searched from inception to 24 March 2026: CENTRAL; Ovid Embase; Ovid MEDLINE; Scopus; and Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials that compared intrathecal morphine to peripheral regional analgesia in patients scheduled for elective total hip arthroplasty under general or spinal anaesthesia. RESULTS: Eight trials and 471 patients were included. The peripheral regional analgesia was peripheral nerve block in six trials and local infiltration analgesia in two trials. No difference was demonstrated between intrathecal morphine and peripheral regional analgesia in regard to the first coprimary outcome, the pain score at rest at 24&#x200a;h. The quality of evidence was moderate. Intrathecal morphine was found to be superior to peripheral regional analgesia with respect to the second coprimary outcome, the cumulative intravenous morphine equivalent consumption at 24&#x200a;h. Mean difference (95% CI) was 11.38&#x200a;mg (4.31-18.45; P &#x200a;=&#x200a;0.002, I2 &#x200a;=&#x200a;81%). The quality of evidence was low. Intrathecal morphine was revealed to be superior to peripheral regional analgesia at 8-12&#x200a;h for the pain score at rest, 1.24 (0.60-1.88); P &#x200a;=&#x200a;0.0001, I2 &#x200a;=&#x200a;68%; pain score on movement, 1.15 (0.12-2.17), P &#x200a;=&#x200a;0.03, I2 &#x200a;=&#x200a;65%; but the rate of in hospital pruritus was reduced with peripheral regional analgesia, 0.31 (0.17-0.58), P &#x200a;=&#x200a;0.0002, I2 &#x200a;=&#x200a;0%. No differences in functional status were shown. CONCLUSIONS: We found no difference between intrathecal morphine and peripheral regional analgesia in regard to pain score at rest at 24 h. Intrathecal morphine may lead to a favourable effect on some but not all analgesic indices compared to peripheral regional analgesia in elective total hip arthroplasty. The quality of evidence for these positive effects was low. Intrathecal morphine reduced the systemic opioid consumption, but is not in itself an opioid free strategy. This notion is supported by the increased incidence of in hospital pruritus with intrathecal morphine. The quality of evidence for this was high. In view of the quality of evidence, high quality randomised controlled trials are required to substantiate these results.

Humans↗
PubMed2026

Preregistration nursing student attrition and strategies to improve student retention in university; an umbrella review.

BACKGROUND: Attrition among preregistration nursing students remains a persistent international challenge, contributing to nursing workforce shortages. Although extensive research has examined factors influencing student attrition and retention, the evidence is fragmented across review-level literature, limiting clarity regarding priority and evidence-informed retention strategies. AIM: To synthesize review-level evidence on factors associated with preregistration nursing student attrition and to identify strategies that support student retention in university-based nursing programs. METHODS: An umbrella review was conducted in accordance with the Joanna Briggs Institute methodology. Six electronic databases were systematically searched for peer-reviewed literature reviews published in English between January 2016 and October 2025. Eligible reviews focused on undergraduate preregistration nursing students in face-to-face university programs. Methodological quality was appraised using the JBI critical appraisal checklist. Findings were synthesised using narrative and thematic approaches. RESULTS: Seventeen literature reviews were included. Attrition was consistently described as multifactorial, influenced by academic preparedness, psychosocial wellbeing, socio-demographic factors, and institutional support. Retention strategies reported across reviews were predominantly relational, developmental, and sustained over time, including mentoring, tutoring, academic skills development, psychosocial support, and interventions that foster belonging. Faculty engagement and holistic approaches were repeatedly associated with improved student persistence. However, the evidence base was largely descriptive, with limited experimental evaluation of intervention effectiveness. CONCLUSION: Preregistration nursing student retention is best supported through multifaceted, sustained strategies that begin at admission and extend throughout the curriculum. While current evidence highlights consistent patterns of effective support, further rigorous research is required to evaluate retention interventions and extend evidence to flexible nursing education pathways.

Humans↗
PubMed2026

The psychosocial supports and interventions accessed by family members of patients with developmental and epileptic encephalopathies: A systematic review.

AIM: Family members of patients with developmental and epileptic encephalopathies (DEEs) face profound emotional, social and practical challenges, yet little is known about how they access psychosocial support. We synthesised the literature on the psychosocial support accessed by family members of patients with DEEs, including evidence-based interventions. METHOD: Four databases were searched. Two reviewers independently screened and extracted data, appraised study quality (QualSyst Tool), and determined certainty of evidence (GRADE-CERQual Framework). Data were synthesised using inductive thematic analysis. RESULTS: 28 papers comprising 27 unique studies were included and methodological quality was high overall (median&#xa0;=&#xa0;0.91, IQR&#xa0;=&#xa0;0.85-1.00). Most studies focused on parent experiences; only two included siblings' perspectives. Families reported high psychological needs which were rarely met by psychological support. Clinicians rarely provided adequate information, quality communication or addressed mental health. Families valued respite care, but experienced barriers to access. Peer support was the most common and valued resource. Three studies tested interventions and appeared feasible and acceptable for parents. However, evidence for intervention effectiveness is preliminary and limited to small, uncontrolled pilot studies. INTERPRETATION: Gaps exist in psychosocial support provision for families of patients with DEEs, including insufficient research on siblings' and grandparents' needs, and lack of evidence-based interventions. We propose evidence-informed research and implementation strategies to address these gaps.

Humans↗
PubMed2026

The impact of artificial intelligence on critical thinking and clinical reasoning in health professions education: A systematic review and meta-analysis.

BACKGROUND: Critical thinking and clinical reasoning underpin healthcare professionals' ability to navigate uncertainties and deliver safe and effective care. With artificial intelligence (AI) advancement and growing adoption, AI-based educational tools are increasingly used to support these cognitive competencies' development. OBJECTIVE: To synthesize randomised and controlled clinical trials on AI-based educational tools in health professions education and examine their effects on critical thinking and clinical reasoning among health professions students. METHODS: Six electronic databases were searched from January 1, 2014 to July 28, 2025 was reviewed: PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, Embase and Web of Science. Two independent reviewers performed data extraction and quality assessment using standardized JBI checklists. The GRADE approach was used to assess the certainty of evidence. Studies were pooled via random-effects meta-analyses or narrative syntheses. RESULTS: Fourteen randomised controlled trials and seven controlled clinical trials were included (n&#xa0;=&#xa0;21). Meta-analyses revealed small to medium effect sizes for the surrogate clinical reasoning outcomes of performance-based assessment scores (SMD 0.68; 95% CI [0.38, 0.98], p-value&#xa0;=&#xa0;0.00; I2&#xa0;=&#xa0;38%) and knowledge test scores (SMD 0.39; 95% CI [0.09, 0.69], p-value&#xa0;=&#xa0;0.01; I2&#xa0;=&#xa0;79%). Critical thinking and clinical reasoning skills and dispositions were narratively synthesized, with majority of included studies favouring AI-based interventions but the evidence had low to very low certainty. CONCLUSION: AI-based educational interventions may improve critical thinking and clinical reasoning among health profession students, but the evidence is very uncertain. This review offers preliminary insights but does not allow identification of optimal interventions or discipline-specific recommendations due to small sample sizes and substantial intervention heterogeneity. Further research is required to draw definitive conclusions. PROTOCOL REGISTRATION: CRD42025634074.

Humans↗
PubMed2026

Same-day initiation of tenofovir alafenamide-based pre-exposure prophylaxis with drug-level feedback for transgender women in Uganda.

OBJECTIVE: To evaluate the feasibility and acceptability of same-day initiation of emtricitabine/tenofovir alafenamide (F/TAF) pre-exposure prophylaxis (PrEP) and test the impact of drug-level feedback on PrEP adherence among transgender women (TGW) in Uganda. DESIGN: Randomized controlled trial. METHODS: HIV-negative TGW were randomly assigned 1&#x200a;:&#x200a;1 to intervention (drug-level feedback with tailored adherence counseling) or standard-of-care (SOC), and followed quarterly for 12&#x200a;months (November 2021-July 2023; NCT04491422). Quarterly clinic visits included demographic and socio-behavioral data collection, PrEP refills, STI testing, and quarterly PrEP adherence assessment using tenofovir levels in dried blood spots (DBS; long-term) and urine (short-term). RESULTS: We enrolled 200 TGW (100 per arm), median age 21&#x200a;years. Same-day F/TAF PrEP initiation was 100%. Tenofovir detection in urine (intervention arm) was 79, 80, 85, and 70% at the 3, 6, 9, and 12-month visits, respectively. Tenofovir detection in DBS was 46, 40, 35, and 31% at 3, 6, 9, and 12 months, respectively. Median tenofovir DBS concentrations were 40.6 and 47.0&#x200a;fmol/punch in intervention and SOC arms, respectively. There was no intervention effect on PrEP adherence (DBS tenofovir levels) [adjusted incidence rate ratio (aIRR) 1.06; 95% CI: 0.82-1.37]. Never being harassed by police for being transgender (aIRR 1.66; 95% CI: 1.24-2.23), history of taking daily medication for more than 7&#x200a;days (aIRR 1.51; 95% CI: 1.18-1.93) and higher monthly income (aIRR 1.44; 95% CI: 1.10-2.04) were associated with PrEP adherence. CONCLUSION: Oral F/TAF PrEP adherence among TGW in Uganda was low and not affected by drug-level feedback or tailored adherence counseling. Long-acting injectable PrEP formulations should be considered for this population.

Humans↗
PubMed2026

A single session of high-definition transcranial direct current stimulation does not modulate effects of knee two-point discrimination training or sensorimotor function in healthy adults: Double-blind randomised controlled trial.

BACKGROUND: Benefits of sensory-training interventions on sensorimotor outcomes are inconsistent, and it is unclear whether transcranial direct current stimulation (tDCS) can enhance proprioception, which is fundamental to neuromuscular control. Existing evidence is dominated by upper-limb studies, so transferability to the knee is unclear. This study investigated whether a single session of anodal high-definition (HD)-tDCS, alone or combined with brief two-point discrimination (TPD) training, enhances knee sensorimotor function and performance in healthy adults. METHODS: In a double-blind randomised-controlled trial, 57 healthy participants received (1) 20-min, 1&#xa0;mA anodal HD-tDCS over the knee primary somatosensory (S1) map or sham stimulation, and (2) 15-min knee TPD training or no training. Knee somatosensory, sensorimotor, and functional performance measures were assessed pre- and immediately post-intervention. Three-way mixed-design ANOVAs, equivalence testing (smallest effect size of interest &#x3b7;2&#xa0;=&#xa0;0.02), Bayes factors, and linear mixed-effects models quantified effects. RESULTS: HD-tDCS, TPD training, and their sequential combination had no effect on any outcome measure (p&#xa0;&#x2265;&#xa0;0.05; &#x3b7;2&#xa0;&#x2264;&#xa0;0.015). Confidence intervals spanned equivalence bounds, and equivalence testing results were non-significant (p&#xa0;&#x2265;&#xa0;0.05). Bayes factors (<0.33) showed moderate evidence for the null (no effect). Mixed-effects modelling attributed &#x2264;8% of total variance to intervention fixed effects, with the remainder captured by participant-level random effects. CONCLUSION: A single 20-minute session of 1&#xa0;mA HD-tDCS, with or without brief TPD training, does not acutely modify knee somatosensory, sensorimotor, or functional performance in healthy adults. Existing evidence at the hand may not translate to the lower limb. Future work should investigate higher-dose, multi-session, task-concurrent, or network-targeted strategies in clinical populations.

Humans↗
PubMed2026

Symptom Networks and Core Symptoms in Patients with Solid Tumors Undergoing Chemotherapy: A Systematic Review.

OBJECTIVES: To summarize symptom network characteristics in patients with solid tumors undergoing chemotherapy and synthesize evidence on core symptoms, bridge symptoms, and temporal associations. METHODS: We systematically searched eight databases through October 2025 to identify studies that applied symptom network analysis to adults with solid tumors receiving chemotherapy. Eligible studies assessed symptoms using cross-sectional, longitudinal, or interventional designs. Two reviewers independently screened articles and extracted data on study characteristics, symptom assessment, and network outcomes. Methodological quality was assessed using the National Institutes of Health Study Quality Assessment Tool. RESULTS: Twenty-seven studies involving 13,452 participants were included, yielding 79 symptom networks. Fatigue was the most frequently identified core symptom (10/20, 50%), whereas sadness, lack of appetite, and nausea each occurred in 10% of studies, with variation across cancer types, treatment phases, and latent classes. Bridge symptoms included disturbed sleep, lack of appetite, and dry mouth (2/7, 28.6%). Studies evaluating temporal associations found that symptoms such as sadness, dyspnea, somnolence, and dry mouth predicted subsequent changes in appetite, distress, nausea, and other outcomes. Strength metrics showed acceptable stability (correlation stability coefficients: 0.28-0.83). CONCLUSIONS: Fatigue was frequently identified as a central symptom across studies, largely reflecting evidence from breast cancer studies. Core symptoms varied across cancer types, treatment phases, and latent classes, suggesting heterogeneity. IMPLICATIONS FOR NURSING PRACTICE: These findings highlight the importance of considering relationships among symptoms in clinical care. Focusing on key symptoms such as fatigue, while tailoring management strategies to cancer-specific symptom patterns, may support more effective symptom management.

Humans↗
PubMed2026

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD&#xa0;=&#xa0;-0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD&#xa0;=&#xa0;-0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans↗
PubMed2026

Umbilical Cord-Derived Cell-Based Interventions for Bronchopulmonary Dysplasia and Related Complications in Preterm Infants: A Bayesian Sparse-Data Meta-Analysis.

Bronchopulmonary dysplasia (BPD) is a major complication of prematurity with limited disease-modifying therapies. We evaluated umbilical cord-derived cell-based interventions for BPD and related complications in preterm infants. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-based systematic review and meta-analysis were registered in PROSPERO. PubMed, Cochrane Library, Web of Science, CNKI, and Wanfang were searched from inception to June 14, 2026. Comparative clinical studies of umbilical cord-derived cell-based interventions in preterm infants at risk of or diagnosed with BPD were included. Outcomes included BPD, BPD severity, death, persistent pulmonary hypertension of the newborn (PPHN), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), late-onset sepsis (LOS), and adverse events (AEs). Bayesian random-effects meta-analysis used a binomial-normal hierarchical model to estimate pooled odds ratios (ORs), 95% credible intervals (CrIs), prediction intervals, and heterogeneity. Twelve studies were included. Umbilical cord-derived cell-based interventions showed a possible protective effect on overall BPD (OR, 0.48; 95% CrI, 0.14-1.20). Stronger associations were observed for severe BPD (OR, 0.17; 95% CrI, 0.01-0.85), moderate or severe BPD (OR, 0.28; 95% CrI, 0.09-0.70), and ROP stage &#x2265;3 (OR, 0.17; 95% CrI, 0.02-0.65). No conclusive benefit or harm was observed for death, PPHN, PDA, IVH, NEC, or LOS. No treatment-related serious AEs were identified. However, prediction intervals were generally wide, and the certainty of evidence was low to very low for most outcomes. Umbilical cord-derived cell-based interventions may reduce the risk of moderate or severe BPD in preterm infants, with an additional potential benefit for ROP stage &#x2265;3. Current evidence remains limited, and larger randomized trials with standardized outcomes and long-term follow-up are needed.

Humans↗
PubMed2026

Intervention components, training dose, and adherence in exercise-based prevention of hamstring strain injury in football: a systematic review and meta-analysis.

OBJECTIVE: To quantify associations between exercise-based prevention programmes and hamstring strain injury (HSI) risk in football participants, and whether training dose and adherence modify effects. METHODS: Six databases were searched to 1 October 2025. Randomised and cluster-randomised trials comparing HSI prevention programmes with usual practice or warm-up in football participants were included. Random-effects meta-analysis pooled risk ratios (RRs); subgroup analyses and meta-regression assessed effect modification. RESULTS: Fifteen trials (n = 7,465) were analysed. Programmes reduced HSI risk (RR = 0.51, 95% CI 0.36-0.71), with I&#xb2;=57% and a prediction interval crossing the null (0.18-1.40). Based on a control event rate of 7.8%, absolute risk reduction was 3.8% (38 fewer HSIs per 1000 participants; 95% CI 23-50 fewer). Effects were stronger for shorter interventions (1-6 months; RR = 0.43) than longer interventions (7-10 months; RR = 0.77; P for interaction=0.04), and for elite/semi-professional players (RR = 0.38) than amateur players (RR = 0.77; P for interaction = 0.02). Training frequency and weekly volume did not modify effects, whereas adherence did. High adherence (&#x2265;75%) was associated with lower HSI risk (RR = 0.36, 95% CI 0.28-0.48), whereas low adherence (<75%) showed no clear benefit (RR = 0.92, 95% CI 0.68-1.23; P for interaction <0.00001). Each 10% increase in adherence corresponded to an RR multiplier of 0.83 (approximately 17% lower RR). Certainty of evidence was low. CONCLUSION: Exercise-based programmes reduce HSI risk in football when implementation supports sustained adherence. Effects may be stronger in shorter interventions and elite populations, but evidence remains insufficient to differentiate programme types or components.

Humans↗
PubMed2026

Systematic Review of Pharmacologic Treatment for Migraine Prevention in Adults: Report of the AAN Guidelines Subcommittee and the American Headache Society.

BACKGROUND AND OBJECTIVES: This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS: A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, &#x2265;50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS: A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION: This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

Humans↗
PubMed2026

The Impact of Upper Extremity Rehabilitation on Fatigue in Individuals With Multiple Sclerosis: A Systematic Review.

BACKGROUND: Although numerous interventions have been investigated to alleviate fatigue in people with multiple sclerosis (PwMS), evidence regarding the effects of upper extremity rehabilitation on fatigue remains limited. OBJECTIVE: The objective of this review was to evaluate and synthesize the available evidence on the effects of upper extremity rehabilitation interventions on fatigue in PwMS. METHODS: This review was conducted in accordance with the PRISMA guidelines and was prospectively registered in the PROSPERO database. A systematic search of PubMed, Web of Science, and Scopus was performed up to August 2026. Studies were eligible if they investigated the effects of upper extremity rehabilitation interventions on fatigue in PwMS. The risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 (RoB 2), and the certainty of the evidence was appraised using the GRADE methodology. RESULTS: Nine studies including 250 participants (136 intervention, 114 control) met the inclusion criteria. The included studies evaluated a range of technology-assisted, exercise-based, home-based, and task-oriented upper extremity rehabilitation approaches, with some interventions incorporating more than one therapeutic or technological component. Fatigue outcomes were measured using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Risk of bias was low in three randomized controlled trials, with some concerns in two and high in two; among the two crossover studies, one was rated as low risk and one as high risk. GRADE assessment showed low certainty of evidence for studies using the FSS and very low certainty for those using the MFIS, indicating an overall low certainty of the available evidence. CONCLUSIONS: The available evidence is insufficient to draw definitive conclusions regarding the effects of upper extremity rehabilitation on fatigue in PwMS. Further high-quality randomized controlled trials are required.

Humans↗
PubMed2026

Effectiveness of an educational video for caregivers of children with neurogenic bladder: A randomized controlled trial.

BACKGROUND: The complexity of neurogenic bladder (NGB) management underscores the importance of caregiver education, yet high-quality education materials remain scarce. This study aims to assess the effectiveness and acceptability of an educational video designed to improve knowledge about NGB among caregivers of children with this condition. METHODS: We identified English-speaking caregivers of patients aged zero to 18 years, diagnosed with NGB, without prior major bladder reconstructive surgery, who received care at our institution from 2018 to 2022. Caregivers were randomly assigned into control or video groups using a block randomization model based on age. The control arm completed a six-item knowledge assessment before viewing the video, while the video group watched the video first. All participants rated the video's acceptability. Qualitative analysis of the open-ended responses to the acceptability questionnaire followed principles of thematic analysis. RESULTS: Of 409 eligible participants, 106 (25.9%) completed the study. Video (n = 48) and control (n = 58) groups were demographically similar. In the video group, 64.6% answered correctly all questions in the knowledge questionnaire, compared to 31% in the control group. After adjusting for patient age, caregivers in the video group were more likely to answer any question in the knowledge assessment correctly (relative probability: 1.13, 95% CI [1.06, 1.21], p < 0.01). Evidence for a difference in correct response rate among individual questions was strongest for question #1, which asked about common urological conditions for which NGB patients are at higher risk (95.8% vs. 79.3%, p = 0.01), and question #6, which asked about indications for bladder surgery (87.5% vs. 67.2%, p = 0.01), with the video group more likely to answer correctly for both questions. Qualitative analysis identified three major themes regarding parents' acceptance of the educational video: 1) attitudes towards video content and presentation, 2) usefulness of video as an educational tool, and 3) future directions. CONCLUSIONS: Our study found that an educational video about NGB effectively enhanced parental understanding of the condition and was deemed acceptable by parents as an introductory educational tool. The literature shows the benefit of using technology and visual aids to enhance health literacy for patients and caregivers, a key first step towards optimizing health outcomes for pediatric urologic patients.

Humans↗