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PubMed2026

Evaluation of the clinical and mechanistic role of MCM2 expression in the prediction of meningioma recurrence after radiotherapy.

OBJECTIVE: Postoperative radiotherapy is an effective treatment for meningiomas; however, treatment response varies among patients. In addition, practical methods for predicting tumor recurrence after radiotherapy have not been well established. Minichromosome maintenance protein 2 (MCM2), a key regulator of DNA replication licensing, was recently implicated in highly proliferative molecular subtypes of meningioma. In this study, the authors evaluated whether MCM2 immunohistochemical expression predicts response to radiotherapy in patients with meningiomas. METHODS: The authors retrospectively analyzed the records of patients with WHO grade 1-3 meningiomas treated with resection followed by radiotherapy at a single institution between July 2003 and November 2023. The MCM2 labeling index was assessed immunohistochemically, and patients were stratified into MCM2-high and -low groups using a cutoff of 35%. Progression-free survival (PFS) was defined as the interval from the completion of radiation therapy to postoperative radiological tumor recurrence or regrowth. Patients who showed no progression were censored at their last follow-up. PFS was estimated using Kaplan-Meier analysis and subsequently evaluated with Cox proportional hazards models. To further investigate the biological mechanisms associated with MCM2 expression, comprehensive transcriptomic analyses, including gene set enrichment analysis, was performed to elucidate the molecular processes that occur within MCM2-high tumors. RESULTS: The study population included 15 men (42%) and 21 women (58%), with a mean age of 63 years. Ten tumors (28%) were classified as MCM2-high meningiomas and 26 (72%) as MCM2-low meningiomas. High MCM2 expression was significantly associated with WHO grades 2-3 histology and higher Ki-67 labeling indices. During a median follow-up of 2.52 years, tumor progression after radiotherapy occurred in 47% of the patients. High MCM2 expression (HR 8.34, p = 0.03) was significantly associated with shorter PFS and remained an independent predictor of recurrence after adjustment for WHO grade, tumor size, and Ki-67 labeling index. Transcriptomic analyses of MCM2-high tumors revealed upregulation of cell proliferation-related pathways, accompanied by increased signaling through the E2F8-CHEK1 axis associated with radiation resistance and suppression of the TNF-α signaling pathway implicated in radiosensitivity. CONCLUSIONS: In meningiomas, high MCM2 expression is associated with early recurrence following radiotherapy. The study findings suggest that this association is driven by diverse biological mechanisms related to cell cycle regulation and radioresistance. Immunohistochemical assessment of MCM2 expression may serve as a practical and accessible biomarker for risk stratification and may support the future development of individualized postoperative radiotherapy strategies.

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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

Unraveling the Clinical Spectrum of DNASE1L3 Deficiency: Insights from Case Series and Systematic Literature Review.

BACKGROUND: DNASE1L3 deficiency is a rare monogenic cause of lupus and lupus-like autoimmunity resulting from impaired extracellular DNA clearance and sustained immune activation. Although most reported patients present with early-onset systemic lupus erythematosus (SLE), emerging evidence suggests broader phenotypic variability, including vasculitic and overlap manifestations. Whether these presentations represent distinct clinical entities or a continuum of DNASE1L3-associated immune dysregulation remains unclear. We aimed to define the clinical spectrum of DNASE1L3 deficiency and examine the relationship between recurrent pathogenic variants and disease severity. METHODS: We conducted a combined pediatric case series and systematic literature review. Four children with genetically confirmed biallelic DNASE1L3 variants followed at a tertiary pediatric rheumatology centre were retrospectively analysed for clinical, immunological, genetic, treatment, and outcome data. In parallel, a systematic search of PubMed/MEDLINE, Scopus, and Web of Science identified previously reported patients with confirmed biallelic pathogenic or likely pathogenic DNASE1L3 variants and extractable patient-level clinical data. To facilitate cross-case comparison, we applied an exploratory three-tier descriptive framework reflecting increasing disease severity: vasculitic or organ-limited disease (G1), systemic lupus or overlap phenotypes without irreversible organ damage (G2), and severe systemic organ-damaging disease (G3). The assigned grades were descriptive rather than permanent categories, as some patients may meet the criteria for a higher grade if broader systemic manifestations or irreversible organ damage develop during follow-up. FINDINGS: Fifteen reports provided extractable patient-level data, corresponding to 45 unique previously reported patients after accounting for known or probable overlapping reports. Combined with four patients from our centre, the analysis included 49 genetically confirmed individuals. SLE-dominant disease was the most frequent phenotype (27 [60%] of 45), followed by hypocomplementaemic urticarial vasculitis/HUVS-dominant disease (10 [22.2%]) and overlap phenotypes (8 [17.8%]). Renal involvement was reported in 30 (66.7%) of 45 patients, and disease onset occurred by age 3 years in 20 (44.4%). Persistent hypocomplementemia affecting C3 and C4 was frequently reported across the spectrum. Recurrent DNASE1L3 variants were observed across multiple phenotypic and severity grades. Variants such as p.Asn191Ser and p.Thr97Ilefs*2 occurred in patients spanning organ-limited vasculitic disease, lupus overlap phenotypes, and severe multisystem lupus with major organ involvement. CONCLUSION: DNASE1L3 deficiency was associated with a broad clinical spectrum of immune-mediated disease rather than a single clinicopathological entity. The occurrence of identical pathogenic variants across distinct phenotypic and severity states argues against a simple genotype-phenotype model and suggests that additional modifiers influence disease expression.

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PubMed2026

Isometric Exercises for Tendinopathies: A Systematic Literature Review.

PURPOSE: Musculoskeletal disorders are among the most common reasons for medical consultation, with tendinopathies accounting for up to 30% of such presentations. Although exercise remains the cornerstone of management, the most effective modality continues to be debated. Eccentric exercise has long been the mainstay, but the role of isometric exercise in pain modulation and functional recovery remains unclear. This systematic review aims to evaluate the current evidence on the efficacy of isometric exercises in the management of tendinopathies across various anatomic sites. METHODS: A systematic search was conducted in PubMed, MEDLINE, Embase, and the Cochrane Library from inception to August 1, 2025. Eligible studies included randomized controlled trials and prospective or retrospective cohort studies assessing isometric exercise interventions for tendinopathy, with or without comparator groups. Case series and case reports were excluded. Data extracted included participant demographic characteristics, site of tendinopathy, symptom duration, treatment duration, adherence, and outcome measures such as Victorian Institute of Sports Assessment (A, P, or G), visual analog scale, Patient-Specific Functional Scale, 36 item short form health survey (SF-36), and EuroQol 5-Dimension questionnaires. Imaging outcomes (ultrasound or magnetic resonance imaging) were recorded where available. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias tool in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. FINDINGS: The search identified 304 articles, of which 13 randomized controlled trials met the inclusion criteria, encompassing 336 participants (40% female). Tendinopathy sites included the patellar (n = 4), Achilles (n = 3), lateral elbow (n = 2), rotator cuff (n = 2), wrist extensor (n = 1), and gluteal (n = 1) tendons. Median symptom duration was 23 months (interquartile range, 3-51 months). Intervention periods ranged from a single 45-minute session to 4-month exercise programs. Treatment adherence was high initially (nearly 100%) but declined over time, with 70% of participants in the isometric and 58% in the control (isotonic) groups completing ≥80% of sessions. Pain reduction and functional improvement were statistically significant in only 3 studies. Imaging-based outcomes were inconsistently reported, and study heterogeneity precluded meta-analysis. Overall methodological quality was rated as good in 3 studies and poor in 10. IMPLICATIONS: Current evidence provides limited support for the superiority of isometric exercise in tendinopathy management. Although isometric regimens appear tolerable and may confer short-term analgesic benefits, their long-term efficacy relative to eccentric or isotonic protocols remains uncertain. Future research should prioritize standardized outcome measures, longer follow-up, and uniform diagnostic criteria to strengthen the evidence base for exercise prescription in tendinopathies.

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PubMed2026

Adverse Experiences in Brief Meditation Practices: Randomized Controlled Trial.

BACKGROUND: Meditation has become increasingly popular in recent decades. However, relatively little remains known about the prevalence of and risk factors for adverse experiences related to a single meditation practice. OBJECTIVE: The objective of our study was to examine adverse experiences associated with 3 brief, digitally delivered meditation practices (mindfulness, self-compassion, and gratitude) relative to using the internet as usual, as well as to investigate whether preintervention characteristics could predict such outcomes. METHODS: In a secondary analysis of a randomized controlled trial using samples that were representative of the US and UK adult populations with regard to ethnicity, sex, and age, we examined adverse experiences associated with 3 brief (ie, 5 or 10 minutes) meditation practices (ie, mindfulness, self-compassion, and gratitude) relative to using the internet as usual. We also investigated the potential of using preintervention characteristics to predict such outcomes. RESULTS: A total of 5049 participants completed all preintervention measures and were randomly assigned to meditation or control conditions. Across the sample, 4.1% (204/4925) of participants reported having a distressing experience during the intervention, and 7.1% (348/4908) of participants experienced an increase in negative affect from before to after the intervention. The results showed that participants who were randomized to a brief meditation intervention were no more likely to report a distressing experience than those who were randomized to use the internet as usual (odds ratio [OR] 1.05, 95% CI 0.76-1.47; P=.76). The results also showed that participants who were randomized to a brief meditation intervention were less likely to report clinically relevant increases in negative affect relative to using the internet as usual (OR 0.63, 95% CI 0.50-0.80; P<.001). Notably, participants in the 10-minute condition had a significantly higher likelihood of reporting a distressing experience than those in the 5-minute condition (OR 1.42, 95% CI 1.07-1.89; P=.02). Preintervention characteristics showed acceptable discrimination ability to predict a distressing experience (area under the curve=0.73) and slightly lower ability to predict increased negative affect (area under the curve=0.67). CONCLUSIONS: Taken together, we found that the brief, digitally delivered meditation practices tested in this study carry risks of adverse experiences that are comparable to or lower than those of typical activities on the internet; 10-minute condition was more likely to result in distressing experiences than 5-minute condition; and adverse responses to a brief meditation practice can, at least to a certain degree, be predicted using preintervention characteristics. TRIAL REGISTRATION: Open Science Framework 94HKS; https://osf.io/94hks/overview.

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PubMed2026

Adeno-Associated Virus Gene Therapy Translation: Lessons from Early Regulatory Meetings.

The Platform Vector-Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative that aims to develop adeno-associated virus (AAV) gene therapies for four monogenic rare diseases, two organic acidemias and two congenital myasthenic syndromes. PaVe-GT's platform-based approach identifies and diminishes redundancies and applies efficiencies in preclinical, clinical, and regulatory activities. The program's hypothesis is that implementing these efficiencies can accelerate clinical trial initiation. Based on its platform-centric experience and public-serving mission, the PaVe-GT program actively shares its scientific and regulatory learnings with the public to benefit the development of similar gene therapy products for rare diseases. PaVe-GT's first investigational AAV gene therapy candidate is AAV serotype 9 human propionyl-CoA carboxylase alpha subunit (AAV9-hPCCA) for propionic acidemia caused by PCCA deficiency, which received initial feedback from the Food and Drug Administration (FDA) in an INitial Targeted Engagement for Regulatory Advice on CBER/Center for Drug Evaluation and Research (CDER) ProducTs (INTERACT) meeting. Upon further product development that took into consideration the FDA's initial advice, the program obtained the Agency's feedback in pre-investigational new drug (IND) (Type B) and Type C meetings. Here, we share our experience from these meetings, including strategy, preparation, pre- and post-meeting feedback from the FDA, and lessons learned during the AAV9-hPCCA regulatory process, which the program plans to apply across the PaVe-GT platform. Topics discussed in the regulatory meetings included animal model and efficacy studies, toxicology study plans, manufacturing of the investigational AAV product, and clinical trial design. The main lessons learned from the pre-IND and Type C meetings for AAV9-hPCCA are: (1) Pharmacology/Toxicology studies in a single rodent species are sufficient for filing an initial IND; (2) FDA feedback guides product quality improvements and early development of a quantitative potency assay; (3) use of biomarkers as potential surrogate endpoints in a future efficacy trial benefits from collection of data in the natural history study and the first-in-human Phase 1/2 study; and (4) evidence from the Phase 1/2 clinical trial could be leveraged to support a license application. Lightly redacted regulatory documents and comprehensive templates developed by the PaVe-GT team are available on the PaVe-GT website.

Dependovirus↗

PubMed2026

Second-Generation ELZA-sub400 Protocol: Individualized High-Fluence Cross-Linking for Ultra-Thin Keratoconus Corneas.

PURPOSE: To evaluate the safety and efficacy of a second-generation individualized corneal cross-linking (CXL) protocol (ELZA-sub400) using high-fluence UV-A irradiation in ultrathin ectatic corneas. DESIGN: Retrospective, single-center, consecutive interventional case series. METHODS: Twenty-nine eyes of 24 patients with progressive keratoconus or post-LASIK ectasia and a post-soak intraoperative thinnest stromal thickness <400 µm were included. After epithelial removal and riboflavin soaking, continuous UV-A irradiation (365 nm) at 3 or 9 mW/cm² was delivered with total fluence titrated up to 10 J/cm² based on intraoperative ultrasound pachymetry and a previously published nomogram targeting an uncross-linked stromal margin of approximately 70 µm above the endothelium. Outcomes were assessed at baseline and up to 12 months using corrected distance visual acuity (CDVA) and corneal parameters measured using Scheimpflug tomography and anterior segment OCT (AS-OCT) with Placido-based topography. The main outcome measure was the proportion of eyes without progression at 12 months, defined as <1.0 D increase in maximum keratometry (Kmax). Secondary outcomes included changes in CDVA, refraction, Kmax, stromal thickness, demarcation line depth, densitometry, and safety parameters. RESULTS: At 12 months, 22/29 eyes (76%; 95% CI, 57.9%-87.8%) met the nonprogression criterion. Mean change in Kmax was -0.77 ± 5.10 D (95% CI, -2.71 to 1.17; P = .418). Mean demarcation line-to-anterior stroma distance was 205 ± 64 µm (95% CI, 180.7-229.3), and demarcation line-to-endothelium distance was 64 µm (IQR, 49-152). All demarcation lines remained within the stromal layer; 15/29 eyes (51.7%) had a demarcation line located ≤70 µm from the endothelium. Median CDVA changed from 0.10 to 0.32 logMAR (P = .142). Minimum stromal thickness showed a median change of -4.0 µm (P = .309). No significant change was observed in densitometry, and no eye developed deep stromal haze or endothelial decompensation. CONCLUSIONS: Second-generation ELZA-sub400 CXL halted ectasia progression in 76% of ultrathin corneas at 12 months and was associated with an acceptable short-term safety profile, including stromal-confined demarcation line formation and no observed endothelial decompensation. The numerical decline in spectacle CDVA observed in this severely affected cohort did not reach statistical significance but is clinically important and warrants confirmation in larger prospective studies.

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PubMed2026

Spinal meningiomas: histopathological grading using a benchmark radiomics model with notes on disease control.

OBJECTIVE: Spinal meningiomas (SMs) are common primary spinal tumors for which surgery is considered the first-line treatment when safe and feasible. The ability to extrapolate the tumor grade from preoperative imaging may significantly inform early patient expectation-setting regarding recurrence. Building on radiomics studies in cranial meningiomas, the authors aimed to construct a benchmark radiomics model to preoperatively identify the histological grade of SMs. METHODS: Institutional surgical records from May 2012 to November 2025 were queried for pathology-confirmed meningiomas below the foramen magnum, with preoperative contrast-enhanced imaging available for segmentation. SMs were classified as low-grade (WHO grade 1) and high-grade (WHO grade 2 tumors and grade 1 tumors with atypia). Tumors were manually segmented, and features were extracted using the PyRadiomics software package. An ensemble model of k-nearest neighbors, random forest, and support vector machine classifiers was trained using nested cross-validation on a subset of 10 features to differentiate tumor grades. Clinical data for the cohort were also extracted, and disease control in an adjunctive clinical series was assessed. RESULTS: Seventy-four patients were included in radiomics analysis, with an area under the receiver operating characteristic curve of 0.879 and a mean F1 score of 0.748. The model's top 5 features were all texture features that differed significantly (p < 0.05) across low- and high-grade SMs. These included measures of tumor textural and contrast-enhancement heterogeneity, with overlap with features reported in radiomics models for histological grading of intracranial meningiomas. Fifty-five patients with a median radiographic follow-up of 22.2 (range 1.9-86.4) months remained for clinical analysis after exclusion of patients with less than 1 month of follow-up and syndromic meningiomas. Four recurrences occurred at a median of 20.8 (range 1.8-41.8) months. High-grade tumor pathology did not significantly impact progression-free survival (p = 0.682, log-rank test; Cox regression high vs low grade hazard ratio [HR] 0.62, 95% CI 0.06-6.11, p = 0.685). Subtotal resection was associated with poorer progression-free survival than gross-total resection (p = 0.004, log-rank test; Cox regression subtotal vs gross-total resection HR 10.62, 95% CI 1.46-77.05, p = 0.019). These findings remain contextualized within a relatively limited follow-up window and small recurrence event count, suggesting a need to characterize the interplay between tumor grade and extent of resection as drivers of local disease control in SMs. CONCLUSIONS: A preoperative radiomics model can stratify high-grade SMs using open-source tools applied to single-institution data.

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PubMed2026

Ultra-high-frequency ECG quantifies residual electrical dyssynchrony during left bundle branch area pacing in patients with wide QRS: a paired within-patient study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may restore a more physiological pattern of ventricular activation in patients with conduction delay; however, QRS narrowing alone may incompletely characterize electrical resynchronization. Ultra-high-frequency ECG (UHF-ECG) provides quantitative markers of ventricular activation timing and dyssynchrony. OBJECTIVE: To quantify paired OFF-to-ON changes in conventional ECG and UHF-ECG metrics during LBBAP in patients with baseline wide QRS and to assess the relationship between paced R-wave peak time (RWPT) and residual UHF-ECG dyssynchrony. METHODS: In this prospective single-center paired study, 21 patients with bradycardia and baseline wide QRS underwent standard ECG and UHF-ECG assessment during intrinsic rhythm (pacing OFF) and during LBBAP (pacing ON). Endpoints included QRS duration, signed VED16, absolute VED16 (|VED16|), mean ventricular delay (meanVD), and a clinically interpretable distance-to-normal metric defined as dist = max(|VED16|-20, 0). Paired changes were summarized as medians with bootstrap 95% confidence intervals and tested using the Wilcoxon signed-rank test. Associations between paced RWPT and residual dyssynchrony during pacing were evaluated using Pearson and Spearman correlation coefficients. RESULTS: LBBAP significantly narrowed QRS duration from 136.8 [130.2-153.6] ms during intrinsic rhythm to 116.0 [107.8-125.6] ms during pacing (median Δ -21.0 ms; 95% CI -33.9 to -18.6; p < 0.001). Signed VED16 did not change significantly (median Δ 0.4 ms; p = 1.000), consistent with the mixed conduction-phenotype composition of the cohort. In contrast, severity-oriented UHF-ECG endpoints improved: |VED16| decreased numerically (median Δ -5.2 ms; p = 0.070), whereas dist decreased significantly (median Δ -0.7 ms; 95% CI -14.4 to 0.0; p = 0.015). The proportion of patients within the normal dyssynchrony band (|VED16| ≤ 20 ms) increased from 7/21 (33.3%) to 12/21 (57.1%). Median paced RWPT was 66.6 [58.6-74.6] ms, and shorter RWPT correlated with lower residual |VED16| during pacing (Pearson r = -0.45, p = 0.038). CONCLUSIONS: In patients with baseline wide QRS, LBBAP produces marked QRS narrowing, whereas UHF-ECG provides complementary quantification of residual electrical dyssynchrony. Severity-oriented UHF-ECG endpoints, particularly a distance-to-normal metric, may offer an interpretable mechanistic framework beyond conventional ECG alone. Shorter paced RWPT was associated with lower residual dyssynchrony during pacing, supporting physiological coherence between procedural and high-resolution electrocardiographic markers.

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PubMed2026

Cardiorespiratory training for people with stroke.

RATIONALE: Low levels of cardiorespiratory fitness are common after stroke and are associated with post-stroke disability and increased risk of secondary stroke. Cardiorespiratory training interventions aim to increase cardiorespiratory fitness, improve physical function, reduce disability, and help prevent future strokes. Clinical guidelines recommend exercise as part of lifestyle modification for secondary prevention, and strongly recommend exercise for rehabilitation. This review is one of three reviews that were originally a single review on physical fitness training for stroke. OBJECTIVES: The primary objective of this review was to determine whether cardiorespiratory training after stroke has an effect on death, disability, adverse events, risk factors, fitness, walking, and indices of physical function when compared to a non-exercise control. SEARCH METHODS: In April 2025, we searched nine bibliographic databases and two trials registers to identify studies for inclusion in the review. We checked reference lists, tracked citations, and contacted experts. ELIGIBILITY CRITERIA: We included randomised controlled trials comparing cardiorespiratory training interventions with usual care, no intervention, or a non-exercise intervention in people with stroke. OUTCOMES: Our critical outcomes were death, disability, adverse events, risk factors, fitness, walking, and indices of physical function, assessed at the end of the intervention and the end of the longest follow-up. RISK OF BIAS: We used the Cochrane RoB 1 tool to assess the risk of bias in the included studies. SYNTHESIS METHODS: The studies evaluated different comparisons (e.g. cardiorespiratory training versus no intervention/waiting list control or versus attention control or versus usual care), which we synthesised into a single comparison: cardiorespiratory training versus control. We used random-effects meta-analysis on arm-level data (risk difference (RD) for dichotomous data, and mean difference (MD) or standardised mean difference (SMD) for continuous data, with 95% confidence intervals (CIs)). For outcome data that we did not meta-analyse, we followed Synthesis Without Meta-analysis (SWiM) guidance. We used GRADE to assess the certainty of the evidence for critical outcomes. INCLUDED STUDIES: We included 53 studies (2672 participants, with an average age of 61.9 years). Most studies recruited ambulatory participants in the early subacute (7 days to 3 months) or chronic (> 6 months) phases of recovery. Exercise duration recommendations were met in 49 studies, and frequency recommendations in 48. Twenty-eight studies lacked balanced exposure between groups. Programme duration was 12 weeks or more in 16 studies (maximum: 24 weeks). Sixteen studies had a post-intervention follow-up period (12 weeks to 12 months from baseline). One study planned a six-month follow-up but did not report it. SYNTHESIS OF RESULTS: Cardiorespiratory training does not increase or decrease deaths at the end of intervention (RD 0.00, 95% CI -0.01 to 0.01; 36 studies, 1563 participants; high-certainty evidence) or the end of follow-up (RD -0.00, 95% CI -0.02 to 0.02; 10 studies, 713 participants; high-certainty evidence). Cardiorespiratory training may improve indices of disability slightly at the end of intervention (SMD 0.35, 95% CI 0.12 to 0.57; 17 studies, 1073 participants; very low-certainty evidence), but the evidence is very uncertain. Re-expressed using the Barthel Index (0 to 20), the equivalent effect is MD 1.68, 95% CI 0.59 to 2.74. It is unclear if the effect is clinically meaningful (the minimal clinically important difference (MCID) is +1.85). The effect is unclear at the end of follow-up (SMD -0.14, 95% CI -0.36 to 0.08; 5 studies, 347 participants; low-certainty evidence). Cardiorespiratory training does not increase or decrease the incidence of secondary cardiovascular or cerebrovascular events at the end of intervention (RD -0.00, 95% CI -0.03 to 0.02; 8 studies, 544 participants; high-certainty evidence) and probably does not affect them at the end of follow-up (RD -0.02, 95% CI -0.08 to 0.04; 4 studies, 412 participants; moderate-certainty evidence). It is very uncertain whether cardiorespiratory training affects systolic blood pressure (mmHg) at the end of intervention (MD -2.12, 95% CI -5.81 to 1.57; 9 studies, 535 participants; very low-certainty evidence) (MCID -2 mmHg) or follow-up (MD 0.93, 95% CI -4.30 to 6.16; 3 studies, 155 participants; very low-certainty evidence); the 95% CIs include the MCID. Cardiorespiratory training probably results in a slight improvement in cardiorespiratory fitness (VO2 ml/kg/min) at the end of intervention (MD 2.37, 95% CI 1.39 to 3.36; 13 studies, 608 participants; moderate-certainty evidence); it is unclear if the effect is clinically meaningful (MCID +3.5 ml/kg/min). The effect may be similar at the end of follow-up (MD 2.76, 95% CI 1.36 to 4.16; 5 studies, 237 participants; low-certainty evidence). Subgroup analysis favoured longer interventions. Cardiorespiratory training probably results in a slight increase in comfortable walking speed (metres per second) at the end of intervention (MD 0.08, 95% CI 0.04 to 0.12; 16 studies, 647 participants; moderate-certainty evidence), but the effect is not clinically meaningful (MCID +0.13). The effect is unclear at the end of follow-up (MD 0.02, 95% CI -0.05 to 0.10; 3 studies, 182 participants; low-certainty evidence). Cardiorespiratory training may improve indices of balance at the end of intervention (SMD 0.31, 95% CI 0.15 to 0.47; 18 studies, 772 participants; very low-certainty evidence), but the evidence is very uncertain. Re-expressing using the Berg Balance Scale, the equivalent effect is MD 2.09, 95% CI 1.10 to 3.07; and it is unclear if it is clinically meaningful (MCID of +2). The effect is unclear at the end of follow-up (MD 0.90, 95% CI -1.32 to 3.12; 6 studies, 253 participants; low-certainty evidence). Overall, our certainty about the evidence is limited for most outcomes by imprecision (small number of studies and participants) or risks of bias (e.g. imbalanced exposure doses) or both. AUTHORS' CONCLUSIONS: Cardiorespiratory training after stroke does not affect mortality or the incidence of secondary events at the end of the aerobic exercise training programme or end of follow-up. It may increase fitness, reduce disability, increase walking speed, and improve balance at the end of intervention, but it is unclear if these improvements are clinically meaningful. Further well-designed randomised trials are needed to fully understand the potential benefits and long-term effects of cardiorespiratory training and the optimal exercise prescription. FUNDING: No dedicated funding REGISTRATION: Protocol (and previous versions) available via DOI 10.1002/14651858.CD003316.

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PubMed2026

Clinical outcomes of zirconia dental restorations: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the survival and success rates of zirconia dental restorations (ZDRs) and their complications. DATA & SOURCES: Electronic searches of PubMed, Cochrane, Embase and Web of Science were conducted up to January 1, 2026. Clinical studies with at least 1-year follow-up evaluating zirconia dental restorations in natural teeth were included. Survival rates, success rates, and biological and mechanical complications were analyzed. Risk of bias was assessed using RoB 2, Newcastle-Ottawa Scale (NOS), and Joanna Briggs Institute tools (JBI). Certainty of evidence was evaluated using the GRADE approach. STUDY SELECTION & RESULTS: Sixty-six studies published between 2008 and 2025 were included. Pooled survival rates ranged from 92.9% to 98.7% up to 10 years for single crowns (SCs), 77.6% over 10 to 13 years for fixed dental prostheses (FPDs), 97.4% for resin-bonded FPDs (RBFPDs) over 10 to 15 years, from 50.0% to 52.6% over 9 to 13 years for conventional cantilever FPDs (CFPDs) and 89.0% for inlay-retained FPDs (IRFPDs) over 10 years. Pooled success rates were 46.1% for SCs over 10 years, 40.1% for FDPs over 10 to 13 years, 84.3% for RBDPDs over 10 to 15 years, 12.5% to 22.6% for CFPDs over 9 to 13 years and 70.3% for IRFPDs over 10 years. Biological and mechanical complication rates were 12.1% and 53.9% for SCs at 10 years, 19.4% and 46.7% for FPDs over 10 to 13 years, 50.0% and 37.5% for CFPDs at 9 years, 21.4% and 14.3% for IRFPDs at 3 years, and 3.3% and 8.0% for RBFPDs over 10 to 15 years. Restorations treated with airborne-particle abrasion (APA) combined with 10-methacryloyloxydecyl dihydrogen phosphate (MDP) achieved favorable short-term clinical outcomes, with pooled survival and success rates of 98.6% and 97.7% for SCs, and 98.1% and 70.1% for IRFPDs, respectively. The included studies were assessed as having low to moderate risk of bias using RoB 2, NOS, and JBI tools, but GRADE assessment yielded evidence of very low certainty. CONCLUSIONS: ZDRs generally demonstrated acceptable to excellent short- to long-term survival and success outcomes. Mid- to long-term clinical performance was varied according to restoration types. The RBFPDs had relatively low complication rates, followed by the SCs, the FPDs and the IRFPDs. CFPDs exhibited relatively low success rates and high complication rates. The predominant biological complications were secondary caries and pulpitis or apical periodontitis, while chipping and debonding were the most common mechanical complications. APA treatment followed by application of MDP is capable of producing favorable short-term clinical outcomes. CLINICAL SIGNIFICANCE: ZDRs except for CFPDs could achieve favorable mid- to long-term clinical performance. CFPDs should be conducted with caution.

Zirconium↗

PubMed2026

Daridorexant in severe obstructive sleep apnea: effects on sleep-disordered breathing and sleep.

STUDY OBJECTIVES: To evaluate the effect of daridorexant on nighttime respiratory function and sleep in adults with severe obstructive sleep apnea (OSA) without insomnia. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, two-period, crossover trial was conducted at a single sleep center in 16 adults (≥18 years) with severe OSA without insomnia. In each period, daridorexant 50 mg or placebo was administered every evening for 5 days. Primary and secondary endpoints were the treatment differences (daridorexant-placebo) for apnea/hypopnea index (AHI) and oxygen saturation (SpO2) during total sleep time (TST), respectively, after last dosing. A mean increase in AHI ≥10 events/h and mean decrease in nocturnal SpO2 ≤-2% were the minimum changes considered to be clinically meaningful negative effects. Other endpoints included TST, latency to persistent sleep (LPS), and wake after sleep onset (WASO). RESULTS: Mean baseline AHI was 51.2 events/h (range 30.8, 82.2) and mean SpO2 during TST was 92.1% (range 88.5, 94.3). No clinically meaningful effect of daridorexant on AHI or SpO2 during TST was detected. Treatment differences were -3.7 events/h (one-sided 95% CI ≤ +4.2) and - 0.12 % (one-sided 95% CI ≥ -0.6), respectively. Compared with placebo, daridorexant increased TST by 32.5 min (90% CI: 6.9, 58.2), associated with shorter LPS (-10.3 min [90% CI: -20.6, -0.02]) and a trend towards reduced WASO (-15.2 min [-31.2, 0.9]). Four adverse events were reported (daridorexant n = 3; placebo n = 1), all of mild intensity and none related to respiratory function. CONCLUSION: Short-term treatment with daridorexant does not impair sleep-disordered breathing and may improve sleep in patients with severe OSA. CLINICAL TRIAL: ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT05458193, NCT05458193. Statement of Significance Obstructive sleep apnea (OSA) is highly prevalent and associated, in 30%-50% of cases, with insomnia-related symptoms, yet the safety of insomnia medications in OSA remains unclear. Daridorexant, a dual orexin receptor antagonist for the treatment of adults with insomnia disorder, previously showed no negative effect on sleep-disordered breathing in participants with mild/moderate OSA. This randomized, double-blind, placebo-controlled, crossover trial evaluates daridorexant 50 mg (maximum therapeutic dose) in participants with severe OSA without insomnia. Repeated dosing (5 nights) did not impair nighttime respiratory function, as assessed by apnea/hypopnea index and nocturnal oxygen saturation. Moreover, improvements in sleep characteristics were observed with daridorexant, extending evidence that daridorexant 50 mg is safe and well-tolerated and may improve sleep in adults with severe OSA.

Humans↗

PubMed2026

Longitudinal functional trajectory and surgical outcomes after intracranial meningioma resection: implications for surgical decision-making in older patients.

OBJECTIVE: As the population ages, meningiomas are increasingly encountered in older patients, yet longitudinal functional outcomes following surgery across age groups remain incompletely characterized. This study evaluated age-related differences in clinical and tumor characteristics, functional trajectory, and surgical outcomes. METHODS: This was a retrospective cohort study of 396 consecutive patients who underwent surgery for intracranial meningiomas at a single academic center between January 2023 and September 2025. Patients were stratified into 5 age groups (< 65, 65-69, 70-74, 75-79, and ≥ 80 years). Neurological deficits and Karnofsky Performance Status (KPS) were assessed preoperatively, at discharge, and at last follow-up. Logistic regression analyses identified predictors of prolonged length of stay (LOS) (> 5 days) and poor functional outcome at discharge (KPS < 80). RESULTS: Older patients presented with greater comorbidity burden, larger tumors, and lower preoperative KPS (all p < 0.05), while gross-total resection was achieved at comparable rates across all age groups (p = 0.504). A clinically meaningful inflection point was observed around age 75 years, with KPS < 80 at discharge rising from 7.4% and 9.7% in the < 65-year and 70- to 74-year subgroups and to 36.2% and 57.1% in the 75- to 79-year and ≥ 80-year subgroups (p < 0.001), and median LOS increased from 4 days in the younger groups to 9 and 7 days in the 75- to 79-year and ≥ 80-year groups (p < 0.001). However, recovery rates among patients who experienced functional decline at discharge were comparable across age strata. On multivariable analysis, independent predictors of prolonged LOS were age ≥ 75 years (OR 2.31, p = 0.019), diabetes mellitus (OR 2.85, p = 0.004), posterior fossa location (OR 2.1, p = 0.008), tumor diameter (OR 1.33, p < 0.001), postoperative edema (OR 2.58, p = 0.015), and neurosurgical complications (OR 3.18, p = 0.002). Independent predictors of poor functional outcome at discharge were age ≥ 75 years (OR 5.84, p < 0.001), lower preoperative KPS (OR 2.8, p < 0.001), posterior fossa location (OR 3.72, p = 0.003), neurosurgical complications (OR 3.56, p = 0.008), and recurrent meningioma (OR 2.89, p = 0.025). Among 70 endoscopic endonasal approach patients, higher preoperative deficit burden and subtotal resection rates were observed compared to open craniotomy, though overall functional outcomes were comparable. CONCLUSIONS: Surgical risk in meningioma resection increases from age 75 years onwards, yet recovery capacity following initial functional decline remains similar across all age groups. Preoperative functional status, tumor location, comorbidity burden, and recurrence history should guide surgical decision-making rather than age alone.

Humans↗

PubMed2026

Clinical Efficacy and Learning Curve of Far-Lateral Approach (FLA) in Uni-Portal Non-Coaxial Spinal Endoscopic Surgery (UNSES) in the Treatment of Lumbar Degenerative Diseases: A Prospective Study.

BACKGROUND: Uniportal non-coaxial spinal endoscopic surgery (UNSES) via far-lateral approach (FLA) is an innovative minimally invasive procedure for lumbar degenerative diseases, particularly far-lateral disc herniation and foraminal stenosis. However, complex lateral lumbar anatomy and strict endoscope-instrument coordination create a distinct learning curve that may compromise early surgical efficiency and safety. This study aimed to evaluate the efficacy and safety, quantify the learning curve, and to provide clinical guidance for the standardized promotion and application of this technology. METHODS: A total of 40 consecutive patients with lumbar degenerative diseases who underwent UNSES via FLA by a single surgeon between January 2025 and December 2025 were included. All data were analyzed using SPSS 26.0 statistical software (IBM, USA). Primary outcomes included operation time, blood loss, fluoroscopy frequency, and intraoperative complication rate. Secondary outcomes were VAS, ODI, and modified Macnab criteria at 1, 3, and 6 months postoperatively. The learning curve and the inflection point of the learning curve was determined using cumulative sum (CUSUM) analysis. The differences in clinical indicators between early and proficient stage were compared. RESULT: Operation time, blood loss, and fluoroscopy times decreased significantly with case accumulation (p < 0.05). CUSUM identified an inflection point at the 16th case, after which operation time stabilized at (55.3 ± 8.6) min, much shorter than the early phase (89.5 ± 10.3) min (p < 0.001). Before the 16th case, the curve was in an upward trend; after the 16th case, the curve tended to be flat, indicating the proficiency stage. Postoperative VAS and ODI improved significantly than those before surgery at each follow-up time (p < 0.05). There was no significant difference in postoperative VAS score and ODI between the two groups at each follow-up time point (p > 0.05). The total complication rate was 12.5% (5/40), were cured by conservative treatment. The total excellent-good rate was 90.0% (36/40). L5/S1 and Bertolotti's syndrome were independent factors affecting the learning curve. CONCLUSION: UNSES via FLA is a safe and effective minimally invasive technique for treating complex lumbar degenerative diseases. It has a certain learning curve, and the inflection point is about the 16th case. After mastering the key techniques such as anatomical positioning, endoscopic manipulation and hemostasis, the surgeon can gradually reach the proficiency stage, with significantly improved surgical efficiency and clinical efficacy, and controllable complications. This study provides a theoretical basis for the clinical training and technology promotion of UNSES via FLA.

Humans↗

PubMed2026

Effect of a digitally augmented general health promotion intervention on abstinence from health-risk behaviors among emergency department discharge patients: A randomized controlled trial.

BACKGROUND: Noncommunicable diseases (NCDs) are the leading global cause of death and are driven by modifiable behaviors, such as tobacco use, harmful alcohol consumption, unhealthy diet, and physical inactivity. Recognizing that emergency department (ED) visits represent a unique opportunity to promote behavior change, this trial evaluated a digitally augmented, theory based general health promotion approach, combining a brief telephone-based intervention with mobile instant messaging support, to help discharged ED patients abstain from health risk behaviors. METHODS AND FINDINGS: This assessor-blinded randomized controlled trial was conducted in a major public hospital ED in Hong Kong. Adults (18-65 years) triaged as semi-urgent or non-urgent and with ≥1 health-risk behavior and smartphone access were randomized to receive a digitally augmented, theory‑based general health‑promotion intervention consisting of a brief telephone‑based AWARD‑model intervention (Ask, Warn, Advise, Refer, and Do-it-again) followed by weekly WhatsApp or WeChat messages for 6 months, or to a control group receiving brief telephone advice only. The primary outcome was self-report abstinence from ≥1 health-risk behavior at 6 months; secondary outcomes included the proportion of participants who achieved self-reported abstinence from ≥1 health-risk behavior at 12 months and reduction in the number of behaviors at 6 and 12 months. Of the 2,134 screened patients, 572 were enrolled (286 per group). At 6 months, 30.1% of the intervention participants versus 19.9% of the controls achieved self-reported abstinence (RR = 1.51; 95% CI, 1.13-2.02; P = 0.006). The intervention also significantly increased the likelihood of fewer risky behaviors at 6 (RR = 1.54; P = 0.01) and 12 (RR = 1.48; P = 0.02) months. Physical inactivity showed the greatest improvement at 6 months (31.7% versus 16.2%; P < 0.001). The effects attenuated after cessation of booster messaging. Limitations include reliance on self-reported outcomes, the single-center study design, and loss to follow-up, which may have affected the generalizability of the results. CONCLUSIONS: A digitally augmented, theory-based general health promotion strategy delivered at ED discharge through brief telephone intervention and mobile instant messaging support demonstrated short-term benefits in promoting self-reported abstinence and reducing health-risk behaviors at 6 months. However, the absence of a sustained effect at 12 months suggests that extended support or maintenance strategies may be required to maintain these improvements over time. Multicenter trials with longer follow-up are warranted to evaluate long-term effectiveness. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Registration No: NCT06077565).

Humans↗

PubMed2026

Lower urinary tract evaluation in children with cerebral palsy: A crossectional study.

INTRODUCTION: Cerebral palsy (CP) is a chronic, non-progressive motor disorder affecting voluntary movement and posture. Lower urinary tract (LUT) dysfunction is highly prevalent in children with CP. This study aims to evaluate LUT function in children with CP. MATERIAL AND METHODS: This cross-sectional study was conducted at a tertiary care hospital. Patients aged 5-18 years with established CP diagnosis were included. Evaluation included clinical history, physical examination, urinary ultrasonography with post-void residual (PVR) measurement, and urodynamic studies when indicated. Patients were categorized into three groups; group-1 (LUT dysfunction), group-2 (symptomatic), and group-3 (asymptomatic) for analysis. RESULTS: The study included 97 children with CP (41 girls, 56 boys; median age 8 years). Of the patients, 61.8% were ambulatory (GMFCS I-III) and 38.2% were non-ambulatory (GMFCS IV-V). At least one LUT symptom was detected in 75.3% of patients. Incontinence was the most common symptom at 69.1%. Incontinence prevalence was significantly higher in non-ambulatory patients (81.1% vs 61.7%, p = 0.044). Invasive urodynamics was performed in 19 patients, and LUT dysfunction was diagnosed in 89.5% of them (19.3% of the entire population). Prematurity rate was significantly higher in patients with LUT dysfunction (94.1% vs 64.8%, p = 0.017). Binary logistic regression analysis identified elevated PVR as the strongest independent risk factor for LUT dysfunction (OR = 108, p < 0.001). Abnormal urinary frequency (OR = 14.9, p = 0.022) and quadriplegia (OR = 10.3, p = 0.016) were other independent risk factors. ROC analysis determined the optimal cut-off value for PVR as 19 mL (sensitivity 58.82%, specificity 94.92%). In the intergroup analysis, multinomial logistic regression identified elevated PVR as the strongest predictor (Group-1 vs Group-2: OR = 101; Group-1 vs Group-3: OR = 24, both p < 0.003). Lower gestational age was also an independent risk factor in both comparisons (OR = 1.25-1.26, p < 0.020). DISCUSSION: This study demonstrates LUT dysfunction affects 19.3% of children with CP, strongly correlating with motor impairment severity. Elevated PVR emerged as the strongest independent predictor (OR = 108), offering a practical non-invasive screening tool. Our proposed urodynamic criteria achieved 94.7% diagnostic yield, enabling selective evaluation. Limitations include single-center design and cross-sectional methodology without longitudinal follow-up. These findings support integrating systematic urological assessment into standard CP care for early intervention. CONCLUSION: LUT dysfunction prevalence is high in children with CP, and symptom frequency increases with higher GMFCS levels. Elevated PVR is the strongest predictor, with a clinically applicable cut-off value of 19 mL. Particularly in quadriplegic, non-ambulatory, and premature patients, close follow-up and urodynamic evaluation when necessary should be performed with a multidisciplinary approach.

Humans↗

PubMed2026

Smartphone Apps for Preventing Adolescent Health Problems Among Health Care Professionals: Systematic Search and Quality Assessment.

BACKGROUND: Health care professionals must consider multiple dimensions of prevention when consulting with adolescents. Identifying risky behaviors early in adolescence is crucial for reducing both morbidity and mortality. General practitioners are increasingly eager to incorporate digital tools for prevention into their consultations with adolescents; however, the relevance and clinical validity of these digital tools are not always established or well-known. Consequently, primary care professionals require guidance and support in selecting relevant mobile health (mHealth) tools. OBJECTIVE: The aim of this study is to identify relevant and useful digital apps to help primary care professionals detect at-risk adolescents across all recommended areas of prevention: orthopedics, mental health, substance abuse, risk behaviors, sexual health, vaccinations, social relationships, and nutrition. METHODS: A systematic review of smartphone apps, with an analysis of content quality, was carried out by 4 researchers using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. The App Store and Google Play Store platforms were surveyed. The inclusion criteria were as follows: free of charge, date of last update, availability in French or English, relevance of the preventive approach to adolescents, and scientific validation. Four health care professionals assessed the apps: 2 selected the apps relevant to health care professionals, then 3 analyzed these apps using the French version of the Mobile App Rating Scale (MARS-F). Intraclass correlation coefficient, model (2,1) (2-way random effects, absolute agreement, single measures); standard error of measurement; and mean absolute error were also calculated. RESULTS: A total of 976 apps were identified, 49 of which had disappeared from the platforms prior to analysis. Nine apps were retained. Seven (0.72%) were included after evaluation using the MARS-F: 2 on mental health and 5 on sexual health (including 3 on contraception only). The mean MARS-F interrater score ranged from 2.5/5 to 3.8/5. The global MARS-F score demonstrated a pooled SD of 0.60 and an intraclass correlation coefficient (2,1) of 0.0003, resulting in a calculated standard error of measurement of 0.60. The average discrepancy between raters was a mean absolute error of 0.53. CONCLUSIONS: No similar studies have been identified in the literature that specifically focus on mobile apps designed to support health care professionals in delivering preventive care to adolescents. Of the 8 areas of prevention identified as relevant for adolescents, only 3 are addressed by the apps validated through our methodology (5 focus on sexual health). Consequently, current apps are insufficient to support health care professionals in their overall preventive work with adolescents. Such a review should be conducted systematically prior to the development of any new tool to prevent duplication and channel creative efforts toward truly innovative digital solutions. Furthermore, a thorough analysis of relevant, recommended websites is essential, as these resources complement the use of mobile apps designed for health care professionals.

Humans↗

PubMed2026

Remotely Supervised, Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder: Systematic Review and Meta-Analysis.

BACKGROUND: Major depressive disorder affects over 280 million people worldwide, and access to effective treatment remains limited. Transcranial direct current stimulation (tDCS) is a noninvasive option, and portable devices now allow for home-based delivery under varying degrees of remote supervision. OBJECTIVE: This study aimed to systematically review and meta-analyze the efficacy, safety, feasibility, and acceptability of home-based and remotely supervised tDCS for depressive disorders. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension) guidelines, we searched MEDLINE, Embase, Web of Science, the Cochrane databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to July 2025, with backward and forward citation searching. Two reviewers independently screened records, extracted data, and assessed risk of bias (version 2 of the Cochrane risk-of-bias tool for randomized trials, Newcastle-Ottawa Scale for observational studies, and Critical Appraisal Skills Programme for qualitative studies) and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation; GRADE). RESULTS: This review included 12 distinct studies (16 reports), of which 6 (50%) were randomized sham-controlled trials forming the meta-analytic pool. Active home-based tDCS produced a small, statistically significant improvement over sham (pooled Hedges g=0.36, 95% CI 0.06-0.66; P=.03; I2=34.3%). The effect was not robust to removal of the single largest positive trial (omitting the one study from 2025: g=0.39, 95% CI -0.12 to 0.91), and trial-level results were mixed: the 2 largest trials (one unsupervised [n=210] and one self-administered [n=141]) were negative on their primary depression outcomes, whereas the largest real-time supervised trial (n=174) was positive (between-group 95% CI 0.51-4.01; P=.01). This estimate was concordant in direction with an independent peer-reviewed meta-analysis of overlapping trials, which reported a pooled Montgomery-Åsberg Depression Rating Scale reduction (weighted mean difference -2.74, 95% CI -4.19 to -1.29) and Hamilton Depression Rating Scale reduction (weighted mean difference -2.24, 95% CI -4.16 to -1.49), attenuating to nonsignificance (P>.05) in major depressive disorder without comorbid cognitive impairment. The pooled effect fell at or near the minimal clinically important difference. GRADE certainty was moderate. Adverse events were predominantly mild: one pilot study was terminated early for skin lesions, and one nonfatal suicide attempt occurred in an unsupervised trial. CONCLUSIONS: Home-based and remotely supervised tDCS produces a small, statistically significant but clinically modest antidepressant effect that is sensitive to the inclusion of the largest positive trial, with the 2 largest trials being negative. The available controlled evidence does not establish supervision intensity as a determinant of efficacy. Current data are insufficient to recommend routine clinical adoption; adequately powered trials with standardized supervision and longer follow-up are needed.

Humans↗