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PubMed2026

Effectiveness of a blended care intervention in physiotherapy with exercise and education for patients with hip or knee osteoarthritis (SmArt-E): A multicentre pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a twelve-month smartphone-assisted physiotherapy (SmArt-E) intervention versus usual care in hip and/or knee osteoarthritis (OA), and to assess usability and patient satisfaction with the digital support. METHOD: We conducted a multicentre, pragmatic, parallel-group randomized controlled trial in 27 physiotherapy practices in Germany. Patients with physician-diagnosed hip and/or knee OA aged ≥50 (hip) or ≥38 years (knee) were randomly allocated to SmArt-E (IG; n=166) or usual care (CG; n=164). The twelve-month intervention combined supervised and smartphone-assisted training and education (blended care). Primary outcomes were pain (NRS, 0-10) and physical function (HOOS/KOOS-ADL, 0-100) at twelve months. Secondary outcomes followed OARSI domains; usability and patient satisfaction were also assessed. RESULTS: Among 330 participants (mean age 64±8 years), baseline NRS was 3.2±2.3 in the CG and 3.5±2.4 in the IG; HOOS/KOOS-ADL was 71.6±17.7 and 69.4±17.5, respectively. No significant between-group differences were found for pain (-0.36; 95% CI: -0.84 to 0.12; p=0.14) or physical function (2.66; 95% CI: -0.46 to 5.77; p=0.09). Among 13 secondary outcomes, significant differences favouring the IG emerged at three and twelve months for several domains; however, effect sizes were small and unlikely to be clinically meaningful. CONCLUSION: SmArt-E did not demonstrate superior effectiveness over usual care in mild hip and/or knee OA. Both groups improved over time, with slightly more favourable but clinically inconclusive outcomes in the IG. Findings highlight the need to refine the intervention, better identify eligible patients, and optimize digital and in-person components.

Humans↗

PubMed2026

Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study.

Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE-942 study (ClinicalTrials.gov identifier: NCT03897881). Eligible patients with resected stage IIIB to IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks. The primary end point was recurrence-free survival (RFS); secondary end points included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), the median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5-76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (hazard ratio [HR], 0.510 [95% CI, 0.294 to 0.887) and DMFS (HR, 0.411 [95% CI, 0.200 to 0.843]), with a favorable trend in overall survival (HR, 0.471 [95% CI, 0.165 to 1.345]) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After a 5-year follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.

Humans↗

PubMed2026

Exercise for the mitigation of cancer therapy-related cardiac dysfunction in breast cancer patients treated with anthracyclines: a systematic review and meta-analysis.

PURPOSE: Cancer therapy-related cardiac dysfunction (CTRCD) is a significant concern for breast cancer patients undergoing anthracycline-based chemotherapy. Although exercise has been proposed as a cardioprotective strategy, existing reviews have largely examined heterogeneous cancer populations receiving varied treatments, leaving a gap in the evidence base focused exclusively on anthracycline-induced CTRCD. This systematic review and meta-analysis aimed to address that gap by evaluating the effects of long-term exercise on key CTRCD markers in breast cancer patients treated exclusively with anthracyclines. METHODS: A comprehensive search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science was conducted for randomized controlled trials including breast cancer patients undergoing anthracycline-based chemotherapy, receiving long-term exercise interventions (≥ 12 weeks, ≥ 1 session/week) compared to usual cancer care, and reporting at least one of the following outcomes: left ventricular ejection fraction, global longitudinal strain, cardiac troponin I, cardiac troponin T, or N-terminal prohormone of brain natriuretic peptide. RESULTS: Six randomized controlled trials involving 360 participants were included. Exercise significantly attenuated cardiac troponin I elevation compared to controls (SMD = -0.50; 95% CI, -0.93 to -0.06; p = 0.02). No statistically significant between-group differences were observed for left ventricular ejection fraction, global longitudinal strain, cardiac troponin T, or N-terminal prohormone of brain natriuretic peptide. CONCLUSION: The cardioprotective role of exercise during anthracycline treatment remains uncertain, though the attenuation of cardiac troponin I elevation suggests a potential protective signal warranting further investigation through larger, standardized trials employing advanced assessment modalities and longer follow-up periods.

Humans↗

PubMed2026

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n = 73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5 ± 3.7 before treatment to 8.2 ± 4.1 after treatment (t = 15.900, p < 0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3 ± 2.9 before treatment to 8.0 ± 3.8 after treatment (t = 17.232, p < 0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7 ± 6.8 to 14.0 ± 5.0 (t = 6.363, p < 0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans↗

PubMed2026

Comparison of the Effects of Spinal Versus General Anesthesia on the Perioperative Intraocular Pressure: A prospective, randomized clinical trial.

OBJECTIVES: To evaluate the effects of spinal and general anesthesia on the intraocular pressure (IOP) in patients, who had lumbar spine and lower extremity orthopedic surgeries. METHODS: Sixty adult were randomly classified into Group spinal anesthesia (SA) and Group general anesthesia (GA). The IOP, mean systemic arterial pressure, and heart rhythm were measured at 6 pre-determined timepoints (T0: Baseline, T1: Before spinal procedure or anesthesia induction, T2: After injection with intrathecal or anesthesia induction, T3: 5th minutes (min) after spinal procedure or tracheal intubation, T4: 30th min intraoperative, T5: At the end of surgery, T6: 5th min after surgery or tracheal extubation in the operation room. RESULTS: The baseline IOP and IOP1 measurements during were not significantly different between the groups (SA = 14.28 ± 0.8 mmHg; GA = 14.62 ± 0.9 mmHg, p = 0.923; and IOP1: SA = 15.83 ± 0.9 mmHg; GA = 15.88 ± 0.9 mmHg, p = 0.929). The most significant decrease in IOP in both groups was recorded at T2 (SA: 12.37 ± 0.6. GA: 12.24 ± 0.4, p < 0.001). The decrease in IOP2 was more significant in the GA group. The IOP3 was significantly higher in GA group after intubation (GA: 19.82 ± 1.2, SA: 12.86 ± 1.0)(p < 0.05). The IOP4 and IOP5 in the SA group were lower than those in the GA group. The IOP6 in both groups was higher (SA: 15.20 ± 0.8, GA: 16.50 ± 1.0) than the baseline IOP values, albeit not significant (p > 0.05). In prone position, IOP at the T4 and T5 timepoints were significantly higher than the initial values in both the SA and the GA groups; however, the increase in the GA group was more higher than that of the SA group. CONCLUSION: In intraoperative period, intraocular pressure may increase in both management of anesthesia, but this increase is higher in the general anesthesia group.

Humans↗

PubMed2026

Efficacy of Mindfulness-Based Interventions on Anxiety and Sleep Quality in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Patients with breast cancer commonly experience anxiety and sleep disturbance during and after treatment, and these symptoms are closely interrelated, negatively affecting the quality of life. Mindfulness-based interventions (MBIs) have been increasingly used as a nonpharmacological supportive approach. This systematic review and meta-analysis aimed to evaluate the effects of MBIs on anxiety and sleep quality in patients with breast cancer. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, CINAHL, and Embase was conducted up to May 15, 2025. Random-effects meta-analysis was used to estimate standardized mean differences (SMDs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2.0, and the certainty of evidence was evaluated with Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: Twenty-four randomized controlled trials (RCTs) including 3,212 participants were analyzed. MBIs significantly reduced anxiety compared with control groups receiving usual care, no intervention, or wait-list conditions (SMD: -0.47, 95% CI: -0.62 to -0.32), whereas no significant effect was observed for sleep quality. Subgroup analysis indicated that intervention duration accounted for 55.5% of the heterogeneity in anxiety outcomes. All studies were rated as having some concerns regarding risk of bias, primarily due to self-reported outcomes and lack of blinding. Certainty of evidence was moderate for anxiety and low for sleep quality. DISCUSSION: MBIs appear to be effective in reducing anxiety among patients with breast cancer; however, no significant effect was observed for sleep quality. All included studies were rated as having some concerns regarding risk of bias, and the limited reporting of adverse events represents a limitation of the evidence. In addition, substantial heterogeneity in sleep quality outcomes and the limited number of included RCTs restrict exploration of heterogeneity sources and limit generalizability. Further high-quality well-designed RCTs are needed to strengthen and confirm the evidence.

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PubMed2026

Characterizing Caregiver-Child Interactions Through a Transactional Lens: A Baseline Analysis of a Caregiver-Implemented Intervention.

PURPOSE: This study was motivated by the transactional model of development and examined the reciprocal influences that children and caregivers have on caregiver-child interactions (CCXs) prior to a caregiver-implemented intervention. We tested whether child communication characteristics were associated with caregiver strategy use and whether these strategies, in turn, influenced children's communication to understand how caregivers and children mutually shaped the language learning environment. METHOD: Caregiver-child dyads (N = 105) were participants in a randomized controlled trial. CCXs were collected when children were approximately 30 months of age, transcribed, and coded for four caregiver language facilitation strategies and child communication variables. RESULTS: Least Absolute Shrinkage and Selection Operator regression and postselection inference indicated that child communication characteristics in CCXs were associated with both the frequency and type of strategies caregivers used. Children's overall communication acts were significantly associated with caregiver use of vocabulary strategies, whereas children's vocabulary diversity was significantly associated with caregiver use of sentence strategies. Mixed-effects logistic regression demonstrated that all four caregiver strategies significantly increased the likelihood of spontaneous lexical overlap in subsequent child turns. CONCLUSIONS: Prior to the intervention, caregivers and children reciprocally shaped the language environment. This supports a transactional perspective and warrants further consideration of reciprocal influences when assessing the impact of caregiver-implemented interventions. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.32995796.

Humans↗

PubMed2026

Impact of oliceridine versus sufentanil on postoperative nausea and vomiting in patients undergoing thyroid surgery: a prospective, double-blind, randomized controlled trial.

PURPOSE: Postoperative nausea and vomiting (PONV) is a common complication following thyroid surgery, often exacerbated by opioid use. Oliceridine, a novel G protein-biased μ-opioid receptor agonist, may reduce opioid-related adverse events. This study aimed to compare the impact of oliceridine versus sufentanil on the incidence and severity of PONV in patients undergoing thyroid surgery. PATIENTS AND METHODS: In this prospective, double-blind, randomised controlled trial conducted between May 2025 and February 2026, 232 patients scheduled for thyroid surgery were randomly assigned to receive either oliceridine or sufentanil for intraoperative analgesia. The primary outcome was the incidence of PONV during the first 48 h postoperatively. Secondary outcomes included PONV severity, need for rescue anti-emetics, postoperative pain scores, recovery quality, and other adverse events. RESULTS: The incidence of PONV within 48 h postoperatively was significantly lower in the oliceridine group [13/107 (12%)] compared with the sufentanil group [31/110 (28%)] (OR = 0.35, 95% CI: 0.17-0.72, p = 0.006). Postoperative pain scores, rescue analgesia requirements, and Quality of Recovery-15 scores were comparable between the two groups (p > 0.05). Besides, exploratory unadjusted analyses revealed fewer rescue anti-emetics: O group 8/107 (8%) vs S group 25/110 (23%) (OR = 0.27, 95% CI: 0.12-0.64, p = 0.002); and less abdominal distension: O group 4/107 (4%) vs S group 19/110 (17%) (OR = 0.19, 95% CI: 0.06-0.57, p = 0.001). CONCLUSION: For young ASA I-II patients undergoing thyroid surgery, oliceridine yields adequate postoperative analgesia and lower PONV rates versus sufentanil. Additional trials involving high-intensity surgical procedures are needed to confirm consistent equivalence.

Humans↗

PubMed2026

Teaching Acute Coronary Syndrome High-Risk ECG Interpretation and Clinical Decision-Making Through FOAMed Videos and Podcast Versus Print-Based Materials Among Emergency Care Providers: Randomized Controlled Mixed Methods Trial.

BACKGROUND: Accurate interpretation of high-risk acute coronary syndrome (ACS) electrocardiograms (ECGs) is essential for early diagnosis and timely reperfusion, yet substantial deficits persist across health care professions. Digital self-learning formats such as FOAMed (Free Open Access Medical Education) are widely used, but their effectiveness has rarely been evaluated for complex, high-risk ACS ECG patterns. Existing ECG education studies often focus on students or single professional groups and established ST-segment elevation myocardial infarction (STEMI) criteria, leaving newer guideline-recognized STEMI equivalents, selected emerging occlusion myocardial infarction (OMI)-related patterns, and interprofessional emergency care underrepresented. OBJECTIVE: This study aimed to compare the effectiveness of FOAMed podcast and videos versus traditional print-based materials for teaching high-risk ACS ECG patterns and related clinical decision-making in emergency providers. METHODS: We conducted a prospective, interprofessional, controlled mixed methods trial across 5 training sites in Germany. Paramedics, prehospital emergency physicians, and emergency department clinicians received either a FOAMed multimedia module or print-based materials through concealed allocation; deviations from the intended 1:1 ratio resulted from participant no-shows. The intervention consisted of a 30-minute supervised self-learning session. In total, 103 participants were allocated to FOAMed (n=45) or print-based materials (n=58). Two coprimary outcomes were assessed: ECG interpretation accuracy and text-based ACS clinical decision-making. Secondary outcomes included subjective confidence, learning experience, and exploratory qualitative free-text responses. Outcome assessment was automated and blinded; mixed ANOVA was the primary analysis. The study was not prospectively registered because it assessed educational outcomes in health care professionals rather than patient health outcomes. RESULTS: All 103 participants completed the study. Both groups improved, with greater gains in the FOAMed group: ECG interpretation increased from 55% to 65.5% and text-based ACS clinical decision-making from 45% to 68%, versus 57% to 60% and from 47% to 63%, respectively, in the print-based group. Effect sizes were η²=0.055 for ECG interpretation and η²=0.044 for clinical decision-making. Exploratory subgroup analyses provided no evidence of differential effects across age, gender, or professional background and were likely underpowered. Qualitative responses (46 and 37 entries) provided contextual insights into perceived clarity, engagement, and practical relevance supporting the quantitative findings. CONCLUSIONS: This study is innovative in directly comparing a curated FOAMed multimedia module with selected print-based materials in an interprofessional emergency care population. It differs from existing research by focusing on subtle, emerging ischemic patterns and evaluating realistic, time-limited self-learning formats. The findings provide evidence that curated FOAMed resources can produce greater short-term improvements in ECG interpretation and text-based ACS clinical decision-making than traditional print-based materials in this setting. Although implications for clinical performance remain hypothetical, concise, high-quality digital modules may represent a practical supplement to structured continuing education in emergency care.

Humans↗

PubMed2026

A pragmatic randomized controlled trial of self-directed online writing interventions for posttraumatic stress symptoms in a real-world digital setting.

Background: Public health and other large-scale crises, such as the COVID-19 pandemic, have intensified the global mental health burden, creating unprecedented demand for accessible interventions for posttraumatic stress symptoms (PTSS).Objective: We evaluated the feasibility and effectiveness of two self-directed online writing interventions embedded within China's WeChat ecosystem during the COVID-19 pandemic through a pragmatic randomised controlled trial.Methods: Between December 2021 and August 2022, 1,526 adults were screened for PTSS via a Tencent Medinfo Mini-Program. Eligible participants (n = 211) were randomised to Guided Narrative Technique-Writing (GNT-W, n = 100) or Expressive Writing (EW, n = 111). Both interventions comprised three self-directed daily writing sessions delivered entirely online without human support. Primary outcome was PTSD symptom severity (PTSD Checklist-Short), assessed at baseline, post-intervention, 2-week, and 1-month follow-ups.Results: While initial engagement followed typical digital health patterns (64.5% overall attrition), participants who initiated treatment showed strong adherence (77% completion). Both interventions were associated with significant within-group reductions in PTSS severity (GNT-W: b = -0.43, p = .023, d = -0.43; EW: b = -0.60, p = .001, d = -0.58), with no significant between-group difference (group × time: b = 0.18, p = .48). GNT-W did not confer additional benefit over EW protocol on PTSS severity.Conclusions: Both self-directed writing interventions were associated with within-group reductions in PTSS; without an inactive control condition, however, these changes cannot be firmly attributed to the interventions. GNT-W showed no advantage over the simpler EW protocol. These findings offer preliminary support for embedding scalable, low-barrier writing interventions in widely used digital platforms.Chinese Clinical Trial Registry: ChiCTR2000034836.

Humans↗

PubMed2026

Phase IIB, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intravenous Defibrotide for the Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome in COVID-19.

INTRODUCTION: Endothelial dysfunction is key in COVID-19 pathogenesis. This randomized, double-blind phase IIb trial investigated continuous intravenous infusion of defibrotide in patients hospitalized with SARS-CoV-2 infection and respiratory failure. METHODS: One-hundred and fifty patients were randomized (2:1) to defibrotide or placebo, stratified by disease severity (WHO COVID-19 severity scale 4/5 vs. 6). The primary endpoint was clinical improvement time (days from first improvement through Day 30). RESULTS: Median clinical improvement time was not significantly different with defibrotide versus placebo (15.0 [IQR: 0-24] vs. 20.0 [IQR: 9-25] days; p = 0.10). Day-30 (23.0% vs. 22.0%) and Day-60 (26.0% vs. 22.0%) mortality, reduction in mean fraction of inspired oxygen during treatment, and median duration of hospitalization did not differ with defibrotide versus placebo. Defibrotide demonstrated favorable safety, with no differences versus placebo in serious adverse events (34.0% vs. 36.0%), hypotension (16.0% vs. 12.0%), or hemorrhage (13.0% vs. 8.0%). Exploratory pre-specified biomarker analyses showed greater early d-dimer reduction and lymphocyte recovery with defibrotide, although these results require validation. CONCLUSION: Continuous intravenous infusion of defibrotide was safe but did not improve clinical outcomes in severe COVID-19. Further analyses will explore mechanistic actions and pharmacokinetics of defibrotide and the pathophysiology of endothelial dysfunction in COVID-19. TRIAL REGISTRATION: EudraCT identifier: 2020-001409-21. CLINICALTRIALS: gov identifier: NCT04348383.

Adult↗

PubMed2026

Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4+ T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans↗

PubMed2026

Effect of walking training on blood glucose control and metabolic health in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the improvement effect of walking training on blood glucose control and metabolic health indicators in type 2 diabetes patients, and to explore the effect of different intervention program characteristics on the efficacy through subgroup analysis. METHOD: The system searched PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO databases, with a search period from the establishment of the database to March 15, 2026. Include a randomized controlled trial with the main intervention measures of walking behavior, with an intervention period of ≥8 weeks. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. Meta-analysis was conducted using RevMan 5.4 software, with mean difference (MD) and its 95% confidence interval (CI) as effect measures for continuous variables. Select fixed effects model or random effects model for combined analysis based on heterogeneity size, and conduct subgroup analysis according to intervention program characteristics. RESULTS: Totally 5 randomized controlled trials were included, including 483 patients with type 2 diabetes (241 cases in the intervention group and 242 cases in the control group). Participants had a mean age of 54.2 ± 6.5 years, BMI of 29.1 ± 3.2 kg/m2, and 48.5% were male. The meta-analysis results showed that walking training significantly reduced glycated hemoglobin levels, with a combined effect of -0.48% (95% CI: -0.60 to -0.36, P < 0.00001), There is moderate heterogeneity among the studies (I2 = 67%). Subgroup analysis showed that the "walking + other interventions" subgroup (combined effect size -0.58%, 95% CI: -0.96 to -0.20) and the "clear step target" subgroup (combined effect size -0.52%, 95% CI: -0.65 to -0.39) had larger effect sizes and lower heterogeneity within the subgroups. The bias risk assessment shows that the overall quality of the included research methodology is good. CONCLUSION: Walking training can significantly improve the blood glucose control in patients with type 2 diabetes. Combined with diet or behavioral intervention, setting clear goals for the number of steps may achieve better results. Walking training can be used as an effective auxiliary treatment for the management of type 2 diabetes in clinical promotion. Due to limitations in the number and quality of studies included, the above conclusions still require more high-quality research to validate.

Humans↗

PubMed2026

Cognitive Behavioral Therapy vs Media Literacy for Prevention of Gaming Disorder and Unspecified Internet Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Mitigating the harmful effects of digitalization on youth mental health is essential. OBJECTIVES: To evaluate the effectiveness of cognitive behavioral therapy (CBT) compared with a media literacy-based intervention for gaming disorder and unspecified internet use disorder and to determine whether universal or indicated prevention yields stronger benefits. DESIGN, SETTING, AND PARTICIPANTS: PROTECTconfirm was a randomized clinical trial conducted from July 1, 2020, to August 31, 2024, across 44 secondary schools in Baden-Württemberg, Germany, with 1-, 4-, and 12-month follow-up. All students were included in universal prevention analyses, whereas indicated prevention analyses included a subgroup of adolescents at high risk meeting 2 or more Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for gaming disorder or unspecified internet use disorder at baseline. INTERVENTIONS: Students were individually randomized within 90 classes to PROTECTtraining, a CBT-based program; or PROTECTinfo, a structurally parallel media literacy program. Both consisted of four 90-minute sessions delivered weekly during school hours by trained local prevention professionals under live supervision and adherence protocols. MAIN OUTCOMES AND MEASURES: The primary outcome was gaming disorder symptom severity and unspecified internet use disorder symptom severity, assessed at 12 months with a modified version of the Video Game Dependency Scale. Secondary outcomes included internalizing, externalizing, and transdiagnostic symptoms. Primary and secondary outcomes were analyzed according to the intention-to-treat principle. RESULTS: A total of 1793 students were randomized to PROTECTtraining (n = 896; mean [SD] age, 13.1 [1.5] years; 498 male students [56.1%]) or PROTECTinfo (n = 897; mean [SD] age, 13.1 [1.5] years; 484 male students [54.8%]). Participants in the subsample of 205 adolescents at high risk showed significantly lower 12-month severity of gaming disorder and unspecified internet use disorder symptoms with PROTECTtraining than with PROTECTinfo (mean [SD] Modified Video Game Dependency Scale score: 14.7 [9.7] vs 17.7 [10.3]; within-group Cohen d = -0.91 [95% CI, -1.10 to -0.72] vs Cohen d = -0.61 [95% CI, -0.80 to -0.42]; between-group Cohen d = -0.30 [95% CI, -0.55 to -0.05]), but not in the total sample (mean [SD] Modified Video Game Dependency Scale score: PROTECTtraining, 8.8 [8.3] vs PROTECTinfo, 9.4 [8.4]; within-group Cohen d = -0.11 [95% CI, -0.18 to -0.05] vs Cohen d = -0.04 [95% CI, -0.11 to 0.02]; between-group Cohen d = -0.07 [95% CI, -0.16 to 0.01]). Secondary outcomes did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of 1793 adolescents, the CBT-based intervention reduced gaming disorder symptoms and unspecified internet use disorder symptoms more effectively than the media literacy-based intervention among adolescents at high risk. These findings support the use of CBT-based approaches primarily within indicated, rather than universal, prevention. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) trial registration: DRKS00033989.

Humans↗

PubMed2026

Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

BACKGROUND: A bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. METHODS: We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). RESULTS: Nine studies were included (3 RCTs, 6 retrospective cohort studies; n = 148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1·08, 95% CI 1·02-1·13; p = 0·004; I2 = 44%), driven by the observational studies group (1·08, 1·02-1·14; I2 = 61%); RCTs showed a directionally consistent but non-significant RR (1·12, 0·87-1·43; I2 = 0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. CONCLUSION: Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.

Humans↗

PubMed2026

Effects of Photobiomodulation Therapy in Lateral Luxation of Anterior Permanent Teeth: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Among the traumatic dental injuries (TDIs), lateral luxation may present poor prognosis due to frequent root resorption and consequent tooth loss. Photobiomodulation therapy (PBMT) modulates cellular activities (proliferation, differentiation, growth factor secretion) and may improve outcomes. OBJECTIVE: This randomized, double-blind, placebo-controlled trial evaluated PBMT (660 vs. 808 nm) for post-operative pain and pulp sensitivity recovery in lateral luxation of permanent anterior teeth. METHODS: Initially, 41 patients were included, with a total of 63 teeth traumatized by lateral luxation and were allocated to G1 (n = 21): Splinting + sham PBM (placebo), G2 (n = 21): Splinting + 808 nm infrared PBM and G3 (n = 21): Splinting + 660 nm red PBM. Four weekly sessions (3 J/point, 3 points) were administered. Pain (by numeric rating scale) and pulp sensitivity (by cold test) were assessed weekly. Pain was analyzed using the Kruskal-Wallis test, followed by multiple comparisons using Dunn's method with Bonferroni correction, and pulp sensitivity by a logistic regression model (p < 0.05). RESULTS: Three participants (total of 5 teeth) were excluded due to loss to follow-up. Fifty-eight teeth were analyzed (G1 = 21, G2 = 17, G3 = 20). Pain: All groups showed a significant reduction in pain over time (p < 0.001). Both G2 and G3 demonstrated a significantly greater reduction in pain compared to G1 (p < 0.001 and p = 0.026, respectively). No significant difference in pain reduction was observed between G2 and G3. Pulp sensitivity: G2 showed a significant improvement over time (p < 0.001), despite starting from a more unfavorable baseline. In contrast, no significant change in pulp sensitivity was observed for G1 or G3 between the initial and final assessments. CONCLUSION: Within the limitations of this clinical study, all intervention groups were effective in reducing pain in lateral luxation of permanent anterior teeth, with superior results for laser groups compared to the placebo. However, only the 808 nm laser irradiation protocol demonstrated a significant improvement in pulp sensitivity, suggesting it may offer a more complete therapeutic response.

Humans↗

PubMed2026

Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703).

IMPORTANCE: In a phase 2 randomized clinical trial, high-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared with standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC). OBJECTIVE: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC. DESIGN, SETTING, AND PARTICIPANTS: Double-blind phase 3 randomized clinical trial enrolling 455 patients with previously untreated mCRC, conducted in the US through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024). INTERVENTIONS: mFOLFOX6 (modified FOLFOX6 [5-fluorouracil, leucovorin, oxaliplatin]) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab every 2 weeks with either high-dose vitamin D3 (8000 IU daily × 14 days as loading dose followed by 4000 IU daily) or standard-dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent. MAIN OUTCOMES AND MEASURES: The primary end point was PFS assessed by the unstratified log-rank test. Secondary end points included objective response rate, overall survival, and toxicity. Prespecified subgroup analyses of PFS were performed according to known prognostic factors. RESULTS: Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow-up 20 months, the median PFS for high-dose vitamin D3 (n = 228) was 11.8 months (95% CI, 10.3-13.3) vs 10.3 months (95% CI, 9.4-12.2) for standard-dose vitamin D3 (n = 227) (1-sided log-rank P = .25). There were no significant differences in objective response rate between high-dose and standard-dose vitamin D3 (51% [95% CI, 44%-58%] vs 44% [95% CI, 37%-50%], respectively; P = .12), or in overall survival (median, 25.6 vs 27.0 months; 1-sided log-rank P = .66). There were no clinically meaningful differences in the most common grade 3 or greater adverse events between the high- and standard-dose groups, including neutropenia (n = 67 [32%] vs n = 62 [30%]) and hypertension (n = 42 [20%] vs n = 49 [23%]) or in incidence of vitamin D-associated toxicities. CONCLUSIONS AND RELEVANCE: Among patients with previously untreated mCRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04094688.

Aged↗

PubMed2026

Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial.

IMPORTANCE: Combination therapy has emerged as a promising therapeutic approach for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, its clinical benefit-risk profile remains a focus of ongoing debate. Identifying patients most likely to derive benefit from such regimens remains an unmet clinical need. OBJECTIVE: To prospectively compare the efficacy and safety of first-line osimertinib plus chemotherapy with osimertinib monotherapy for patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, open-label, phase 3 study conducted at 17 sites in China. Between March 25, 2021, and July 11, 2024, a total of 294 eligible patients with treatment-naive, stage IV or recurrent nonsquamous NSCLC harboring concurrent TP53 and EGFR-sensitizing mutations were enrolled. INTERVENTIONS: Patients were randomized (1:1) to receive osimertinib plus chemotherapy (pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance therapy of osimertinib plus pemetrexed; n = 146) or osimertinib monotherapy (n = 148). MAIN OUTCOMES AND MEASURES: The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, response, safety, and quality of life. RESULTS: Among 294 enrolled patients, the median age was 57 years (range, 26-79 years), and 159 (54.1%) were female. The data cutoff date was November 11, 2025. At a median follow-up of 25.1 months for the osimertinib-chemotherapy group and 26.1 months for the osimertinib monotherapy group, median progression-free survival was significantly longer with osimertinib plus chemotherapy than with osimertinib monotherapy (34.0 vs 15.6 months; difference, 18.4 months [95% CI, 9.9-22.3]; hazard ratio, 0.44 [95% CI, 0.32-0.60]; P < .001). This benefit was consistent across prespecified subgroups, including those with brain metastases and L858R mutations. The overall survival data remained immature (30.6% maturity); however, a trend toward overall survival benefit with combination therapy was observed. The incidence of grade 3 or higher treatment-related adverse events was higher in the combination group, with no new safety signal identified. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, osimertinib plus chemotherapy significantly increased progression-free survival among patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. These findings provided a clinical rationale for individualized combination strategies in the management of patients with EGFR-mutated NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04695925.

Adult↗