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PubMed2026

Intraocular Pressure Changes Following Intraluminal Stent Removal From the Paul Glaucoma Implant: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to systematically review and perform a single-arm meta-analysis to comprehensively evaluate the effect of removal of intraluminal stent from the Paul glaucoma implant (PGI) on intraocular pressure (IOP) changes and to summarize its long-term efficacy and safety. CLINICAL RELEVANCE: Glaucoma remains one of the leading global causes of irreversible vision loss, necessitating effective surgical management for refractory cases. Glaucoma drainage devices are critical for these complex forms, and intraluminal stent removal from the PGI serves as a key strategy to titrate aqueous outflow and optimize long-term IOP control. METHODS: A systematic review was conducted by searching EMBASE, Medline, and CENTRAL. The meta-analysis ultimately included 5 observational studies. The Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool was used to assess the quality of the included studies. Continuous outcomes (eg, postremoval stent IOP reduction) were analyzed using the mean difference (MD) with 95% confidence intervals (CI); dichotomous outcomes (eg, hypotony incidence) were evaluated using pooled proportion with 95% CI. All meta-analyses employed a random-effects model. RESULTS: Our meta-analysis included 5 studies, involving a total of 283 eyes. The meta-analysis revealed that removal of the stent leads to a significant and immediate IOP reduction. The IOP reduction (immediate postremoval stent IOP minus preremoval stent IOP) was significant, with a pooled MD of -9.09 mm Hg IOP (MD = 9.09; 95% CI = [-11.77, -6.41]). In the preremoval stent high-IOP (>21 mm Hg) subgroup, the IOP reduction is -11.82 (95% CI = [-10.14, -13.51]). This reduction was significantly greater than the preremoval stent low-IOP (<21 mm Hg) subgroup, whose reduction is -6.66 mm Hg (95% CI = [-5.55, -7.77]). Regarding safety, the pooled proportion of clinically hypotony was low and highly consistent (I² = 0.00%) at only 0.03 (95% CI = [0.00, 0.15]). CONCLUSIONS: Intraluminal stent removal from the PGI is an effective and safe IOP-lowering intervention. Its IOP reduction effect is significantly more pronounced in patients with preremoval stent high IOP, providing crucial clinical guidance for managing persistently high IOP after PGI implantation.

Humans↗

PubMed2026

Psychotherapy vs antidepressants in heart failure: Impact of adherence.

BACKGROUND: Depression affects nearly half of patients with heart failure (HF), which is associated with increased morbidity and reduced health-related quality of life (HRQoL). This secondary per-protocol analysis of a previously published randomized trial evaluated the behavioral activation (BA) versus antidepressant medication (MEDS) among patients with depression and HF who adhered to study interventions. METHODS: This analysis is based on a pragmatic randomized comparative-effectiveness trial conducted from 2018 to 2022, with a 1-year follow-up. 416 participants diagnosed with HF and a DSM-5 depressive disorder were randomized to BA or MEDS, and the current analysis examined outcomes according to treatment adherence. OUTCOMES: The primary outcome was depressive symptom severity (PHQ-9) at 6 months, and the secondary outcomes were physical and mental HRQoL (SF-12v2-PC and SF-12v2-MC, respectively) and HF-specific HRQoL (Kansas City Cardiomyopathy Questionnaire; KCCQ) overall and clinical scores (KCCQ-OS and KCCQ-CS), at 3, 6, and 12 months. High adherence was defined as completion of >75-100% of intervention components. Overall adherence rates were similar between BA and MEDS. At 6 months, among patients with >75-100% adherence who followed treatment as directed in both arms, BA was associated with higher Mental HRQoL (SF-12v2-MC: 5.22; 95% CI: 0.72 to 9.72; p = 0.023) and higher HF-specific HRQoL (KCCQ-OS: 16.08; 95% CI: 7.20 to 24.97; p < 0.001); (KCCQ-CS: 16.04; 95%CI: 7.05 to 25.02; p < 0.001) compared to MEDS. There were no significant differences in depressive symptoms or physical HRQoL at 6 months. INTERPRETATION: Both BA and MEDS were equally effective treatments for depression in HF. However, among highly adherent patients, BA was associated with greater improvements in mental and HF-specific HRQoL than MEDS. FUNDING/SUPPORT: The study was funded by PCORI Award Number: 2017C2-7716.

Humans↗

PubMed2026

Effects of Exergame Balance Training with Variable Cognitive Motor Challenges on Serum BDNF, p-tau181, and Cognitive Functions in Adults with Mild Cognitive Impairment: A Randomized Trial.

INTRODUCTION: Cognitive-motor exergame balance training may increase attentional demands and neuronal processing, potentially affecting serum levels of brain-derived neurotrophic factor (BDNF), Aβ1-42, and p-tau181, as well as train cognitive abilities in adults with mild cognitive impairment (MCI). This study aimed to compare the effects of exergame balance training of mild, moderate, high-difficulty, and Wii Fit™ groups on blood serum levels of BDNF, Aβ1-42, p-tau181, and cognition function in adults with MCI. METHODS: In this four-arm, parallel group randomized clinical trial, 97 adults with MCI were randomly assigned to exergame balance training groups of mild, moderate, high-difficulty, and Wii Fit exergame as a control group. All participants received 40 min/session, 3 times/week for 8 weeks. Assessment of serum levels of p-tau181, Aβ1-42, BDNF, and cognitive functions was conducted at baseline, after weeks 4 and 8. A mixed-model analysis of covariance was used, with post-baseline measurements (weeks 4 and 8) specified as the within-subject factor and the corresponding baseline value entered as a covariate to adjust for initial between-group variability. RESULTS: A significant group × time interaction was found for BDNF, F(3,92) = 6.413, P = 0.017, ηp2 = 0.181; p-tau181, F(3,92) = 4.640, P = 0.040, ηp2 = 0.138; attention, F(3,92) = 4.171, P = 0.045, ηp2 = 0.057; abstraction, F(3,92) = 4.263, P = 0.043, ηp2 = 0.058; and visuospatial skills, F(3,92) = 6.931, P < 0.001, ηp2 = 0.234. CONCLUSION: Cognitive-motor challenge-based exergame balance training was associated with an increase in serum BDNF, a reduction in p-tau181. In contrast, the Aβ1-42 levels remained stable. These changes were accompanied by improvement in selective cognitive functions (attention, abstraction, and visuospatial skills) in individuals with MCI. Greater effects were observed in moderate and high-difficulty groups, suggesting the importance of intervention intensity in promoting cognitive and neurobiological outcomes in MCI.

Humans↗

PubMed2026

Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial.

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2 × 3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time × group interaction was detected for any ES biomarker, including 2-AG (F(2,88) = 0.17, p = 0.844) and AEA (F(2,88) = 1.20, p = 0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference + 81.6 m at 12 weeks (F(2,78) = 7.88, p = 0.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78) = 2.83, p = 0.065). CONCLUSION: A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

Humans↗

PubMed2026

Biomarker Analysis from Patients with Metastatic PDAC Treated with TGFβ Antibody NIS793 plus Abraxane + Gemcitabine versus Abraxane + Gemcitabine Alone in a Phase II, Open-Label, Randomized Study.

PURPOSE: Transforming growth factor β (TGFβ) plays a dual role in cancer, acting as a tumor suppressor early in the disease but promoting progression and immune evasion when dysregulated. In pancreatic ductal adenocarcinoma (PDAC), TGFβ-driven desmoplasia fosters chemoresistance and immunosuppression, limiting therapeutic efficacy. NIS793, a fully human mAb targeting TGFβ, demonstrated antifibrotic and immunomodulatory activity in preclinical models and early-phase trials. PATIENTS AND METHODS: We conducted a randomized, open-label, phase II study in treatment-naïve patients with metastatic PDAC (mPDAC) to evaluate NIS793 ± spartalizumab (anti-PD-1) combined with nab-paclitaxel (or Abraxane)/gemcitabine (ABRA/GEM) versus ABRA/GEM alone. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), safety, pharmacokinetics, and biomarker analyses. Exploratory assessments included paired tumor RNA sequencing, cell-free DNA profiling, and plasma proteomics. RESULTS: NIS793 demonstrated target engagement and suppression of TGFβ signaling, confirmed by transcriptomic and proteomic analyses. Stromal remodeling was evident, with significant downregulation of cancer-associated fibroblast markers (Acta2, Fap) and collagen-related signatures. Despite proof of mechanism, clinical efficacy was not observed: Median PFS and OS were comparable or numerically worse in the NIS793 arm versus control (HR for OS in NIS793 + ABRA/GEM vs. ABRA/GEM: 1.32; 95% confidence interval, 0.84-2.07). The safety profile was manageable, with no unexpected toxicities. Biomarker data revealed increased expression of neutrophil-related genes after treatment, suggesting potential induction of tumor-promoting inflammation. CONCLUSIONS: NIS793 effectively inhibited TGFβ signaling and led to stromal remodeling but failed to improve outcomes in mPDAC. These findings highlight the complexity of TGFβ biology and caution against its blockade in combination with chemotherapy for PDAC. Future strategies should consider context-dependent effects of TGFβ inhibition.

Humans↗

PubMed2026

Sensor-based measures of knee brace adherence have low agreement with self-report methods: A multi-measure study among knee osteoarthritis patients.

OBJECTIVE: To explore agreement between self-report and objectively measured adherence to brace wearing by patients with knee osteoarthritis. METHOD: A single-arm observational analysis nested within the PROP OA randomised controlled trial (ISRCTN28555470). Of 237 adults with symptomatic knee osteoarthritis randomised to brace treatment, 60 were included in this sub-study investigating three different methods of assessing knee brace wear time over 26 weeks: 1. Self-report questionnaires (SRQ) at 12 weeks and 26 weeks; 2. Short message service (SMS) questions (days worn in past week, typical hours per day when worn) administered from week 1 to week 24; 3. A skin temperature sensor embedded in the brace, sampling every 10 min for 26 weeks. The presence and reason for the sensor were concealed from participants. The estimated proportion of participants meeting "minimum brace use", defined a priori as ≥1 h on ≥2 days in past week, was described for each measurement method, overall and by brace type (unloader, neutral). For temperature sensor measurements, time spent above 24°C and time spent above 25°C were used. Agreement between the measures was summarised by percentage agreement and kappa (ĸ). RESULTS: The estimated proportions of participants meeting "minimum brace use" at 12 weeks were 83% (SRQ), 83% (SMS), 60% and 58% (temperature sensor, 24°C and 25°C thresholds, respectively). At 26 weeks, the corresponding estimates reduced to 72%, 71% (SMS at 24 weeks), 43% and 37%. Sensor data suggested the sharpest decline in brace use occurred within the first 12 weeks. Agreement between self-report measures was higher than between self-report measures and sensor (SRQ vs SMS at 12 weeks: 92% agreement, ĸ=0.67 (95%CI: 0.34, 1.00); SRQ vs Sensor at 12 weeks: 74%, 0.35 (0.10, 0.60); SMS vs Sens at 12 weeks: 76%, 0.36 (0.05, 0.66). Agreement between all measurement methods reduced at 26 weeks. CONCLUSIONS: This novel use of a temperature sensor to monitor brace adherence in knee osteoarthritis indicates that self-report adherence substantially overestimates knee brace wearing time, with implications for clinical trials and practice.

Humans↗

PubMed2026

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (∼19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (∼6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Psychedelic microdosing has gained increasing popularity for enhancing mood and cognition, yet its effects on psychological outcomes in healthy adults remain unclear. We aim to evaluate the efficacy and safety of psychedelic microdosing on psychological outcomes in healthy/non-clinical adult population. METHODS: This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251035294). We searched Embase, MEDLINE, and PsycINFO from inception to February 2026 for original studies in healthy adults using sub-hallucinogenic psychedelic doses on separate days. We included randomized studies, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal designs and stratified meta-analyses by design. Random-effects models were used; safety in randomized controlled trials (RCTs) was pooled as risk differences (RDs). Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. RESULTS: 24 studies (3,681 participants) met inclusion criteria, 6 contributed to meta-analyses. RCTs of psilocybin and LSD microdosing showed subjective and neurophysiological effects but minimal impact on cognition, creativity, or sustained mood. Psilocybin altered EEG and speech with little behavioral change, while LSD caused transient mood and minor physiological effects without lasting cognitive or personality benefits. Observational studies indicated mood and personality improvements, likely influenced by expectancy or lifestyle factors. Meta-analyses included two parallel RCTs (3 comparisons; n = 117) and three non-RCT studies (n = 1,013). Adverse event analyses included two RCTs (4 comparisons; n = 109). RCTs showed no clear evidence of immediate symptom reduction: depressive symptoms (SMD = -0.19; 95% CI -0.56, 0.19; I2 = 0%), anxiety (SMD = -0.20; 95% CI -1.11, 0.71; I2 = 82.3%),and stress (SMD = 0.02; 95% CI -0.39, 0.43; I2 = 0%). Non-RCT within-arm estimates were imprecise and heterogeneous for depressive symptoms (SMCC -0.33; 95% CI -0.75, 0.08) and anxiety (SMCC -0.29; 95% CI-0.84, 0.26). Exploratory pooling across all designs suggested decreases in depressive symptoms and stress, while anxiety remained uncertain. Adverse event risks were similar between treatment and control. CONCLUSIONS: Microdosing does not show consistent immediate benefits for depressive, anxiety, or stress symptoms in healthy adults, and evidence from RCTs remains inconclusive. Although improvements were observed in some studies, these effects were not significantly different from placebo. Larger, well-designed RCTs are needed to clarify the efficacy and safety of psychedelic microdosing beyond placebo.

Humans↗

PubMed2026

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n = 65) or routine nursing only (n = 65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6 months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6 months ranged from small for resilience (D = 0.28) and avoidance coping (D = 0.26) to moderate for confrontation coping (D = 0.60) and resignation coping reduction (D = -0.51), and large for attributional style (D = 0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans↗

PubMed2026

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses↗

PubMed2026

High-frequency contralesional dorsal premotor cortex and low-frequency contralesional primary motor cortex rTMS in subacute stroke with severe upper limb impairment: comparable motor outcomes and differential regional degree centrality changes.

BACKGROUND: The contralesional dorsal premotor cortex has been proposed as a potential neuromodulatory target for patients with severe upper limb impairment due to subacute ischemic stroke. This proof-of-concept study aimed to compare behavioral outcomes and resting-state neuroimaging findings between high-frequency repetitive transcranial magnetic stimulation (rTMS) over the contralesional dorsal premotor cortex and guideline-supported low-frequency stimulation over the contralesional primary motor cortex. METHODS: In this randomized trial, 46 patients with severe upper limb impairment in the subacute stage after ischemic stroke were randomly assigned to receive either high-frequency rTMS over the contralesional dorsal premotor cortex or low-frequency rTMS over the contralesional primary motor cortex. Low-frequency stimulation over the contralesional primary motor cortex served as an evidence-supported active comparator for poststroke upper limb motor recovery. Stimulation was administered five times per week for two weeks using magnetic resonance imaging-guided neuronavigation. All participants received concurrent standard rehabilitation therapy. The primary outcome was the Fugl-Meyer Assessment for Upper Extremity. Secondary outcomes included the Arm Subscore of the Motricity Index, the Hong Kong version of the Functional Test for the Hemiplegic Upper Extremity, the Modified Barthel Index, and resting-state functional magnetic resonance imaging-derived degree centrality. RESULTS: Both groups showed significant improvements in the primary and secondary behavioral measures (p < 0.01), with no significant between-group differences in the magnitude of change (p > 0.05). In neuroimaging analyses, patients receiving high-frequency rTMS over the contralesional dorsal premotor cortex showed significantly greater degree centrality changes in the ipsilesional middle occipital gyrus, contralesional medial superior frontal gyrus, and contralesional middle frontal gyrus than those receiving low-frequency rTMS over the contralesional primary motor cortex (p < 0.05). Within the high-frequency stimulation group, degree centrality changes in the ipsilesional middle occipital gyrus were positively correlated with improvements in the Fugl-Meyer Assessment for Upper Extremity (r = 0.619, false discovery rate-corrected p = 0.018). CONCLUSIONS: High-frequency rTMS over the contralesional dorsal premotor cortex produced behavioral improvements comparable to guideline-supported low-frequency rTMS over the contralesional primary motor cortex, without establishing superiority or formal non-inferiority. Exploratory neuroimaging analyses showed greater degree centrality changes in the ipsilesional middle occipital gyrus after high-frequency premotor stimulation, and these changes correlated with upper-limb motor improvement. These findings support further investigation of contralesional dorsal premotor cortex-targeted high-frequency rTMS for severe subacute post-stroke upper limb impairment. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR2000038049.

Humans↗

PubMed2026

Efficacy and safety of once-weekly semaglutide 2·4 mg in Chinese adults with overweight or obesity (STEP 12): a randomised, double-blind, placebo-controlled, multicentre, phase 3b trial.

BACKGROUND: Semaglutide 2·4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m2 or at least 27 kg/m2 and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2·4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds. METHODS: This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m2 and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m2, with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed. FINDINGS: Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66·5%) of 242 participants were randomly assigned to semaglutide 2·4 mg and 81 (33·5%) to placebo; 121 (50·0%) participants were female, and 47 (19·4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12·1% [SE 0·6] vs -2·2% [0·8]; estimated treatment difference -9·9 percentage points [95% CI -11·8 to -8·0]; p<0·0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80·5% vs 24·4%; odds ratio [OR] 14·8 [95% CI 7·4 to 29·6]; p<0·0001). Adverse events were reported in 141 (87·6%) of 161 participants in the semaglutide 2·4 mg group and 61 (75·3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common. INTERPRETATION: Semaglutide 2·4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide. FUNDING: Novo Nordisk A/S. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Adult↗

PubMed2026

Open Dialogue versus treatment as usual for adults presenting in crisis to mental health services in England (the ODDESSI Trial): a multisite cluster-randomised trial.

BACKGROUND: Open Dialogue is a person-centred, transdiagnostic model of mental health care that emphasises continuity, therapeutic relationships, and collaboration with the service user's social network. Open Dialogue is a service-wide approach to care involving network meetings with the service user, members of their social network, and usually two practitioners who support the network throughout the duration of care. In this cluster-randomised trial, we aimed to evaluate the clinical effectiveness of Open Dialogue versus treatment as usual for adults presenting in crisis to community mental health services in England. METHODS: This multicentre, parallel two-arm, cluster-randomised, controlled superiority trial was conducted in mental health services in five National Health Service trusts in London and the South of England. Clusters were defined at the level of primary care practices within service catchment areas. Participants were adults aged 18 years or older presenting in crisis to mental health services and registered with a practice within trial clusters. Randomisation was done at the cluster level (1:1), stratified by catchment area, and balanced on average general practice (GP) list size and Index of Multiple Deprivation (2015). The chief investigator, senior statistician, and assessors of the primary outcome were masked in the study. Participants either received Open Dialogue or treatment as usual, which refers to the functional team model currently implemented throughout English mental health services. The primary outcome was time (days) to first relapse following initial recovery from the index crisis censored at the end of the 2-year follow-up period. Participant-reported secondary outcomes were EuroQol Visual Analogue Scale, Social Provisions Scale, Lubben Social Network Scale, Questionnaire about the Process of Recovery, and the Client Satisfaction Questionnaire, measured at five timepoints over 2 years, and clinical measures were extracted from electronic health records. People with relevant lived experience were involved in the design and execution of the study. Fidelity to the model of care in Open Dialogue and treatment as usual, and adherence to the delivery of Open Dialogue, were measured prior to each site starting participant recruitment, then every 6 months thereafter until the final participant follow-up in that site. The trial was retrospectively registered (ISRCTN52653325) and is complete. FINDINGS: 185 general practices associated with six mental health Trusts across England were identified for screening. 105 practices were excluded, and 80 were included in cluster formation, forming 32 clusters that were randomly assigned (16 to treatment as usual and 16 to the Open Dialogue intervention). One mental health trust (two clusters) withdrew, resulting in five mental health trusts (30 clusters) participating in the trial. Between June 25, 2019, and Dec 9, 2021, 494 participants (266 [54%] female gender, 221 [45%] male gender, 341 [69%] White British) with a mean age of 38·1 years (SD 13·4) provided consent for study inclusion (223 in the treatment as usual group and 271 in the Open Dialogue group). Of these, 174 (78%) in the treatment as usual group and 225 (83%) in the Open Dialogue group recovered and had data enabling relapse determination; there was no significant difference between groups on the primary outcome of time to relapse following initial recovery (marginal hazard ratio 0·95 [95% CI 0·67-1·32]). For secondary outcomes, Open Dialogue was associated with significantly lower probabilities of psychiatric inpatient admission and re-referral to crisis care or secondary mental health services, and with improvements in self-rated recovery, health-related quality of life, and satisfaction with services. There were no significant differences in social network quality or size. There were 386 serious adverse events (281 in the treatment as usual group and 105 in the Open Dialogue group); 376 (97%) were deemed to be unrelated to the intervention. INTERPRETATION: Open Dialogue did not reduce time to first relapse compared with treatment as usual, the primary outcome, but it reduced acute inpatient bed use, improved service user reported outcomes and experience, and there were no significant safety concerns. Further investigation is required to determine whether Open Dialogue can enhance the effectiveness and acceptability of crisis care and continuing care in community mental health services. FUNDING: National Institute for Health Research.

Humans↗