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PubMed2026

Opioid-sparing anesthesia based on opioid-free principles for early recovery after total knee arthroplasty: A randomized controlled trial.

OBJECTIVE: To evaluate whether an opioid-sparing anesthesia strategy (OSA), based on opioid-free anesthesia (OFA), improves early postoperative recovery quality and optimizes functional outcomes after total knee arthroplasty (TKA), compared with conventional opioid-based anesthesia (OBA). DESIGN: A randomized controlled trial with blinding of patients, surgeons, and outcome assessors. SETTING: Single center, July 2025 to February 2026. PATIENTS: 98 adult patients scheduled for elective unilateral TKA. INTERVENTION: Patients were randomized to the OSA or OBA group. The OSA regimen used esketamine and dexmedetomidine as the primary analgesic backbone, whereas the OBA regimen was opioid-based. Both groups received preoperative femoral nerve block and were administered oxycodone at skin incision and closure. Postoperatively, both groups received the same multimodal analgesia and patient-controlled analgesia. MEASUREMENTS: The primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. Secondary outcomes included 48-h QoR-15; Oxford Knee Score (OKS) and EQ-5D-3L at 1 and 3 months; high pain at 1 month and chronic postsurgical pain at 3 months. Exploratory outcomes included postoperative C-reactive protein (CRP), and postoperative nausea and vomiting (PONV), among others. RESULTS: At 24 h postoperatively, QoR-15 was higher in the OSA group than in the OBA group (118.4 ± 11.5 vs 113.3 ± 12.2; adjusted difference 5.12, 95% CI 0.51-9.74; P = 0.029), and this advantage persisted at 48 h (adjusted difference 5.54, 95% CI 1.57-9.52; P = 0.007). The OSA group had a lower incidence of PONV (P = 0.025) and lower postoperative CRP levels (P = 0.001). At 1 month, OKS was higher in the OSA group (adjusted difference 2.31, 95% CI 0.34-4.27; P = 0.022), with no significant differences in other secondary outcomes. CONCLUSION: In TKA, this OFA-based OSA strategy improved early postoperative QoR-15 scores. However, the QoR-15 difference did not reach the minimal clinically important difference, so its clinical relevance remains uncertain.

Humans↗

PubMed2026

Evaluating the pathogenic significance of unique chromosomal variants in craniosynostosis using patient-derived induced pluripotent stem cells and mouse modelling.

PURPOSE: Unravelling causal links between unique structural/copy-number variants (SV/CNV) and associated phenotypes is essential for correct genetic counselling. We investigated two families in which patients with craniosynostosis had SV/CNV potentially dysregulating a fibroblast growth factor (FGF)-encoding gene; a 730 kb dup(4)(q21.21) including FGF5; and a complex 568 kb interspersed 13q12.11 duplication, located 841 kb from FGF9. METHODS: We combined bioinformatic predictions of altered topologically-associating domain (TAD) structure, with experimental analysis (RNA- and ATAC- [assay for transposase-accessible chromatin] sequencing) of patient induced pluripotent stem cell lines (iPSCs) differentiated to neural crest (NCC) and osteoprogenitor (OPC) identities. For the dup(4)(q21.21) we generated a mouse bearing an equivalent rearrangement using CRISPR-Cas9 targeting. RESULTS: TAD analysis suggested potential dysregulation of the FGF5/FGF9 gene by bringing it into a novel genomic milieu. The RNA- and ATAC-seq assays demonstrated FGF5/FGF9 upregulation (2.7-18x) and local opening of chromatin, in 3/4 cell lines. For the dup(4)(q21.21), a causal role was supported by the mouse model, whereas interpretation of the 13q12.11 SV is confounded by a co-existing FOXP2 pathogenic variant. CONCLUSION: Patient iPSC-differentiated NCC and OPC lines, combined with TAD-based modelling to generate testable functional hypotheses, provide valuable functional evidence when evaluating causation of unique SV/CNV in craniosynostosis.

copy-number variant↗

PubMed2026

An Assessment of Reliability Estimation Methods for Binomial Health Care Quality Measures.

We evaluated the performance of commonly used methods for estimating the reliability of binomial health care quality measures using simulated datasets spanning a range of performance score means and variances, numbers of entities, and patient sample sizes. For each simulation, reliability was estimated for all selected methods and compared with the known true reliability derived from the simulation parameters, with methods assessed on their accuracy and precision. Logistic regression with reliability estimated on the outcome scale demonstrated the highest accuracy and precision among all methods evaluated. The widely used Adams beta-binomial method performed poorly, although a modification recommended by Nieser and Harris substantially improved its performance. These approaches are applicable only to binomial measures. Among methods that can be applied to both binomial and continuous measures, permutation resampling of the Spearman rank correlation coefficient was the most accurate and precise, outperforming other commonly used approaches. Overall, for binomial quality measures, logistic regression on the outcome scale is the preferred method for reliability estimation, followed closely by the modified beta-binomial approach, while for non-binomial measures, permutation-based Spearman rank correlation appears to be the most suitable method.

Reproducibility of Results↗

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

Comparison of summative assessments between simulated electronic health records versus traditional paper-based patient cases: A non-inferiority randomized controlled trial.

INTRODUCTION: Electronic health records are fundamental to contemporary pharmacy practice, yet evidence supporting their use in pharmacy education is lacking. This single-center, non-inferiority randomized controlled trial with blinded outcome assessment evaluated whether delivering patient cases via a simulated academic EHR (aEHR) was non-inferior to a traditional paper-based format in student exam performance. METHODS: 53 third-year PharmD students at the University of British Columbia were randomized 1:1 to complete a mock summative examination using either the aEHR or paper-based case delivery, stratified by self-reported EHR comfort level. The primary outcome was mean written exam score (%). Non-inferiority was pre-specified at a margin of 14%. Adjusted linear regression was used for the primary analysis, with a multiple imputation sensitivity analysis. Student perceptions were explored through post-exam focus groups analyzed using inductive thematic analysis. RESULTS: 42 students (21 per group) completed the exam and were included in the primary analysis. Mean scores were 66% (SD 11) in the aEHR group and 68% (SD 10) in the paper group. The adjusted mean difference (paper minus aEHR) was -2.2% (95% CI -9.2% to +4.8%), satisfying non-inferiority but not superiority. Sensitivity analysis (n = 53) yielded consistent results (-2.3%; 95% CI -7.1% to +4.1%). Focus groups revealed initial student anxiety with the aEHR but recognized its alignment with clinical practice. DISCUSSION: These findings support the feasibility of integrating simulated EHRs into summative pharmacy assessments without compromising performance. CONCLUSION: Simulated EHRs are a non-inferior assessment medium compared with paper-based formats and represent a viable step toward technology-driven pharmacy practice environments.

Humans↗

PubMed2026

The Effect of Game-Based Virtual Reality Rehabilitation and Its Impact on Upper Extremity Function After Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

BACKGROUND: Arthroscopic rotator cuff repair (ARCR) often results in prolonged recovery and limited shoulder function. Conventional physical therapy rehabilitation programs require sustained patient engagement; however, adherence is frequently low. Game-based virtual reality (VR) offers an interactive and engaging environment that may enhance rehabilitation outcomes. OBJECTIVE: To evaluate the effect of a game-based VR program on the function of the upper limb in patients following ARCR. METHODS: A randomized controlled trial was conducted with patients who underwent ARCR. Participants were randomized into two groups: game-based VR or conventional rehabilitation. Outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand score, pain severity by the Numerical Pain Rating Scale, range of motion measures, and muscle strength testing. Assessments were performed at baseline and at 6 weeks and 12 weeks post surgery. RESULTS: Results have shown significant within-group improvements in pain, function, range of motion, and isometric muscle strength across all time points (P < 0.05). Between-group analysis revealed greater improvements in pain, function, flexion range, and abduction and external rotation strength in the experimental group at both time points (P < 0.05). Abduction range improved significantly only at 12 weeks (P = 0.02), whereas external rotation range showed no significant difference between groups at either time point (P > 0.05). CONCLUSION: The findings indicate that integrating game-based VR rehabilitation provides additional benefits over conventional therapy in improving pain and upper extremity function following ARCR. These findings support the use of VR as an effective alternative to the conventional rehabilitation for postoperative rehabilitation.

Humans↗

PubMed2026

A Pilot Study: Developing a Lactating Dairy Goat Model to Study Staphylococcus aureus Mastitis in Women.

INTRODUCTION: Lactational mastitis is common in lactating women, with Staphylococcus aureus as the most commonly isolated agent associated with infectious lactational mastitis. Currently, there are no evidence-based guidelines for antimicrobial treatment due to barriers in obtaining pharmacokinetic data from lactating women. To overcome this barrier, a suitable large animal model is needed. Goats are an ideal translational model for human mastitis due to their anatomical and physiological similarity to humans. The objective of this pilot study was to assess if goats would develop clinical mastitis following intramammary inoculation with a clinical human isolate of S. aureus with the goal of establishing an alternative in vivo model for future research. The hypothesis was that the infected mammary gland half would show similar clinical signs to women with mastitis and demonstrate a similar local immune response when compared to the control mammary gland half. METHODS: One half of the mammary gland of two healthy lactating does was inoculated with a clinical human isolate of S. aureus. The other half of the mammary gland was sham inoculated with sterile buffered saline. Physical examinations, mammary gland assessments, and sterile milk samples were collected every 12 hours post inoculation. At 96 hours post inoculation, the goats were euthanized, and the mammary glands were examined for pathological changes. RESULTS: Goats did not develop systemic signs of disease following inoculation. Focal infected mammary gland changes included warmth, swelling, redness, discoloration, and reduced milk production; the other mammary gland half remained normal throughout the study period. S. aureus was enumerated from only the infected mammary gland half. The microscopic findings of the infected half showed neutrophilic inflammation and cell necrosis consistent with acute mastitis. DISCUSSION: This pilot study demonstrated lactating does can develop clinical signs like those observed in women. Goats have the potential to be a promising animal model to study infectious lactational mastitis.

Animals↗

PubMed2026

Effects of aromatherapy on menopausal symptoms: a systematic review and meta-analysis.

BACKGROUND: The postmenopausal period presents a significant challenge to women's health, characterised by vasomotor, psychological, and sleep disturbances. This systematic review and meta-analysis synthesised evidence on aromatherapy for menopausal symptoms. METHODS: We searched Cochrane Library, Web of Science, ScienceDirect, PubMed, Scopus, SID, and Google Scholar until January 2, 2026. The protocol was registered (PROSPERO: CRD420261303084). Randomised controlled trials and quasi-experimental studies were included. The Cochrane Risk of Bias tool and GRADE approach were used for quality assessment and certainty of evidence. Meta-analyses were performed using RevMan 5.3. RESULTS: Of 4435 records, 21 articles from 17 studies (n = 1347) were included. Aromatherapy significantly improved sexual function (MD: 7.05, 95% CI: 3.64-10.45), sleep quality (MD: -3.95, 95% CI: -5.94 to -1.97), overall menopausal symptoms (SMD: -1.00, 95% CI: -1.43 to -0.58), vasomotor symptoms (SMD: -0.79, 95% CI: -1.11 to -0.47), physical symptoms (SMD: -0.78, 95% CI: -1.10 to -0.46), somatic symptoms (MD: -1.34, 95% CI: -2.46 to -0.23), psychological symptoms (SMD: -0.59, 95% CI: -0.96 to -0.23), anxiety (SMD: -0.63, 95% CI: -1.10 to -0.16), and depression (SMD: -0.57, 95% CI: -0.85 to -0.28). No significant effect was found for urogenital symptoms. GRADE certainty was 'Very Low' for sexual function and sleep quality, and 'Low' for other outcomes. CONCLUSIONS: Preliminary evidence suggests that aromatherapy may be a beneficial complementary therapy for alleviating some menopausal symptoms. However, given the substantial heterogeneity, methodological limitations, and limited number of studies for subgroup analyses, firm clinical recommendations cannot be made at this time. More rigorous, large-scale, multi-centre randomised controlled trials with standardised interventions and consistent adverse event reporting are required before definitive clinical recommendations can be made.

Humans↗

PubMed2026

Game-Based Intervention for Bullying: Assessing the Efficacy of the REThink Therapeutic Game in Primary School Children.

Children's mental health issues can have a lasting effect into adulthood, including enhanced risks for their social and emotional development, as well as their academic performance and overall behavior. Worldwide nearly 1 billion children are affected by the bullying phenomenon, with social, emotional, and economic consequences. In this vein, our study aimed to analyze the effect of the therapeutic game REThink on the improvement of emotion regulation abilities and the reduction of both bullying behavior and victimization in primary school children. Our sample consisted of 75 children who were voluntarily enrolled by their parents, and randomly assigned to the intervention group (n = 38) or to the control group (n = 37). They completed the baseline assessment consisting of emotion regulation, irrationality, bullying and victimization behavior measurements, then the children from the intervention group played the therapeutic game REThink. Four weeks later, after completing each level twice, every participant had completed the same questionnaires at the post-test assessment. The results indicated significant changes across victimization for children who were exposed to verbal, physical or social bullying, increased emotional control and lower levels of irrationality, low frustration tolerance to work and demandingness, with small to medium effect size improvements for the REThink game group compared to the control group. The REThink therapeutic game proved to be a promising intervention tool for reducing victimization effects and irrationality, and improving emotion regulation abilities in primary school children. Future research could improve on these results by addressing the timeline stability limit.

Humans↗

PubMed2026

Genomic epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli across humans, poultry and wastewater sectors in Douala, Cameroon.

BACKGROUND: The global health threat of antimicrobial resistance involves the human, animal and environmental sectors. Data from Cameroon are scarce. OBJECTIVES: This study aimed to define extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) rates and associated risk factors across the three sectors in Douala, Cameroon, and to define molecular characteristics of isolates. METHODS: From June 2022 to May 2023, we collected blood cultures from hospitalized patients, rectal swabs from healthy pregnant women, caeca from broiler chickens and environmental wastewater. Samples were screened for ESBL-Ec using CHROMAgar™ ESBL and cefotaxime-supplemented Tryptone Bile X-glucuronide agar. Antimicrobial susceptibility testing was performed by disk diffusion following EUCAST guidelines. Whole-genome sequencing was carried out using Illumina technology. RESULTS: Of 628 samples, 374 yielded ESBL-Ec. Prevalence was 54.6% (131/240) in pregnant women, 70.4% (169/240) in chickens and 93.1% (67/72) in wastewater. The proportion of ESBL-Ec among E. coli-positive-blood cultures was 9.2% (7/76). Multi-family household living was independently associated with ESBL-Ec carriage among pregnant women (adjusted odds ratio = 1.7, 95% CI 1.0-3.1, P = 0.03). High co-resistance (>70%) was observed for tetracycline, ciprofloxacin and trimethoprim/sulfamethoxazole. Sequencing of 32 isolates revealed 45 distinct resistance genes, including blaCTX-M-15 (n = 13, 40.6%), blaCTX-M-55 (n = 11, 34.4%) and last-resort antibiotic resistance genes mcr-1 and bla OXA-181. High-risk sequence types included ST131 (pregnant women) and ST10 (chickens). Notably, ST48 was shared between pregnant women and chickens, and ST155 between pregnant women and wastewater. CONCLUSION: Cross-sectoral ESBL-Ec in Douala exhibits high genomic diversity and alarming resistance. The occurrence of last-resort genes requires immediate One Health surveillance and coordinated interventions.

Journal Article↗

PubMed2026

Diagnostic performance of machine learning models versus established risk stratification for intracranial aneurysm rupture: a systematic review and bivariate meta-analysis.

BACKGROUND: Machine learning (ML) models have been proposed to improve the discrimination of intracranial aneurysm rupture status beyond established clinical risk stratification tools. However, reported performance is heterogeneous and the relative contribution of model architecture and feature dominance remains unclear. METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy systematic review and diagnostic meta-analysis of studies evaluating ML models for intracranial aneurysm rupture discrimination. PubMed, Embase and CENTRAL were searched to February 2026. Sensitivity and specificity were pooled using a bivariate random-effects model, with summary receiver operating characteristic curves generated across training, internal testing and external validation datasets. Models were compared with regression-based approaches and Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid haemorrhage, Site of aneurysm (PHASES) scores. Subgroup and meta-regression analyses explored associations between algorithm family and feature domain. RESULTS: Sixty-two retrospective cohorts (29 709 patients 209 models) met the inclusion criteria. In training datasets, pooled sensitivity and specificity for ML were 0.81 (95% CI 0.75 to 0.85) and 0.83 (0.80-0.86), with an area under the curve (AUC) of 0.878, exceeding PHASES (AUC 0.667). In testing datasets, ML retained higher discrimination (AUC 0.837) than regression models (0.806) and PHASES (0.646). In external validation, sensitivity was preserved (0.82), but specificity declined (0.66). Deep learning demonstrated the highest AUCs (training and testing). Incorporation of haemodynamic or radiomic features improved pooled discrimination relative to morphology alone. Evidence of small-study effects and mostly unclear Prediction Model Risk Of Bias Assessment Tool ratings were observed. CONCLUSIONS: ML approaches demonstrate higher pooled discrimination for aneurysm rupture status than conventional risk scores in retrospective datasets, but reduced external validation specificity and heterogeneity limit confidence for clinical translation. Prospective, externally validated, calibrated models are required before integration into routine cerebrovascular risk stratification.

Humans↗

PubMed2026

CT-Derived pelvic morphometry for preoperative risk assessment of recurrent unilateral inguinal hernia.

BACKGROUND: Recurrent inguinal hernia remains a significant challenge in abdominal wall surgery despite advances in mesh-based repair techniques and minimally invasive approaches. Although pelvic skeletal morphology has been implicated in inguinal hernia development, its association with recurrent disease remains incompletely understood. This study aimed to evaluate computed tomography (CT)-derived pelvic morphometric parameters and investigate their potential value in preoperative recurrence risk assessment. METHODS: This retrospective study included 251 male patients with preoperative abdominal CT examinations and complete clinical records who underwent elective inguinal hernia repair at a tertiary referral center. After applying the predefined eligibility criteria, 188 patients with unilateral inguinal hernias constituted the primary study cohort, including 162 primary and 26 recurrent unilateral hernias. The Radoievitch angle and Ami's line were measured independently by two blinded radiology residents using a standardized CT-based pelvic morphometric measurement protocol, and the mean values were used for analysis. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the association between pelvic morphometric parameters and recurrent inguinal hernia. RESULTS: Patients with recurrent unilateral inguinal hernias demonstrated significantly greater affected-side Ami's line measurements (8.27 ± 0.63 vs. 7.90 ± 0.71 cm, p = 0.014) and larger Radoievitch angles (40.68 ± 4.02° vs. 38.80 ± 3.68°, p = 0.018) than patients with primary unilateral hernias. Both the Radoievitch angle (OR 1.14, 95% CI 1.01-1.28, p = 0.033) and Ami's line (OR 2.26, 95% CI 1.14-4.49, p = 0.020) remained independently associated with recurrent inguinal hernia after adjustment for age and body mass index. ROC analysis demonstrated modest discriminatory performance (AUC 0.634 for the Radoievitch angle and 0.633 for Ami's line), while the multivariable model incorporating age, body mass index, and Ami's line showed slightly improved discrimination (AUC 0.655). CONCLUSION: CT-derived pelvic morphometric parameters were independently associated with recurrent unilateral inguinal hernia. Although their individual discriminatory performance was modest, standardized CT-based pelvimetry may serve as an objective adjunctive tool for individualized preoperative recurrence risk assessment in patients who already undergo CT imaging for unrelated clinical indications. Prospective multicenter studies are warranted to validate these findings and determine their clinical applicability.

Humans↗

PubMed2026

Exercise-induced chronic adaptations and pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in patients with depression: A systematic review and exploratory meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a leading cause of disability worldwide. Although exercise has been shown to alleviate depressive symptoms, potentially by affecting the body's inflammatory response, evidence in this area remains inconsistent. This study synthesized the most recent evidence from randomized controlled trials (RCTs) on the relationship between exercise-induced chronic adaptations and pro-inflammatory cytokine levels in patients with depression. METHODS: Eligible RCTs were identified from six electronic databases. Effect sizes were pooled using mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Two independent researchers assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: The review included 21 RCTs involving 1572 participants, six of which were included in the meta-analysis. No evidence of efficacy was observed for the chronic effects of exercise on the levels of the pro-inflammatory cytokines interleukin-1-beta (IL-1β) (MD = -0.01, 95% CI [-0.06, 0.04], p = 0.79), interleukin-6 (IL-6) (SMD = -0.30, 95% CI [-0.64, 0.04], p = 0.08), and tumor necrosis factor-alpha (TNF-α) (SMD = -0.18, 95% CI [-0.50, 0.14], p = 0.27) in patients with depression. However, the pooled results for certain markers were not robust. The certainty of evidence for each outcome was very low owing to inconsistency, indirectness, and imprecision. CONCLUSIONS: Evidence for exercise improving pro-inflammatory cytokine levels in patients with depression during the chronic phase remains exploratory and uncertain. Well-designed, adequately powered studies incorporating a broader range of immune biomarkers and dynamic multi-time-point assessments are urgently needed to determine whether exercise-induced chronic adaptations can modulate inflammatory pathways in depression.

Humans↗

PubMed2026

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n = 56) compared to Enriched Supportive Therapy (n = 43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group × time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans↗

PubMed2026

A multicenter randomized phase II/III trial of salvage treatment for refractory primary central nervous system lymphoma using tirabrutinib: JCOG2314 (ReSTART).

Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy. Patients refractory to high-dose methotrexate-based induction therapy have an extremely poor prognosis. Although whole-brain radiotherapy (WBRT) is the standard salvage treatment and provides potent tumor control, early functional deterioration and late neurocognitive toxicity remain major concerns. A phase I/II trial on relapsed or refractory PCNSL demonstrated favorable efficacy and tolerability of tirabrutinib, a second-generation selective Bruton's tyrosine kinase inhibitor. Tirabrutinib's oral administration has enabled outpatient management. However, its clinical value for induction-refractory PCNSL remains uncertain. We designed a multicenter, randomized phase II/III trial (JCOG2314) to assess the non-inferiority of tirabrutinib to WBRT in overall survival and its potential to reduce functional deterioration and cognitive impairment. A total of 94 patients from 49 institutions will be enrolled over 4 years. The trial has been registered in the Japan Registry of Clinical Trials (study number: jRCT1031250645).

Humans↗

PubMed2026

Effects of Digital Mental Health Screening Alone and With the Online MINDBODYSTRONG CBT-Based Program on Burnout, Depression, Anxiety, Healthy Behaviors, and Suicidal Ideation in at-Risk Nurses at 3- and 6-Months Post-Intervention: An RCT.

BACKGROUND: Burnout and mental distress among nurses are global public health epidemics that adversely affect nurse well-being and healthcare quality. Evidence-based, scalable mental health interventions are urgently needed. AIMS: To evaluate the 3- and 6-month outcomes of a randomized controlled trial (RCT) comparing a psychologically safe, digital mental health screening and referral program alone versus the same screening and referral program combined with the video-based online MINDBODYSTRONG (MBS) cognitive behavioral therapy (CBT)-based skills-building program among nurses at risk for mental distress. METHODS: 501 nurses were recruited from professional organizations and healthcare systems across the United States by email and randomized to either mental health screening and referral (standard care) or standard care plus the MBS cognitive behavioral skills-building intervention (the intervention). All study activities were conducted remotely. Follow-up surveys administered at 3- and 6-months assessed anxiety, depression, suicidal ideation, burnout, healthy lifestyle beliefs, and healthy lifestyle behaviors using valid and reliable scales. RESULTS: Compared with the screening and referral only group, participants in the intervention group had greater reductions in anxiety and depression and significantly greater increases in healthy lifestyle beliefs and behaviors at 3 and 6 months post-intervention. After controlling baseline risk, the intervention group had a lower risk of suicidal ideation than the screening and referral group at 3 months (relative risk ratio [RRR] = 0.717; 95% CI: 0.320-1.606) and 6 months (RRR = 0.329; 95% CI: 0.101-1.072). The intervention group also had a significantly lower risk of burnout at 6 months (RRR: 0.698, 95% CI: 0.528, 0.929, p = 0.012). Nurses who completed more MBS sessions had less suicidal ideation at 6 months and those who completed more MBS skills-building activities had less burnout at 3 and 6 months. LINKING ACTION TO EVIDENCE: Integrating psychologically safe mental health screening combined with the scalable online CBT-based intervention, MBS, can produce sustained improvements in burnout, mental health symptoms, including suicidality, and healthy lifestyle beliefs and behaviors among nurses experiencing mental distress.

Humans↗

PubMed2026

Variability in β-human chorionic gonadotropin concentrations following evacuation of a hydatidiform mole pregnancy: A retrospective cohort study from Vietnam.

BackgroundGestational trophoblastic disease refers to a group of tumors defined by abnormal trophoblastic proliferation. This disease produces a distinct tumor marker, beta-human chorionic gonadotropin, which can be useful for diagnosis and follow-up. The objective of this study was to investigate the variations in serum beta-human chorionic gonadotropin levels after uterine evacuation as well and the progression of gestational trophoblastic neoplasia.Materials and methodsThis retrospective cohort study was conducted at Tu Du Hospital, Vietnam, between January 2019 and December 2020. All patients diagnosed with molar pregnancy were analyzed retrospectively based on serial serum beta-human chorionic gonadotropin levels following uterine evacuation. Post-evacuation outcomes, including relapsed molar pregnancy and gestational trophoblastic neoplasia, were also monitored.ResultsWe enrolled 560 patients with molar pregnancy, including 298 with complete hydatidiform mole and 262 with partial hydatidiform mole. Severe symptoms were more common in those with complete hydatidiform mole. Over the follow-up period, 97 cases of gestational trophoblastic neoplasia were noted. The data show that the median time to gestational trophoblastic neoplasia diagnosis was 8.75 ± 4.41 (4-26) weeks. In terms of variations in the serum beta-human chorionic gonadotropin levels, the generalized estimating equation model showed a faster decline in the complete hydatidiform mole group than in the partial hydatidiform mole group. Similarly, regression in serum beta-human chorionic gonadotropin levels was significantly more rapid in patients who progressed to gestational trophoblastic neoplasia than in those with relapsed molar pregnancy (-11,593 vs. -20,651.22 and -12,946.26 vs. -46,329.23 mUI/mL, p < 0.001).ConclusionsSurveillance of serum beta-human chorionic gonadotropin levels remains essential for gestational trophoblastic neoplasia monitoring in patients with molar pregnancy following surgical evacuation. The post-evacuation serum beta-human chorionic gonadotropin level regression curve helps distinguish gestational trophoblastic neoplasia from hydatidiform moles. Further evidence is required to strengthen these findings.

Humans↗

PubMed2026

An automated geometric modeling framework in GATE for the design and optimization of high-sensitivity converging-beam SPECT collimators.

Objective.The trade-off between detection sensitivity and spatial resolution is a fundamental challenge in designing organ-dedicated Single-photon emission computed tomography (SPECT) collimators. While converging-hole geometries offer a solution, their optimization is often hindered by the lack of flexible computational tools capable of modeling large-scale, non-parallel hole arrays. This study aims to develop an automated geometric modeling framework to facilitate the design and evaluation of complex converging- and diverging-hole collimators within standard Monte Carlo environments.Approach.We developed a specialized modeling framework by implementing custom C++ classes and a vector-based alignment algorithm within GATE. This platform enables automated, orientation-consistent construction of large-scale converging arrays not natively supported by standard implementations. A high-sensitivity pure cone-beam collimator (CBC) was designed using this framework. The evaluation used hot-rod, disc, and Jaszczak phantoms for physical characterization, while XCAT and dedicated brain models were employed for clinical tasks, including cardiac, brain perfusion, and DaTscan SPECT simulations.Main results.The CBC achieved a nearly fourfold sensitivity increase compared to a conventional low-energy high-resolution parallel-hole collimator at a 20 cm radius of rotation, while maintaining comparable spatial resolution. Despite a 52.3% field of view reduction, the CBC yielded a 2.2-fold noise reduction (CV: 11.7% vs 25.9%) and mitigated partial volume effects via geometric magnification. XCAT and brain phantom simulations confirmed enhanced anatomical definition and contrast recovery in cardiac, perfusion, and DaTscan tasks.Significance.This work provides an efficient computational tool for rapid design space exploration of advanced collimator geometries. The results demonstrate that the proposed CBC design offers a significant sensitivity advantage, making it highly suitable for high-performance, small-volume clinical applications such as brain and cardiac molecular imaging.

Tomography, Emission-Computed, Single-Photon↗