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Enhanced fracture detection on radiographs with AI assistance for clinicians: a systematic review and meta-analysis.

BACKGROUND: Emergency radiographic interpretation for fractures is prone to missed or misdiagnoses. Artificial intelligence (AI) is expected to become a powerful tool to assist clinicians in fracture detection. PURPOSE: A systematic review and meta-analysis was performed to assess whether AI improves clinicians' ability to detect fractures on radiographs. MATERIALS AND METHODS: A literature search was conducted in PubMed, Web of Science, and Cochrane Library for studies published between January 1, 2010, and October 10, 2025. A meta-analysis of diagnostic accuracy studies was performed using a Summary Receiver Operating Characteristic (SROC) curve. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Subgroup analysis and meta-regression were conducted to explore potential sources of heterogeneity. RESULTS: A total of 26 studies were included . The pooled sensitivity of clinicians increased from 77% (95% CI: 72-81) to 87% (95% CI: 83-90) with AI assistance, while the pooled specificity improved from 88% (95% CI: 85-90) to 92% (95% CI: 89-94). The corresponding AUC values were 0.90 (95% CI: 0.87-0.92) before and 0.95 (95% CI: 0.93-0.97) after AI assistance. Eight studies were rated as high risk of bias. Subgroup analysis and meta-regression identified potential sources of heterogeneity, including fracture location, AI model type, high risk of bias, and reference standards. CONCLUSION: AI assistance significantly improves clinicians' diagnostic performance in detecting fractures on radiographs for extremity and trunk fractures.

Humans

Determinants of private health insurance uptake and its association with healthcare utilization in Gulf Cooperation Council countries: a systematic review.

All Gulf Cooperation Council (GCC) countries have a multi-payer healthcare system that comprises governmental health coverage (GHC), funded by the government, and private health insurance (PHI), mainly sponsored by employers and purchased by individuals. Both are expected to influence healthcare utilization and contribute to system efficiency and patient well-being. This systematic review explored the determinants of PHI uptake and its association with healthcare service utilization in the presence of GHC in GCC countries. We systematically searched CINAHL, PubMed, Scopus, Web of Science, and Cochrane Library for peer-reviewed studies published between January 2012 and October 2022. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklists for both quantitative and qualitative studies, following PRISMA guidelines. Twenty-six studies met the inclusion criteria. Determinants of PHI uptake were mapped to Andersen's Behavioral Model of Health Services Use (BMHSU) and categorized into (1) predisposing factors (sex, age, marital status, and education), (2) enabling factors (employment/income and health system-related factors such as access and perceived service quality), and (3) need factors (health status, including chronic noncommunicable diseases). PHI uptake was positively associated with being male, married, highly educated, employed with a high income, and having chronic diseases. PHI was positively associated with healthcare utilization, particularly routine check-ups, preventive services, and the use of prescribed medicines. In GCC countries, PHI uptake is influenced by sociodemographic and socioeconomic characteristics, health status, and perceived service quality. PHI is also associated with higher healthcare utilization, underlining the need for evidence-informed policies that enhance equity and expand coverage.

Humans

Childhood Economic Mobility and Systemic Inflammation Among Men Who Experienced Low Income in Toddlerhood: The Moderating Role of Trait Hostility.

OBJECTIVE: Childhood economic upward mobility (ie, increases in family income across childhood) may attenuate links between childhood poverty and systemic inflammation in adulthood, the extent of which may vary depending on inter-individual differences in personality characteristics, including hostility. METHODS: Men who experienced low income in toddlerhood (N=171) were followed prospectively into adulthood. Annual family income was collected 12 times when men were 1.5 to 17 years old. Men completed the Cook-Medley Hostility Scale and had their fasting blood drawn to measure circulating levels of C-reactive protein (CRP) at age 32. Multiple linear regression analyses examined main and moderation effects of childhood economic upward mobility and adult hostility on CRP levels adjusting for income at 1.5 years, race, parent educational attainment, and adult income, education, waist circumference, and smoking status. RESULTS: Main effects were nonsignificant, but an interaction effect emerged. Counter to expectations, childhood economic upward mobility related to greater adult CRP as trait hostility decreased ( β =-0.203, P =.018). Simple slope analyses further revealed that childhood economic upward mobility was positively associated with CRP among men lower in hostility ( β =0.23, SE=0.09, P =.020) but was unrelated to CRP among men higher in hostility. Results of post hoc sensitivity analyses are also discussed. CONCLUSIONS: Counterintuitive findings suggest that for men who experience poverty in toddlerhood, the association between childhood economic upward mobility and adult CRP may be nuanced and even in the positive direction for men low in hostility, which aligns with work on unintended health consequences of upward mobility.

Humans

Haemodialysis Nurses' Self-Reported Cultural Competence and Responsiveness: A Cross-Sectional Survey.

BACKGROUND: People receiving in-centre haemodialysis have distinct cultural care needs and preferences, and nurses are expected to respond to these. However, haemodialysis nurses' cultural competence and responsiveness are unknown. OBJECTIVES: To examine nurses' cultural competence and responsiveness when caring for people with diverse cultural characteristics. DESIGN: An online cross-sectional survey. PARTICIPANTS: Haemodialysis nurses from Australia and New Zealand (n = 123), recruited through the Renal Society of Australasia and professional networks. MEASUREMENTS: The 25-item Cultural Competence Assessment instrument measured cultural awareness and sensitivity, and culturally responsive behaviours. Demographic characteristics were also collected. RESULTS: Of 123 complete responses, overall cultural competence was high (M = 5.09, SD = 0.76), particularly awareness and sensitivity (M = 5.76, SD = 0.53), with significantly higher scores among those who had completed cultural awareness training (p = 0.009). In contrast, culturally responsive behaviours were moderate (M = 4.53, SD = 1.23), highlighting the gap between cultural competence and responsiveness. The lowest scoring areas were documentation of patients' cultural needs (M = 3.88, SD = 2.02) and access to cultural learning resources (M = 3.02, SD = 1.75), indicating limited supports. Qualitative findings reflected practices of culture care preservation and accommodation, with themes of cultural awareness and language differences highlighting barriers related to language and resources. CONCLUSIONS: High cultural competence does not necessarily translate into culturally responsive behaviour. Organisational supports, including guidance for documenting cultural needs, cultural assessment tools and accessible learning resources, may help strengthen culturally responsive haemodialysis care.

Humans

Indigenous body image amid rapid social and economic change: A reflexive thematic analysis of Wayuu narratives.

The Wayuu, Colombia's largest Indigenous group, are experiencing rapid social, economic, and technological change, including expanding internet access, educational opportunities, and increasing exposure to globalised media. Though the harmful effects of appearance-idealised media imagery on body image are well documented, indigenous body image research remains unevenly distributed across global contexts, with Latin American Indigenous communities particularly underrepresented. This study explored how Wayuu people understand and experience appearance ideals and body image in the context of expanding digital media exposure and rapid sociocultural and economic change. Five focus groups of up to 9 participants were conducted with 29 Wayuu participants (18-68 years; 23 women, 6 men). Using reflexive thematic analysis, three overarching themes were identified: (1) Intersecting sources of appearance pressure: encompassing influences from social media, Wayuu family expectations, and discrimination from non-Indigenous peers; (2) Negotiating and resisting appearance ideals: from body dissatisfaction and restrictive eating to affirmation of cultural identity as protection; and (3) The changing role of appearance in today's Wayuu culture: participants linked globalised appearance ideals to expanding educational opportunities, migration, digital connectivity, and broader socioeconomic transformations occurring within Wayuu territories. While exposure to global ideals fostered comparison and dissatisfaction, cultural pride and collective belonging appeared to buffer against internalised colonial values. Culturally grounded media literacy and education initiatives co-developed with Wayuu communities could foster critical reflection while strengthening heritage. These results highlight the need for decolonial, community-based approaches to body image research and intervention in Indigenous contexts.

Adolescent

Effects of cold-water immersion after rugby-specific training on endurance performance.

BACKGROUND: This study investigated whether whole-body cold-water immersion (CWI) following rugby-specific training influences endurance exercise performance 24 h later. METHODS: Eleven healthy male collegiate rugby players completed an incremental cycling test to determine peak oxygen uptake (V&#x307;O 2peak ) and time to exhaustion at baseline (Pre). One week later, participants performed a standardized rugby-specific training session consisting of warm-up, skill-based passing, contact drills, individual training (i.e., conversion kicking and scrummaging), and a bronco endurance test (total duration: 180 min), followed by one of two recovery interventions in a randomized order: 1) whole-body CWI for 8 min at 15 &#xb0;C (CWI) or 2) seated rest for 8 min (Control). Participants then performed the incremental cycling test 24 h after each intervention. RESULTS: Training load during the rugby-specific training, assessed using heart rate-based training load and blood lactate concentrations, did not differ between the trials. Time to exhaustion (485&#xb1;72 vs. 518&#xb1;77 s, P=0.107, d=0.45) and V&#x307;O 2peak did not differ between the Control and CWI trials, whereas the relative changes in these variables from Pre were greater in the CWI than in the Control trials (both P<0.05). Oxygen uptake, minute ventilation, and rating of perceived exertion during submaximal exercise were similar across the Pre, Control, and CWI trials. CONCLUSIONS: These results suggest that whole-body CWI following rugby-specific training may be associated with favorable changes in endurance exercise performance 24 h post-intervention compared with the control condition. However, the expectancy/placebo effect of water immersion on exercise performance could not be excluded.

Humans

Diagnostic performance of machine learning models for malignant and non-malignant pleural effusion: Systematic review and meta-analysis.

BACKGROUND: Accurately distinguishing malignant pleural effusion (MPE) from non-malignant pleural effusion is clinically important, but the generalisability and methodological quality of machine-learning (ML) models remain uncertain. METHODS: We searched eight databases to 23 April 2026. Diagnostic performance was pooled using random-effects and Reitsma bivariate models, and study quality was assessed using PROBAST+AI. RESULTS: Forty-two studies were included; 17 contributed to the AUC meta-analysis and 14 to the bivariate analysis. The pooled AUC was 0.90 (95&#xa0;% CI 0.85-0.94; 95&#xa0;% prediction interval 0.62-0.98), with sensitivity of 0.80 (95&#xa0;% CI 0.77-0.83) and specificity of 0.87 (95&#xa0;% CI 0.79-0.92). Only nine studies reported external, temporal or independent validation. Externally validated studies had a lower pooled AUC than studies without external validation (0.83 vs 0.92), with lower specificity observed in the two externally validated studies contributing sensitivity and specificity data. All 42 development assessments had high overall quality concerns, and all 42 model evaluations were judged at high risk of bias. CONCLUSIONS: ML models showed good apparent accuracy for distinguishing MPE from non-MPE, but the evidence was limited by substantial heterogeneity, high risk of bias and scarce external validation. The pooled estimates reflect the average performance of different selected models rather than the expected accuracy of a single clinical test. ML models should be regarded as adjuncts to existing diagnostic pathways until they are confirmed by rigorous multicentre prospective external validation and clinical-impact studies.

Humans

Foot exercise plus education versus brief advice for the treatment of plantar heel pain (FEET Trial): a feasibility randomised controlled trial.

BACKGROUND: Despite foot muscle strengthening being a target of exercise interventions for plantar heel pain (PHP) no study has measured foot muscle outcomes, and existing research is limited by a lack of control (no treatment) comparisons. OBJECTIVES: To determine the feasibility of conducting a randomised controlled trial and investigate the acceptability and credibility of comprehensive progressive foot exercise and education compared to brief advice for PHP. DESIGN: Randomised parallel group feasibility trial. METHOD: People with PHP were randomised (1:1 concealed allocation) to receive either foot exercise plus education or brief advice for twelve weeks. Primary outcomes included willingness to enrol, recruitment rate, adherence, logbook completion, dropout rate, early withdrawal reasons, adverse events, additional treatments sought, and credibility/expectancy. RESULTS: Twenty people with PHP (16 women; age 50&#x202f;&#xb1;&#x202f;9 years; body mass index&#x202f;=&#x202f;30.7&#x202f;&#xb1;&#x202f;4.6&#x202f;kg/m2) were recruited over 15 weeks (1.3 participants per week). Primary outcomes were willingness to enrol (80%), adherence (physiotherapy sessions attended: foot exercise plus education 85%, brief advice 100%; home exercise program: 62% daily sessions completed, 72% thrice weekly sessions completed), logbook completion (foot exercise plus education 75%, brief advice 90%), dropout rate (15%), and additional treatments sought (69%). There were no intervention-related adverse events, and credibility scores were higher for foot exercise plus education. CONCLUSIONS: This study confirms feasibility and acceptability of a protocol comparing foot exercise plus education with brief advice in individuals with PHP, generating key insights to inform future trial design.

Humans

Menopause in the All of Us Research Program: a descriptive summary of electronic health record and survey response across sociodemographic characteristics.

OBJECTIVES: Menopause is a significant physiological transition with implications for health outcomes (eg, cardiometabolic disease), yet gaps remain in understanding this transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age=40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between electronic health record (EHR) diagnosis codes and survey responses. METHODS: We analyzed menopause-related surveys, EHR diagnostic codes, and genomic data among ~396,000 AoURP female participants. We summarized menopause-related variables across data sources, evaluated overlap between survey, EHR, and genomic data sets, and described age distributions overall and across sociodemographic characteristics. RESULTS: Among ~396,000 females, survey responses captured ~193,000 menopause observations, nearly seven times more than EHR diagnoses (~28,000), suggesting under-ascertainment in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis reported menopause in the survey. Approximately 22,000 participants had overlapping menopause-related EHR, survey, and genomic data. Survey age patterns matched expectations, with participants predominantly <40 years reporting premenopausal status and those >60 years reporting postmenopausal status. A small subset with age >70 years (N&#x2248;1,700; 4%) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age 45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed across sociodemographic characteristics (eg, race and ancestry). CONCLUSIONS: These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP data.

Age

Glucocorticoid receptor antagonism in major depressive disorder with childhood trauma: a randomized controlled trial.

Childhood trauma (CT) is a key risk factor for major depressive disorder (MDD) onset and persistence. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie this link, and preclinical studies suggest glucocorticoid receptor (GR) antagonism can reverse early life stress effects. This study tested whether the GR antagonist mifepristone reduces depressive symptoms in adults with MDD and CT. The RESET-medication study was a randomized, double-blind, placebo-controlled trial evaluating a 7-day course of mifepristone (1200 mg/day) or placebo in 158 adults with MDD and CT, assessed at baseline, 1 week, 6 weeks (primary endpoint), 3 months, and 6 months. The primary outcome was depressive symptom severity (IDS-SR) at week 6; secondary outcomes included symptom severity at other timepoints, clinical response, remission, anxiety, sleep, stress, disability, and salivary cortisol. At week 6, depressive symptoms declined in both groups, with no significant difference between mifepristone and placebo (b=-0.25, d=-0.03, 95% CI [-0.42, 0.36], pnom=0.887), and no group differences were found for secondary outcomes. Morning and evening cortisol were significantly higher with mifepristone at week 1, consistent with GR antagonism, but not at week 6. Adverse events were more frequent with mifepristone; mild and severe events occurred significantly more often, while the proportion reporting at least one adverse event was numerically higher but not statistically significant (93.6%vs. 82.5%, &#x3c7;&#xb2;(1)=3.60, p=0.058). Mifepristone produced the expected endocrine response but did not lead to clinical improvements in individuals with MDD and CT compared to placebo.

Humans

RR-interval-based atrial fibrillation detection and burden estimation: cross-dataset validation and calibration-aware probability analysis.

Objective.Atrial fibrillation (AF) burden has become an increasingly important endpoint in long-duration rhythm monitoring, but reliable burden estimation requires more than accurate AF detection alone. In particular, when burden is derived by aggregating predicted AF probabilities over time, probability calibration may directly affect burden validity under external dataset shift.Approach.This study developed an interpretable-interval feature model for AF detection and evaluated it using record-wise cross-validation on a development cohort and independent cross-dataset external validation on public Holter electrocardiographic databases. Window-level performance was assessed using the area under the receiver operating characteristic curve (ROC-AUC), area under the precision-recall curve (PR-AUC), Brier score, expected calibration error (ECE), and calibration intercept and calibration slope. Recording-level AF burden was estimated using both probability-based and hard-label aggregation and evaluated using mean absolute error (MAE) and agreement analyses.Main results.The model showed high discrimination in both development and external evaluation, with external ROC-AUC ofand PR-AUC of. However, external calibration deteriorated despite preserved ranking performance, with Brier score of, ECE(15) of, calibration intercept of, and calibration slope of. In the external cohort, probability-based burden estimation preserved strong association with reference burden but showed weaker raw agreement than hard-label aggregation, with MAE ofversus, consistent with systematic probability underprediction. Repeated external recalibration across record-level splits substantially improved probability quality and probability-based burden estimation. Median probability-burden MAE decreased fromwithout recalibration toafter Platt recalibration andafter isotonic recalibration, while median ECE(15) decreased fromtoand, respectively.Significance.These findings indicate that-interval-based AF detection maintained strong ranking performance in the tested external cohort, but probability calibration should be evaluated explicitly when predicted probabilities are aggregated into AF-burden estimates.

Atrial Fibrillation

Outcomes of patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications.

OBJECTIVE: This post hoc analysis of the phase 3b JUMP trial evaluated addition of anemia-supporting medications to ruxolitinib in patients with myelofibrosis and anemia. METHODS: 101 patients with baseline hemoglobin <12.0&#x2009;g/dL initiated an erythropoiesis-stimulating agent (ESA) or danazol <3&#x2009;months post-enrollment and maintained ESA/danazol &#x2265;3&#x2009;months; 97% initiated ESAs. Patients enrolled in JUMP who had hemoglobin <12.0&#x2009;g/dL but did not initiate ESAs/danazol within 3 months were evaluated as an unmatched comparator. Total JUMP population data were also analyzed for spleen length (&#x2265;50% reduction from baseline) and symptom response (&#x2265;6.5-point improvement in FACT-Lym score). RESULTS: Baseline characteristics were similar to comparator JUMP patients (no ESAs/danazol within 3&#x2009;months, n&#x2009;=&#x2009;1242). Mean total daily ruxolitinib dose remained >25&#x2009;mg. Week 24 spleen length response was achieved by 37% of patients; 26% achieved symptom response, similar to the comparator population (28% and 26%, respectively) and comparable to the total JUMP population (N&#x2009;=&#x2009;2233). Outcomes were similar between the hemoglobin <12.0&#x2009;g/dL analysis population and patients with baseline hemoglobin <10.0&#x2009;g/dL (n&#x2009;=&#x2009;52). In all groups, hemoglobin levels increased after Week 4 following an expected initial decrease. DISCUSSION: This analysis suggests that patients treated with ruxolitinib and anemia-supporting care continued to receive optimal ruxolitinib dosing; spleen-length and symptom response rates in these patients were comparable to the overall JUMP population, the majority of whom did not have anemia. CONCLUSION: Results support use of anemia-supporting medications with ruxolitinib and may allow maintenance of ruxolitinib dose intensity in patients with myelofibrosis and anemia.

Humans

Suicidality risk of cancer caregivers: a systematic review and meta-analysis of observational studies.

BACKGROUND: The increase in the number of global cancer cases is expected to lead to a greater caregiving burden. However, few studies have investigated the risk of suicidality among cancer caregivers. OBJECTIVE: The aim of this systematic review was to explore the risk of suicidality among cancer caregivers. METHODS: For this systematic review, a comprehensive search of the PubMed, Embase, Cochrane, Web of Science databases, PsycINFO and Scopus databases was conducted from inception to 16 July 2025. A meta-analysis was performed to determine the odds ratios (ORs) for case-control and cross-sectional studies and the adjusted hazard ratios (aHRs) for cohort studies. RESULTS: Seven studies were included (four cohort studies, one case-control study and two cross-sectional studies), and 638,188 study subjects and 4,203,957 nonexposed subjects. The meta-analyses revealed that the ORs was 1.91 (95% confidence interval [CI]: 1.46-2.49) in the case-control study, cross-sectional studies, and one cohort study which reported ORs, and the aHRs was 1.32 (95% CI: 1.16-1.50) in the three cohort studies. Caregivers of patients with highly aggressive cancers had a greater risk of suicidality (aHR = 1.66; 95% CI: 1.48-1.86). Within the first 7&#x2009;years following a patient's cancer diagnosis, the risk of suicidality among caregivers remained elevated (aHR = 1.42; 95% CI: 1.04-1.94). CONCLUSION: The results indicate the need for both clinical and societal awareness to reduce the risk of suicidality among cancer caregivers, especially those with highly aggressive cancers. TRIAL REGISTRATION: Registered prospectively in PROSPERO (https://www.crd.york.ac.uk/prospero/) with the registration number (PROSPERO CRD420251011926) and date of registration(15/03/2025).

Humans

Transcriptomics reveals species-specific adaptive strategies to calorie restriction in two Argopecten scallops with distinct lifespans.

Calorie restriction (CR) is a well-established non-genetic intervention for lifespan extension in multiple model organisms. Seasonal food shortage in cold and temperate seas may mimic CR, inducing in bivalves a response similar to that in vertebrates and thereby prolonging life expectancy. However, the relationship and the mechanism underlying the food availability and lifespan in bivalves remain largely unexplored. Two closely related scallop species the short-lived warm-water Argopecten irradians (lifespan <2&#xa0;years) and the longer-lived cold-water Argopecten purpuratus (7-10&#xa0;years) provide an ideal comparative system to investigate species-specific adaptive strategies. In this study, we subjected both species to CR for 30 and 56&#xa0;days and performed comparative transcriptomic profiling, weighted gene co-expression network analysis (WGCNA), and physiological assays to elucidate their distinct molecular responses. Transcriptomic analysis revealed that A. purpuratus exhibited substantially more DEGs than A. irradians at both time points under CR, with both species showing downregulation of metabolic pathways but to different extents. A. irradians mounted an early nutrient-sensing response at 30&#xa0;days (IGF1R, PIK3R3, INSR suppression), indicating acute sensitivity to limitation; by contrast, A. purpuratus displayed delayed FoxO activation at 56&#xa0;days, along with its downstream effectors NFKBIA, CREB3L4, and SMAD4, suggesting a gradual adaptive program may link to its extended lifespan. WGCNA identified three negatively correlated modules in each species, with coral2 being the most prominent in A. irradians and darkolivegreen in A. purpuratus. The former was dominated by ciliary motility genes, whereas the latter featured coordinated repression of oxidative phosphorylation. Additionally, both species exhibited conserved suppression of mTOR/S6K growth signaling and activation of cellular maintenance programs. Collectively, these findings expand the understanding of CR-mediated longevity regulation in bivalves and provide candidate gene resources for future functional studies and breeding programs.

Pectinidae

Repetitive transcranial magnetic stimulation in substance use disorders is safe and tolerable: A Systematic review of 141 clinical trials including 4299 participants.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation intervention investigated as a treatment for substance use disorder (SUD) and its co-occurring disorders. As the number of rTMS SUD clinical trials increase, the safety and tolerability profile should be assessed. In this systematic review, we investigate adverse events (AEs) of rTMS in individuals with SUD and factors that may influence their occurrence. METHODS: We performed a systematic PubMed search to identify all controlled trials of rTMS in SUD published up to January 2025. Eligible studies were assessed, and safety information was extracted for analysis. RESULTS: A total of 141 clinical trials with 4299 participants were included in their active arms. rTMS trials recruited participants who were engaged in active substance use, were in the pre-treatment phase, in early recovery, or in sustained recovery. Twenty-two studies explicitly reported no AEs. Sixty-nine studies reported only mild AEs, while only six studies reported moderate AEs. Thirty-five studies did not report safety-outcomes/AEs. As expected, participants reported mild and temporary AEs such as headaches, pain or discomfort under the coil, or dizziness. Only nine studies reported serious AEs (7 studies in active TMS and 2 in sham TMS). Importantly, no seizures attributable to active rTMS were reported in these SUD samples. CONCLUSION: Overall, rTMS in SUD samples is safe and well-tolerated regardless of recovery stage and substance. Most reported side effects were mild, self-limiting, and tolerable. However, AE reporting was incomplete, as 35 of 141 trials reported no safety data, limiting conclusions to reported outcomes. This evidence supports the safety of rTMS as a potential stand-alone or adjunctive treatment for SUD.

Humans

Stretched penile length in boys with hypospadias: Population-based analysis using validated nomogram.

BACKGROUND: Hypospadias affects 1 in 200-300 male births. Parents are often concerned about penile adequacy beyond the urethral defect itself, yet few studies have systematically compared stretched penile length (SPL) in hypospadias against population-based reference standards. OBJECTIVE: To evaluate SPL distribution patterns in boys with Types I and II hypospadias and compare them with established normative data. METHODS: The authors studied 876 consecutive boys aged 1-14 years with unoperated Types I (distal) and II (mid-shaft) hypospadias. Two observers independently measured SPL using the validated SPLINT technique. The SPL measurements were compared against age-matched normative data from 1276 Indian children. Exact binomial probability tests were used for percentile distributions, chi-square tests for subtype comparisons and t-tests for mean deviations. RESULTS: The cohort included 479 Type I and 397 Type II cases. SPL distribution showed a marked leftward shift: 71% fell below the 50th percentile (expected 50%, p < 0.001) and 41.5% below the 25th percentile. Lower percentiles were overrepresented, 20.7% were below the 10th percentile and 20.8% in the 10th-25th range. Upper percentiles were depleted: only 7.4% in the 75th-90th range and 1.7% above the 90th percentile (all p < 0.001). Mean SPL was reduced by 6.8% (95% CI: -8.18 to -5.42%) in Type I and 7.5% (95% CI: -9.05 to -5.92%) in Type II. The two subtypes showed no significant distributional difference (&#x3c7;2 = 6.22, p = 0.18), suggesting that meatal position does not predict SPL reduction. CONCLUSIONS: Boys with distal and mid-shaft hypospadias show clinically meaningful SPL reduction that follows a continuous distribution rather than an all-or-none pattern. SPL reduction appears independent of meatal position. These findings support routine SPL assessment using population-specific references and can guide preoperative counselling.

Humans

Vegan multinutrient supplementation significantly increases Omega-3 index and 25-OH-vitamin D status: a randomized, double-blind, placebo-controlled trial in healthy young vegans.

In this randomized, double-blind, placebo-controlled trial, 72 healthy vegan adults (aged 19-57 years) received a multinutrient supplement consisting of a vitamin and mineral supplement (providing 26 &#xb5;g vitamin D) and an omega-3 supplement administered in either a single dose (EPA 98.7 mg, DHA 171.0 mg, additional vitamin D 36 &#xb5;g, vitamin E 3.7 mg) or a double dose (EPA 197.4 mg, DHA 342.0 mg, additional vitamin D 72 &#xb5;g, vitamin E 7.4 mg) or placebo capsules for 4 months. Nutrient biomarkers were assessed at baseline and at the end of the intervention after 4 months. An analysis of covariance was employed to test for between-group differences (p < 0.05) and adjusted for multiple testing using the Bonferroni-Holm method. Compared to the control group, which showed on average a significant decline in both the omega-3-index and 25-hydroxyvitamin D, participants in both intervention groups demonstrated significant increase in these parameters (p < 0.001). Although the double dose group exhibited numerically greater increases in omega-3 index and vitamin D compared to the simple dose group, the differences between these dosing regimens were not statistically significant. As expected, vitamin E levels remained unchanged, reflecting its inclusion solely for antioxidative protection in the omega-3 supplement rather than as a critical nutrient in vegan diets. In conclusion, supplementation significantly improved omega-3 and vitamin D status in healthy vegans, with no significant benefit from doubling the dose. Although clinical endpoints were not evaluated, improved nutrient status may have potential implications for health. The study has been registered at the German Clinical Trials Register (DRKS00028151).

Humans

Incidence of Cirrhosis in Fibrotic Metabolic Dysfunction-Associated Steatohepatitis: A Meta-Analysis of Placebo Arms from Randomized Clinical Trials.

BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cirrhosis (F4) in this group remain limited. We aimed to evaluate the incidence of cirrhosis in placebo-treated patients with fibrotic MASH in randomized controlled trials (RCTs). METHODS: In this single-arm meta-analysis, we systematically searched PubMed and Cochrane Library from inception to December 13, 2024, for pharmacological Phase&#x2009;&#x2265;&#x2009;2 RCTs reporting cirrhosis events (detected in liver biopsy or clinical signs) among patients with fibrotic MASH receiving placebo. Incidence rates were pooled using generalized linear mixed models with Clopper-Pearson confidence intervals (CIs). RESULTS: We identified a total of 11 RCTs, including 586 patients with fibrotic MASH. Total follow-up was 657.23 person-years (PYs), with 83 cirrhosis events reported. The pooled incidence rate was 13.09 per 100 PYs (95% CI 7.81 to 21.12, I2&#x2009;=&#x2009;75.6%, &#x3c4;2&#x2009;=&#x2009;0.682). In subgroup analysis, the incidence of cirrhosis was 3.40 per 100 PYs in MASH F2 (95% CI 1.10 to 10.02, I2&#x2009;=&#x2009;0%, &#x3c4;2&#x2009;=&#x2009;0) and 17.90 per 100 PYs (95% CI 10.63 to 28.55, I2&#x2009;=&#x2009;70.2%, &#x3c4;2&#x2009;=&#x2009;0.561) in MASH F3, with significant differences between stages (p&#x2009;=&#x2009;0.006). Sensitivity analyses showed consistent estimates. Most RCTs were judged to have a low risk of bias. CONCLUSIONS: This study provides stage-specific data on cirrhosis incidence in fibrotic MASH, highlighting the high short-term risk associated with MASH F3 in trial settings. These data may inform benchmarks to guide event expectations, enrichment strategies, sample size assumptions, and the interpretation of future MASH clinical trials.

Humans