Tag: nevin manimala

Adv Ther. 2026 Jul 28. doi: 10.1007/s12325-026-03707-z. Online ahead of print.

ABSTRACT

INTRODUCTION: To date, no head-to-head comparisons of apalutamide versus darolutamide have been reported for metastatic castration-sensitive prostate cancer (mCSPC). This study compared prostate-specific antigen decline ≥ 90% (PSA90) and overall survival (OS) between apalutamide and darolutamide, both without docetaxel, among patients with mCSPC in real-world clinical practice in the USA.

METHODS: Men diagnosed with mCSPC who initiated apalutamide or darolutamide between 2022 and 2025 were identified from linked electronic medical records and insurance claims. The apalutamide and darolutamide cohorts were balanced using inverse probability of treatment weighting. PSA90 response was assessed on-treatment. The proportions of patients achieving a PSA90 response and OS through a maximum of 6 months and 24 months post-treatment initiation, respectively, were compared between the two cohorts using weighted Kaplan-Meier and weighted Cox proportional hazards models.

RESULTS: For PSA90 analyses, weighted characteristics were well balanced between the apalutamide (n = 714; mean age 73.9 years, 59.6% White, 21.2% Black, 13.7% other, 5.5% unknown race) and darolutamide cohorts (n = 145; mean age 74.3 years, 58.8% White, 21.6% Black, 15.0% other, 4.7% unknown race). PSA90 response rates through 6 months were 49% higher for apalutamide than for darolutamide (weighted hazard ratio [HR]: 1.49 [95% confidence interval (CI) 1.07, 2.07]; p = 0.017). For OS analyses, weighted characteristics were also well balanced between apalutamide (n = 1460; mean age 73.5 years, 59.6% White, 21.5% Black, 13.5% other, 5.4% unknown race) and darolutamide (n = 287; mean age 73.7 years, 60.0% White, 22.4% Black, 12.4% other, 5.2% unknown race). Apalutamide was associated with a 51% lower rate of mortality relative to darolutamide through 24 months (weighted HR: 0.49 [95% CI 0.30, 0.83]; p = 0.007).

CONCLUSION: Among patients with mCSPC treated without docetaxel, apalutamide was associated with higher PSA90 response rates and lower mortality than darolutamide. These findings indicate a potential difference in disease control and survival between the two androgen receptor-targeted agents in routine clinical practice.

PMID:42518140 | DOI:10.1007/s12325-026-03707-z

Adv Ther. 2026 Jul 28. doi: 10.1007/s12325-026-03719-9. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to evaluate the effectiveness and safety of vosoritide in Chinese children with achondroplasia (ACH) in a real-world setting.

METHODS: A total of 26 children diagnosed with ACH and treated with vosoritide were enrolled in the study. Clinical indicators such as height, sitting height, and body mass index (BMI), as well as laboratory indicators including bone age and insulin-like growth factor level, were collected and analyzed before and after treatment. Improvements in height standard deviation score (SDS), sitting height/height ratio, and BMI were evaluated. Statistical differences were analyzed across different age and sex groups. Adverse reactions during the treatment were also monitored.

RESULTS: Among the 17 patients assessed at 12 months, height SDS (based on general population growth charts) improved from – 4.7 ± 0.1 at baseline to – 4.3 ± 0.2 at 12 months (P < 0.001). With continued treatment, annual growth velocity (AGV) significantly increased, reaching 8.7 ± 1.4 cm/year in 12 patients who remained under follow-up after 18 months of treatment. Furthermore, BMI SDS exhibited a continuous decline. The sitting height/height ratio decreased during the treatment, indicating an optimization of body proportions. Additionally, growth improvement was found in both age (below five years old and above five years old) and sex (male and female) groups. Except for the total procollagen I intact N-terminal (TP1NP), which significantly increased at 12 months of treatment compared to baseline, other biochemical indicators (including insulin-like growth factor, alkaline phosphatase, and osteocalcin) showed no significant differences after the treatment.

CONCLUSION: Vosoritide exerts significant growth-promoting effects and favorable safety in Chinese children with ACH. It improves height SDS and body proportions, demonstrating consistent effectiveness across various age groups and sex groups. Early diagnosis and timely initiation of vosoritide treatment can significantly alter the growth trajectory of these children.

PMID:42518139 | DOI:10.1007/s12325-026-03719-9

Prev Sci. 2026 Jul 28. doi: 10.1007/s11121-026-01959-3. Online ahead of print.

ABSTRACT

Suicide remains a significant public health issue in corrections settings in the United States, requiring systems-focused strategies for prevention and policy. We aggregated across 37 suicide rates, structural, social, and corrections-related variables from publicly available data sources. We used Latent Profile Analysis to identify clusters by profiles of correction systems across 50 states. We analyzed descriptive statistics of state characteristics by cluster to better understand their profiles. Lastly, we conducted ANOVAs to examine differences in suicide rates between clusters. We identified four clusters of states based on their profiles of corrections variables: number of facilities, populations in prisons, jails, and private prisons, prison overcrowding, prisoner-to-staff ratios, and disparities by race/ethnicity and gender. Thirteen states showed the highest racial and gender disparities in prison populations. Twenty-eight states showed average scores across all variables. Four states showed the highest proportion of people incarcerated in privately owned facilities. Five states showed the highest incarceration rates in both prisons and jails. Significant differences in suicide rates were observed across clusters, especially within jails. Findings from this study enhance our understanding of how structural and social factors may be associated with suicide in corrections settings. The discussion includes specific, tailored prevention strategies and policy solutions aimed at systems-level intervention.

PMID:42518125 | DOI:10.1007/s11121-026-01959-3

Addiction. 2026 Jul 28. doi: 10.1111/add.70558. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Amid ongoing debate on whether low-to-moderate alcohol consumption reduces cardiovascular risk, studies examining the association between alcohol consumption and cognitive function have reported inconsistent results. To quantitatively assess this association, we conducted a dose-response meta-analysis of cohort studies, including stratified analyses by potential modifiers and study-level characteristics.

METHODS: Eligible studies were identified by searching PubMed, Embase and Web of Science for articles published through 13 June 2025. Studies investigating major cognitive impairment were excluded. Pooled standardized mean differences (SMDs) were calculated using a random-effects model.

RESULTS: We identified 20 studies including 78 657 participants. A weak inverted J-shaped association between alcohol consumption and cognitive function was observed, but the test for nonlinearity did not reach statistical significance (P for nonlinearity = 0.06). Compared with no alcohol consumption, heavy alcohol consumption (≥67 g/day) was inversely associated with cognitive function [SMD at 67 g/day = -0.18, 95% confidence interval (CI) = -0.36 to -0.00; 20 studies, 78 657 participants], while the evidence for a protective effect of low-to-moderate alcohol intake remained uncertain. In studies that accounted for baseline cognition, alcohol consumption of ≥28 g/day was associated with lower cognitive function (SMD at 28 g/day = -0.08, 95% CI = -0.15 to -0.01; 9 studies, 23 385 participants), whereas the association remained uncertain in studies that did not account for baseline cognition (SMD at 28 g/day = 0.13, 95% CI = -0.05 to 0.32; 11 studies, 55 272 participants) (P for interaction < 0.01). By region, alcohol consumption of ≥33 g/day was associated with lower cognitive function in studies conducted in the United States (SMD at 33 g/day = -0.11, 95% CI = -0.22 to -0.01; 7 studies, 25 538 participants), whereas the association remained uncertain in studies conducted in Europe (SMD at 33 g/day = 0.07, 95% CI = -0.08 to 0.22; 10 studies, 44 235 participants) (P for interaction = 0.02).

CONCLUSIONS: A review of current evidence shows that heavy alcohol consumption (≥67 g/day) is inversely associated with cognitive function, while the evidence for a protective effect of low-to-moderate alcohol intake remains uncertain. The inverse association is stronger in studies that accounted for baseline cognition, with the alcohol intake threshold (~28 g/day) for lower cognitive function close to the drinking guideline limits, although these findings should be interpreted cautiously because of the limited number of studies.

PMID:42517285 | DOI:10.1111/add.70558

J Sleep Res. 2026 Jul 28:e70411. doi: 10.1111/jsr.70411. Online ahead of print.

ABSTRACT

Sleep-related and chronotype traits have been shown to impact health in observational studies. To identify whether these associations are potentially causal, we conducted phenome-wide Mendelian randomisation analyses of short sleep, insomnia symptoms, total sleep duration, long sleep, snoring, daytime sleepiness and morning chronotype with a broad range of health-related phenotypes. We assessed the association between the genetic predisposition to these traits and the occurrence of 702 health-related phenotypes, using summary statistics of the largest genome-wide association studies in European individuals. Results that were significant (multiple comparisons: False Discovery Rate) and valid (robust genetic instruments, unaffected by horizontal pleiotropy) were validated using data from the second largest European genome-wide association study. Genetically determined short sleep was associated with increased risks of attention-deficit/hyperactivity disorder and neuroticism, musculoskeletal conditions, asthma and gastroesophageal reflux and lower educational attainment. Genetically determined insomnia symptoms showed associations with increased risk of coronary artery disease, major depression and osteoarticular disease. Genetically determined long sleep was linked to higher risk of iron deficiency anaemia and lower bone mineral density. Genetic predisposition to snoring was associated with more falls, greater body mass and higher low-grade inflammation. Genetically determined morning chronotype was related to higher vitamin D levels and lower risk of irritable bowel syndrome. No associations were found for daytime sleepiness. Overall, these findings indicate that genetically determined short sleep duration and insomnia symptoms are associated with mental and neurological problems, cardiovascular disease and musculoskeletal disorders, suggesting a potentially preventive, causal role of healthy sleeping patterns on chronic disease.

PMID:42517234 | DOI:10.1111/jsr.70411

Circ Arrhythm Electrophysiol. 2026 Jul 28:e014755. doi: 10.1161/CIRCEP.125.014755. Online ahead of print.

ABSTRACT

BACKGROUND: Large left atrial volume (LAV) is a strong predictor of advanced left atrial substrate and is associated with less successful outcomes following pulmonary vein isolation (PVI) alone. Prespecified variables of the aMAZE trial were evaluated to access for the impact of LAV and left atrial appendage ligation on atrial fibrillation (AF) outcomes.

METHODS: The aMAZE trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02513797) was a multicenter, randomized-controlled study evaluating the effects of LAV on freedom from atrial arrhythmias (AA) following PVI-only compared with LARIAT and PVI (LARIAT+PVI). In total, 610 drug-refractory patients with nonparoxysmal AF were randomized 2:1 to LARIAT versus PVI alone. Freedom from AA was assessed 12 months postprocedure. LAV was independently assessed by a core laboratory from cardiac computed tomography performed before ablation.

RESULTS: There were 404 patients in the LARIAT+PVI group and 206 in the PVI-only group. Logistic regression performed within each subgroup for primary effectiveness with LAV demonstrated that the recurrence of AA after PVI was directly related to increasing LAV. Freedom from recurrence of AA in the LARIAT+PVI arm was independent and preserved irrespective of LAV. Similar results were seen with LAV index. A tercile analysis of early persistent AF (perAF) patients (AF >7 days and <6 months) and LARIAT+PVI in the highest (>148 cm³) LAV tercile showed statistically significant freedom from AA compared with PVI-only (69% versus 49%; P=0.02). Significant differences (P<0.04) between groups in the early perAF cohort began at an LAV of 130 cm³ and an LAV index of 65 cm³/m².

CONCLUSIONS: The correlation of LAV with PVI effectiveness in this study demonstrates that AA recurrence after PVI alone is directly related to increasing LAV. Freedom from AA after left atrial appendage ligation in addition to PVI is independent of increasing LAV, and left atrial appendage ligation may therefore provide an adjunctive benefit in patients with nonparoxysmal AF and enlarged LAV.

PMID:42517227 | DOI:10.1161/CIRCEP.125.014755

Circ Arrhythm Electrophysiol. 2026 Jul 28:e014785. doi: 10.1161/CIRCEP.125.014785. Online ahead of print.

ABSTRACT

BACKGROUND: Recent meta-analyses of randomized controlled trials have raised concerns that treatment with omega-3 fatty acids may increase the risk of atrial fibrillation (AF). However, these meta-analyses included at most 8 trials. The aim of this current meta-analysis was to expand the search by including other eligible omega-3 randomized controlled trials with AF incidence data, incorporating both published and unpublished data.

METHODS: Eligible studies were randomized controlled trials investigating daily doses of ≥500 mg/d of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Additional inclusion criteria included ≥12 months of treatment with EPA/DHA, participants ≥50 years of age, and, where possible, the absence of known AF/atrial flutter at baseline. The primary outcome was the occurrence of new-onset AF. Our primary hypothesis was that risk for AF would simultaneously depend on both omega-3 dose (above or below 1500 mg/d) and background cardiovascular disease risk status, and that their combined impact on AF risk would be synergistic.

RESULTS: A total of 35 randomized controlled trials (37 data sets; n=114 592) were included in this meta-analysis. Only studies including patients at high-risk for cardiovascular disease who were treated with high-doses of EPA/DHA (>1500 mg/d) showed a statistically significant increase in AF risk with a pooled odds ratio (OR) of 1.43 (95% CI, 1.14-1.79) and an absolute risk difference of 0.8% (0.40%-1.1%). None of the other 3 groups showed statistically significant levels of AF risk (odds ratios, 1.07 [high risk-low dose], 1.06 [low risk-low dose], and 1.03 [low risk-high dose]).

CONCLUSIONS: This meta-analysis suggests that high-dose EPA/DHA treatment is associated with an increased risk of AF in patients at high cardiovascular disease risk, whereas low-dose EPA/DHA does not appear to increase AF risk, even in high-risk populations. Further prospective studies are needed to evaluate any potential increased risk of higher doses balanced against potential benefits.

PMID:42517224 | DOI:10.1161/CIRCEP.125.014785

AIDS. 2026 Jul 28. doi: 10.1097/QAD.0000000000004588. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare maternal safety and pregnancy outcomes among women who did and did not use daily oral emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) for preexposure prophylaxis (PrEP) during pregnancy and postpartum.

DESIGN: Parallel cohort design, with follow-up from pregnancy to 6 months postpartum.

SETTING: Seven research clinics in Malawi, South Africa, Uganda, and Zimbabwe.

PARTICIPANTS: Three hundred fifty pregnant women aged 16-24 years at 32 weeks or less gestation, meeting local criteria for PrEP. At entry, PrEP initiators and decliners were enrolled 2 : 1. Participants could start or stop PrEP at any time.

MAIN OUTCOME MEASURES: Maternal adverse events were defined as grade ≥3 signs, symptoms, and diagnoses, and grade ≥2 chemistry abnormalities according to Division of AIDS toxicity tables. Adverse pregnancy outcomes included fetal loss, preterm birth, and small-for-gestational-age.

RESULTS: From March to December 2022, 350 eligible participants enrolled: 229 initiating and 121 declining PrEP at entry. Median duration of PrEP use was 34 weeks (interquartile range [IQR]: 16-40). Sixty maternal adverse events were reported over 230.3 person-years (incidence rate: 25.6, 95% confidence interval [95% CI]: 20.0-32.8). Although those on PrEP had higher rates of adverse events, this was not statistically significant (adjusted incidence rate ratio: 1.84, 95% CI: 0.53-6.30). Most frequent grade ≥3 adverse events were complications of pregnancy or delivery. Five (8%) were considered related to PrEP use. Among those with delivery information, 79 (24%) participants reported adverse pregnancy outcomes, with no differences between PrEP groups. No participants acquired HIV infections during follow-up.

CONCLUSION: Daily oral FTC-TDF remains a well tolerated and essential component of HIV prevention in pregnancy.

PMID:42517223 | DOI:10.1097/QAD.0000000000004588

Circulation. 2026 Jul 28. doi: 10.1161/CIRCULATIONAHA.126.079391. Online ahead of print.

ABSTRACT

BACKGROUND: Screening for atrial fibrillation (AF) on the basis of AF risk may be more effective. We aimed to develop, externally validate, and prospectively test a machine learning prediction model using electronic health records (EHRs) to guide AF screening.

METHODS: We developed and validated a random forest prediction model for new AF within 6 months, using age, sex, and 10 comorbidities (Future Innovations in Novel Detection of Atrial Fibrillation [FIND-AF] 2.0) in EHRs in the United Kingdom (n=2 081 139), Japan (n=7 795 244), Israel (n=2 166 795), Canada (n=627 919), and China (n=149 145). We conducted a prospective study where participants ≥30 years old without AF and with a CHA₂DS₂-VASc score ≥2 in men and ≥3 in women, stratified by FIND-AF 2.0 into high and low risk, undertook 4 ECG recordings per day for 3 weeks using a handheld ECG recorder, with a primary outcome of newly diagnosed AF. We estimated stroke risk associated with nonanticoagulated AF in patients with high FIND-AF 2.0 risk in the FinACAF (Finnish Anticoagulation in Atrial Fibrillation) registry of patients with AF (n=229 565).

RESULTS: FIND-AF 2.0 was applicable to all EHRs and showed good to excellent prediction performance (United Kingdom: area under the receiver operating characteristic curve [AUROC], 0.819 [95% CI, 0.809-0.829]; Israel: AUROC, 0.835 [95% CI, 0.828-0.842]; Japan: AUROC, 0.751 [95% CI, 0.745-0.757]; Canada: AUROC, 0.747 [95% CI, 0.741-0.753]; China: AUROC, 0.753 [95% CI, 0.725-0.771]), with AUROC>0.7 in men and women in all cohorts, and improved performance compared with CHA₂DS₂-VASc and C₂HEST. Of 1923 participants from 15 sites in the prospective study (mean age, 70.2 [SD 9.4] years), with a mean of 74.8 (SD, 19.4) ECG recordings, AF was diagnosed in 5 of 902 (0.6%) with low FIND-AF 2.0 risk and 46 of 1021 (4.5%) with high FIND-AF 2.0 risk (odds ratio, 8.46 [95% CI, 3.35-21.40], P<0.001). Median AF burden among high FIND-AF 2.0 risk-detected cases was 33.4% (interquartile range, 5.1%-91.6%), and 96.1% initiated oral anticoagulants. In the FinACAF registry, the rate of ischemic stroke for patients with high FIND-AF 2.0 risk, AF, and no anticoagulants was 6.0 events per 100 patient-years.

CONCLUSIONS: The EHR-based machine learning model, FIND-AF 2.0, identifies a high-risk subpopulation for AF diagnosis among patients at elevated risk of stroke and could enable scalable, EHR-driven, risk-guided AF screening.

PMID:42517218 | DOI:10.1161/CIRCULATIONAHA.126.079391

J Inj Violence Res. 2026 Jul 28;18(1). Online ahead of print.

ABSTRACT

BACKGROUND: This exploratory study aimed to describe characteristics associated with pediatric drowning and to examine the socioeconomic context, rather than to establish socioeconomic effects, by conducting a retrospective analysis at the sole tertiary facility with a pediatric intensive care unit in Okinawa Prefecture, Japan.

METHODS: Information from electronic medical records was collated for 75 drowning-related hospitalizations involving individuals aged less than 20 years at the Okinawa Prefectural Nanbu Medical Center and Children’s Medical Center from April 1, 2006, to May 31, 2021. Data on patient gender, drowning or hospitalization duration, drowning timing and settings, pre-existing medical conditions, and zip code were extracted from electronic medical records.

RESULTS: Among the 75 hospitalized patients, 64 were discharged without any morbidity, whereas 11 either perished or sustained severe morbidity. The submersion time (2.9 min, standard deviation [SD]: 4.6, in the no morbidity group vs. 44.1 min, SD: 87.0 in the severe group) and length of stay (4.1 days, SD: 3.7 vs. 46.4 days, SD: 64.9, respectively) were markedly extended in the severe group. Additionally, in patients under four years of age, drownings frequently occurred in bathrooms (p = 0.008), with incidents predominantly taking place between 17:00 and 23:00 (p = 0.021). Among hospitalized pediatric drowning patients, supervision was associated with lower odds of severe morbidity (odds ratio 0.17 (95% confidence interval 0.03-0.81)). This association persisted after adjustment for potential confounders such as the Area Deprivation Index and time of day. The interaction between supervision and the Area Deprivation Index was of borderline statistical significance (p = 0.050) and is considered hypothesis-generating.

CONCLUSIONS: Within this cohort of hospitalized pediatric drowning patients, the presence of supervision was associated with less severe outcomes. These exploratory findings highlight the potential value of preventive strategies tailored to regional attributes, but do not establish socioeconomic or causal effects.

PMID:42517211