Category: Nevin Manimala

Int J Neuropsychopharmacol. 2026 Mar 9:pyag009. doi: 10.1093/ijnp/pyag009. Online ahead of print.

ABSTRACT

IMPORTANCE: Seltorexant, a selective orexin-2 receptor (OX2R) antagonist, has demonstrated antidepressant effects in major depressive disorder (MDD), particularly among patients with higher baseline insomnia symptoms.

OBJECTIVE: To investigate flexibly dosed seltorexant vs flexibly dosed quetiapine extended release (quetiapine-XR) as adjunctive treatment to a selective serotonin (SSRI) or serotonin-norepinephrine (SNRI) reuptake inhibitor.

SETTING: Outpatient.

DESIGN: Randomized, active-controlled, multicenter, exploratory phase 2 study with screening (≤4 weeks), double-blind treatment (24 weeks), and post-treatment follow-up (2 weeks) phases.

PARTICIPANTS: Patients with MDD and inadequate response to 1-3 SSRIs/SNRIs, including an ongoing SSRI/SNRI, in the current depressive episode.

INTERVENTIONS: Flexibly dosed seltorexant (20 or 40 mg) or quetiapine-XR (150 or 300 mg, with 2-day initial dosing of 50 mg) once daily as adjunctive therapy to an SSRI/SNRI. Randomization (1:1) was stratified by baseline Insomnia Severity Index total score (≥15 vs <15). Safety, tolerability, and preliminary efficacy were evaluated.

MAIN OUTCOMES AND MEASURES: Primary efficacy endpoint was time to all-cause study drug discontinuation. Secondary efficacy endpoints included change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Subgroup analyses included MADRS change by mode dose (MD; most frequent daily dose received by a patient during the study). Safety and tolerability also were assessed.

RESULTS: Time to all-cause discontinuation (estimated 25th percentile [80% CI]: seltorexant, 62 [38, 83] days vs quetiapine-XR, 42 [35, 61] days; hazard ratio [80% CI]: 0.83 [0.6, 1.2]) and all-cause discontinuation (seltorexant, 41.2% vs quetiapine-XR, 47.1%; 2-sided p=.5355) did not differ significantly between treatment groups. For the seltorexant 20-mg MD group, MADRS total scores consistently improved over time and reductions were numerically greater at Weeks 18 and 24 versus the seltorexant 40-mg MD and the combined quetiapine-XR groups, and patients with higher baseline insomnia symptoms had greater improvement in MADRS total score, consistent with prior studies showing efficacy at 20 but not 40 mg (Savitz, et al. 2019; Mesens, et al. 2025). Treatment-emergent adverse event rates were 65.4% for seltorexant and 80.8% for quetiapine-XR.

CONCLUSIONS AND RELEVANCE: Results support the favorable tolerability and preliminary efficacy of seltorexant 20 mg daily as adjunctive treatment in patients with MDD, especially those with insomnia symptoms, and suggest potential approaches to differentiate seltorexant from quetiapine-XR in future adequately powered studies. Trial registration. Clinicaltrials.gov identifier: NCT03321526.

PMID:41795948 | DOI:10.1093/ijnp/pyag009

Fam Process. 2026 Mar;65(1):e70128. doi: 10.1111/famp.70128.

ABSTRACT

The purpose of this mixed methods study is to explore the impact of a culturally adapted parent-directed training program in the United States on 90 Latine parents’ perceptions of their child’s strengths and social functioning. In addition, the study aimed to investigate the impact of the program on Latine parents’ stress and their empowerment to advocate for their children. Participants were 90 Latine parents who participated in a 10-session culturally adapted training program. Quantitative analyses of pre-post data on the Family-Outcome Survey-Revised Scale, the stress subscale of the DASS-21, and Quality of Play Questionnaire indicated statistically significant improvements. Estimates of effect size and clinical significance were also measured. Analyses indicated clinically significant changes for some Latine parents. Approximately 1 out of 4 Latine parents reported clinically significant improvements (i.e., meaningful improvement) or improvements without clinical significance as related to advocacy for their child’s rights, and 1 out of 3 Latine parents reported clinically significant improvements or slight improvements in understanding their child’s strengths. Approximately 1 out of 3 Latine parents reported clinically significant improvements or slight improvements in reducing their stress symptoms, and approximately 1 out of 3 parents reported clinically significant improvements or slight improvements in their child’s social functioning. Our qualitative findings also revealed that participants (a) appreciated the role of parent leaders, (b) applied evidence-based strategies to help their children, and (c) connected with other parents to create a community. An implication for this study is that graduate programs need to continue to teach future practitioners how to engage in interdisciplinary and interprofessional work to provide effective services to culturally diverse populations.

PMID:41795938 | DOI:10.1111/famp.70128

Endocr J. 2026 Mar 7. doi: 10.1507/endocrj.EJ25-0437. Online ahead of print.

ABSTRACT

To explore the association between stress hyperglycemia ratio (SHR) levels and cognitive function in older patients with diabetes or prediabetes. Cognitive function was assessed through a composite Z-score, the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) subtest, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). SHR was calculated as the fasting blood glucose divided by the estimated average glucose from glycated hemoglobin. In subsequent analyses, SHR was divided into quartiles (quartiles 1 to 4), with the second quartile serving as the reference group. A weighted linear regression model was used to assess the association between SHR and cognitive function. After adjusting the corresponding covariates, the analysis revealed that compared to the second quartile, the first [β: -0.26; 95% confidence interval (CI): -0.39- -0.12], third (β: -0.13, 95% CI: -0.25- -0.02), and fourth (β: -0.21, 95% CI: -0.36- -0.06) quartiles were all associated with a decrease in Z-score. The first quartile was associated with a decline in AFT (β: -1.46, 95% CI: -2.57- -0.36). The first (β: -3.72, 95% CI: -6.06- -1.38) and fourth (β: -2.58, 95% CI: -4.98- -0.17) quartiles were associated with a decline in DSST. No statistically significant associations were observed between any of the quartile groups and CERAD (all p > 0.05). Both higher and lower SHR were associated with poorer overall cognitive function, with higher and lower SHR being related to worse memory dimensions, while lower SHR was associated with impaired executive function.

PMID:41795936 | DOI:10.1507/endocrj.EJ25-0437

Circ J. 2026 Mar 7. doi: 10.1253/circj.CJ-25-0889. Online ahead of print.

ABSTRACT

BACKGROUND: Because the prognostic value of lipoprotein(a) [Lp(a)] levels in Japanese patients remains unclear, we assessed their distribution and association with long-term outcomes in ST-segment elevation myocardial infarction (STEMI).

METHODS AND RESULTS: In our retrospective analysis of 868 consecutive patients with STEMI, the median serum Lp(a) level was 15.75 mg/dL at admission, and the median follow-up was 736.5 days. Using restricted cubic spline analysis, we stratified patients into high (≥47.26 mg/dL) and low (<47.26 mg/dL) Lp(a) groups. The high Lp(a) group had a higher proportion of older and female patients, with lower body weight, estimated glomerular filtration rate, and stent use, and higher dyslipidemia prevalence than those in the low Lp(a) group. The 5-year cumulative incidence of the composite primary endpoint (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or any revascularization) was significantly higher in the high Lp(a) group, primarily because of a high rate of any revascularization. Patients with elevated Lp(a) levels demonstrated higher rates of any revascularization for both de novo and restenotic lesions than those with lower levels. After adjusting for confounders, a high Lp(a) level was identified as an independent predictor of the primary endpoint (hazard ratio:1.932; 95% confidence interval:1.255-2.974).

CONCLUSIONS: In Japanese patients with STEMI, elevated Lp(a) levels were independently associated with worse long-term outcomes.

PMID:41795930 | DOI:10.1253/circj.CJ-25-0889

Environ Health Prev Med. 2026;31:17. doi: 10.1265/ehpm.25-00403.

ABSTRACT

BACKGROUND: Exposure to microplastics (MPs) can have adverse gastrointestinal effects by inducing inflammation and oxidative stress. The types of MPs in stool vary with the dietary intake. However, how MPs in the intestinal tract influence the inflammatory cytokine levels in the gastrointestinal tract in healthy individuals remains unclear, particularly in Japan, characterized by a high intake of vegetables and seafood. In this study, we investigated the relationship between food intake, stool MPs, and inflammatory markers in healthy Japanese individuals, and estimated the sources of the stool MPs.

METHODS: Twenty-two participants completed a questionnaire on daily food intake for 7 days. Thereafter, stool samples were collected to examine MP density via Fourier-transform infrared spectrophotometry. On day 8, blood samples were collected and analyzed for serum oxidative stress markers and cytokine levels. Next, the effect of total stool MP particle density (Low vs. High) on oxidative stress markers and cytokines levels was analyzed.

RESULTS: The median total MP particle density of the participants (median age: 44 years) was 7.20 MP particles per g of stool. Seafood intake was higher in the High MP group than in the Low MP group, with a Mann-Whitney U test yielding p = 0.035 for seafood intake. However, after the false discovery rate (FDR) correction, this effect was not significant. Nevertheless, the effect size for seafood intake was large, suggesting an association with MP level. Relative to the Low MP group, the High MP group showed significantly higher thymic stromal lymphopoietin (TSLP) levels (odds ratio: 13.5; 95% confidence interval: 0.99-183, p = 0.050). The analysis further revealed that the seafood consumed by the High MP group contained significant amounts of polyethylene (PE) and polypropylene (PP), MPs commonly used in plastic packaging (PE, p = 0.028; PP, p = 0.053).

CONCLUSION: This study showed that stool MP particle density is likely associated with seafood intake and the TSLP level, implying that excessive MP intake may adversely affect human health. Therefore, measures to reduce MP exposure are urgently required.

PMID:41795929 | DOI:10.1265/ehpm.25-00403

J Epidemiol. 2026 Mar 7. doi: 10.2188/jea.JE20250668. Online ahead of print.

ABSTRACT

Age-standardization is a key statistical method used in health statistics to adjust rates such as mortality or incidence, enabling comparisons across populations or time points with different age structures. This review traces its historical development, global and country-specific practices, and future directions. The method dates back to the 19th century, with major adoption in the 20th century through the Segi and Doll’s World Standard Population. While the World Health Organization (WHO) introduced an updated standard in 2000, the International Agency for Research on Cancer (IARC) continues to use the Segi and Doll’s standard in the Cancer Incidence in Five Continents series, prioritizing consistency and comparability in long-term cancer surveillance. Case studies from the IARC, the United States (U.S.), Japan, and the Republic of Korea (Korea) illustrate different responses to changing demographics. The U.S. adopted the 2000 standard with expanded age detail for the elderly population. Japan introduced the 2015 Japan Standard Population to account for its rapidly aging society, though regional data limitations presented challenges. Korea, experiencing one of the fastest aging transitions globally, updated to a 2020 standard for more accurate national and sub-national reporting. The review also emphasizes that age-standardization can obscure important age-specific trends. Methods like Joinpoint clustering help detect divergent trends by age groups. Looking forward, age-standardization remains essential amid global demographic shifts. However, updates of standard populations must balance improved relevance with the need for continuity and robust data. International coordination and digital tools will support more flexible and transparent health statistics in the future.

PMID:41795926 | DOI:10.2188/jea.JE20250668

Eur J Heart Fail. 2026 Mar 6:xuag066. doi: 10.1093/ejhf/xuag066. Online ahead of print.

NO ABSTRACT

PMID:41795868 | DOI:10.1093/ejhf/xuag066

Respir Med. 2026 Mar 5:108753. doi: 10.1016/j.rmed.2026.108753. Online ahead of print.

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) and asthma due to house dust mite (HDM) are increasing in children worldwide, including Indonesia, where the tropical environment favors HDM proliferation. Although Subcutaneous immunotherapy (SCIT) is widely used, local pediatric evidence remains limited.

OBJECTIVE: To evaluate the effect of HDM SCIT on clinical and immunological outcomes in children with AR and AR plus asthma.

METHODS: A double-blind randomized controlled trial was conducted in 41 children, divided into AR (n=20) and AR+asthma (n=21) groups. Participants received weekly HDM SCIT for 14 weeks. Total IgE, specific IgE, IL-10, TGF-β1, Combined Symptom Medication Score (CSMS), and Visual Analogue Scale (VAS) were measured before and after treatment. Statistical analyses included paired t-test, Wilcoxon, independent t-test, and Mann-Whitney, with significance at p<0.05.

RESULTS: HDM SCIT significantly reduced total IgE, TGF-β1, CSMS, and VAS (p<0.05). Specific IgE showed a downward trend without statistical significance. IL-10 levels slightly increased but were not significant (p=0.683). No significant differences in treatment effect were observed between AR and AR+asthma groups (p>0.05).

CONCLUSION: HDM SCIT improved clinical outcomes and reduced key immunological markers in children with AR and AR plus asthma, though no intergroup differences were found. These findings provide preliminary evidence supporting HDM SCIT as a safe and beneficial adjunct therapy in Indonesian pediatric populations.

PMID:41795860 | DOI:10.1016/j.rmed.2026.108753

Dermatology. 2026 Mar 8:1-13. doi: 10.1159/000551368. Online ahead of print.

ABSTRACT

Introduction Seborrheic keratoses (SK) are common benign epidermal tumors. Their pathogenesis is unknown, and no pathological significance is ascribed to them, although they could be part of paraneoplastic syndromes, in addition to presenting a variety of somatic mutations. SKs are associated with increased age, family history and sun-exposure. Methods This study aimed to analyze if SK was related to DNA repair genes polymorphisms and analyze if any epidemiological, clinical or environmental characteristics could modify their prevalence. It was conducted an epidemiological, analytical, observational, cross-sectional, retrospective case-control study. Both univariate and multivariate logistic regression models were used to evaluate which characteristics were associated with having >50 SKs versus <10. Results A total of 294 patients with melanoma were studied, 270 (91.8%) having had less than 10 SKs, while 24 (8.2%) >50. Of all the polymorphisms studied, only rs25487 in XRCC1 reached statistical significance (OR=3.56; 95% CI 1.36-9.33; p=0.01). In addition, an increasing age (OR=1.07; 95% CI 1.03-1.11; p=0.001) and the phototype (III-V vs. I-II) (OR=0.28; 95% CI 0.12-0.68; P=0.005) were related to the presence of >50 SKs. Conclusion We identified that increasing age, having a phototype I-II and the existence of the rs25487 polymorphism could be associated with the occurrence of KS.

PMID:41795822 | DOI:10.1159/000551368

Neurol Res. 2026 Mar 8:1-10. doi: 10.1080/01616412.2026.2641139. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to evaluate the effect of serum cholinesterase (CHE) levels on early neurological deterioration (END) in patients with mild anterior circulation stroke.

METHODS: We conducted a retrospective case-control study in the Neurology Department of Jiangsu Taizhou People’s Hospital from July 2018 to June 2023. A total of 334 patients with mild anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] ≤5 points) admitted within 24 h were included. Patients were classified into an END group and a non-END group according to the occurrence of END, and binary logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) across serum CHE quintiles.

RESULTS: A statistically significant difference and a clear linear trend (p < 0.05) were identified after adjusting for multiple confounding factors, indicating a protective effect of elevated CHE levels against END. Age stratified analysis was limited by reduced sample sizes and insufficient statistical power to detect potential subgroup differences.

CONCLUSION: In this retrospective case-control study, the END group had a significantly higher incidence of atrial fibrillation (AF) and lower CHE levels than the non-END group. The findings indicate an inverse association between CHE levels and the risk of END.

PMID:41795817 | DOI:10.1080/01616412.2026.2641139