Tag: nevin manimala

JAMA Netw Open. 2025 Jul 1;8(7):e2519622. doi: 10.1001/jamanetworkopen.2025.19622.

ABSTRACT

IMPORTANCE: The association between grandchild care and dementia remains unclear, with previous studies yielding mixed results and unclear mechanisms.

OBJECTIVE: To examine the association between grandchild care and dementia odds and to explore the mediating roles of mobile telephone ownership, broadband internet access, and reduced loneliness.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the China Health and Retirement Longitudinal Study from 2013 to 2018. Data analysis was conducted from March 10, 2024, to April 20, 2025. Multistage, stratified, cluster sampling was used to recruit participants from 28 provinces across China. Data were collected through biennial, computer-assisted personal interviews. The analytic sample comprised Chinese adults aged 50 to 79 years who were dementia free at baseline.

EXPOSURE: Grandchild caregiving was classified into 4 groups: noncaregivers (0 hours per week), nonintensive caregivers (1-39 hours per week), intensive caregivers (≥40 hours per week), and those without grandchildren.

MAIN OUTCOMES AND MEASURES: Dementia was assessed using both self-reports and proxy measures, with dementia defined by scores of 0 to 6 on the modified Telephone Interview for Cognitive Status or a score of 4 or higher on the Informant Questionnaire on Cognitive Decline in the Elderly.

RESULTS: From an initial cohort of 18 605 participants, 10 058 were included (5062 men [50.3%]; 4996 women [49.7%]; mean [SD] age, 60.9 [7.2] years). Nonintensive grandchild caregiving was associated with lower odds of dementia (odds ratio [OR], 0.76; 95% CI, 0.60-0.97) than no grandchild care. The mediation analysis revealed that the association of nonintensive grandchild care with dementia odds was partially mediated by mobile telephone ownership (17.68%; 95% CI, 2.05%-37.23%), broadband internet access (17.36%; 95% CI, 5.37%-30.05%), and reduced loneliness (16.83%; 95% CI, 4.52%-30.24%), with a combined mediating proportion of 36.99% (95% CI, 25.01%-51.41%). Neither intensive grandchild caregiving nor having no grandchildren was associated with dementia odds, and no significant indirect effects were observed through the mediators examined.

CONCLUSIONS AND RELEVANCE: In this cohort study of older Chinese adults, nonintensive grandchild caregiving was associated with lower odds of dementia, partly owing to increased digital technology access and reduced loneliness. Promoting digital inclusion and social engagement could be beneficial for cognitive health, particularly among older adults providing moderate levels of grandchild care.

PMID:40632534 | DOI:10.1001/jamanetworkopen.2025.19622

JAMA Netw Open. 2025 Jul 1;8(7):e2519630. doi: 10.1001/jamanetworkopen.2025.19630.

ABSTRACT

IMPORTANCE: An association between interstitial lung disease (ILD) and lung cancer has been hypothesized but never established. To date, whether this potential association persists after controlling for genetic factors has not been addressed.

OBJECTIVE: To evaluate the association between ILD and the subsequent risk of different histological subtypes of lung cancer in the general population and a sibling-controlled cohort.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study incorporated both population-based and sibling-controlled designs and used data from the Swedish Total Population Register and Swedish Multi-generation Register. Participants included individuals born between 1932 and 1987, with follow-up starting January 1, 1987, and continuing until December 31, 2016. Data were analyzed from February 15, 2024, to January 30, 2025.

EXPOSURES: ILD.

MAIN OUTCOMES AND MEASURES: The association between ILD and lung cancer was evaluated using multivariable hazard ratios (HRs) and 95% CIs.

RESULTS: Among the 5 425 976 individuals involved in this study (14 624 with ILD and 5 411 352 from the general population), 2 779 108 (51.2%) were male and most (2 068 062 [38.1%]) were 20 to 40 years of age. Among patients with ILD, most (9630 [65.9%]) were older than 40 years. During a 30-year follow-up period, 40 592 cases of lung cancer were diagnosed among those without ILD (incidence rate, 26.2 per 100 000 person-years) and 227 cases among those with ILD (incidence rate, 355.4 per 100 000 person-years). After adjusting for sex, age, calendar period, educational attainment, and smoking-related diseases, individuals with ILD had a higher risk of lung cancer (HR, 2.16; 95% CI, 1.89-2.46). Sibling-controlled analyses showed a higher risk (HR, 2.91; 95% CI, 1.98-4.27). Elevated risks were observed for adenocarcinoma (HR, 1.60; 95% CI, 1.28-2.01), squamous cell carcinoma (HR, 2.56; 95% CI, 1.99-3.29), small cell carcinoma (HR, 3.29; 95% CI, 2.32-4.68), and other histological types (HR, 2.32; 95% CI, 1.78-3.01). Results from sibling-controlled analyses generally mirrored these findings.

CONCLUSIONS AND RELEVANCE: This large prospective cohort study found that ILD was associated with increased risk of most histological subtypes of lung cancer. Therefore, the presence of ILD should be included in lung cancer risk assessment models.

PMID:40632533 | DOI:10.1001/jamanetworkopen.2025.19630

JAMA Netw Open. 2025 Jul 1;8(7):e2519706. doi: 10.1001/jamanetworkopen.2025.19706.

ABSTRACT

IMPORTANCE: Childhood bereavement increases the risk of common psychiatric disorders later in life. However, the role of stress resilience in this association remains underexplored.

OBJECTIVE: To assess whether stress resilience mediates the association between childhood bereavement and psychiatric disorder risk in adulthood.

DESIGN, SETTING, AND PARTICIPANTS: Three matched cohort studies were performed using data recorded in the Swedish Military Conscription Register. Individuals with childhood loss of either a parent or a sibling (19 162 participants), a parent (16 247 participants), or a sibling (3023 participants) due to death from 1987 to 2020, together with 10 unexposed individuals per exposed individual, were matched on sex, birth year, and county of birth. All participants had available stress resilience measure at conscription. Data were analyzed from February to December 2024.

EXPOSURES: Childhood bereavement was ascertained from the Swedish Multi-Generation and Causes of Death Registers.

MAIN OUTCOMES AND MEASURES: Incident diagnosis of depression, anxiety, substance use disorder, and stress-related disorder was ascertained from the Swedish Patient Register. Cox models were used to estimate the association between childhood bereavement and risk of postconscription psychiatric disorders after multivariable adjustment. Causal mediation analysis was conducted to examine if stress resilience measured at conscription mediated this association.

RESULTS: Among 1 733 085 conscripted individuals (median [IQR] age at conscription 18.2 [18.0-18.5] years; 1 707 960 [98.5%] male), the median (IQR) age of individuals exposed to loss of either a parent or a sibling, parent, or sibling was 13.4 (9.6-15.8), 13.7 (10.4-15.9), and 10.7 (5.5-14.9) years, respectively. The crude incidence rate of any psychiatric disorder was 7.9, 8.1, and 6.6 per 1000 person-years among the 3 groups (5.3, 5.8, and 5.5 per 1000 person-years among the respective unexposed groups). A positive association was noted for loss of either a parent or a sibling (HRs ranged from 1.13; 95% CI, 1.06-1.20 for anxiety to 1.31; 95% CI, 1.23-1.40 for substance abuse disorder) and loss of a parent (HRs ranged from 1.10; 95% CI, 1.01-1.20 for stress-related disorders to 1.19; 95% CI, 1.12-1.27 for depression). For loss of a sibling, the statistically significant associations were for any common psychiatric disorder (HR, 1.12; 95% CI, 1.00-1.25) and stress-related disorders (1.27; 95% CI, 1.04-1.55). Stress resilience partially mediated the associations (proportions for loss of either a parent or a sibling ranged from 10.6%-19.4%, for a parent ranged from 15.6%-21.7%, and for a sibling ranged from 6.2% for stress-related disorders to 18.4% for any common psychiatric disorder).

CONCLUSIONS AND RELEVANCE: In this cohort study of a nationwide Swedish sample, altered stress resilience was found to be one mechanism through which childhood bereavement is associated with risk of psychiatric disorders later in life.

PMID:40632532 | DOI:10.1001/jamanetworkopen.2025.19706

JAMA Dermatol. 2025 Jul 9. doi: 10.1001/jamadermatol.2025.2004. Online ahead of print.

ABSTRACT

IMPORTANCE: No prospective epidemiologic studies have investigated genetic vs environmental factors on the risks of nevus-associated melanoma (NAM) and de novo melanoma.

OBJECTIVE: To determine whether the risk factor profile differs for nevus-associated and de novo invasive melanoma, and whether the associations differ according to sex.

DESIGN, SETTING, AND PARTICIPANTS: This population-based prospective cohort study (the QSkin Study) conducted in Queensland, Australia, included participants aged 40 to 69 years at baseline. Participants were recruited in 2011 and followed up until December 2022. All analyses were conducted between October 2024 and January 2025.

EXPOSURES: Self-reported information from the baseline survey on phenotypic factors (hair color, tanning ability, nevus density, family history), sun exposure-related factors (sunburns, history of skin cancers and actinic lesions), and polygenic risk scores for melanoma and nevus development was collected.

MAIN OUTCOME AND MEASURES: The primary outcome was incident invasive melanoma (nevus-associated and de novo).

RESULTS: A total of 17 752 males and 21 049 females were included and 859 were analyzed. During a median (IQR) follow-up of 11.4 (11.2-11.7) years, 209 participants developed an invasive nevus-associated melanoma (129 in males and 80 in females) and 650 developed an invasive de novo melanoma (362 in males and 288 in females). Many of the known phenotypic and sun exposure-related risk factors for melanoma were similarly associated with nevus-associated and de novo melanoma, but high nevus density and high genetic propensity for melanoma development had significantly higher hazard ratios (HRs) for NAM than de novo melanoma (HR for many moles vs no moles, 6.86 [95% CI, 3.82-12.33] vs 3.21 [95% CI, 2.23-4.63]; P = .001; HR for melanoma polygenic risk score tertile 3 vs tertile 1, 6.46 [95% CI, 3.42-12.20) vs 2.98 [95% CI, 2.21-4.02]; P = .006). No significant differences in the risk factor profile for NAM were found for sex, but the HR for older age was significantly higher among males with de novo melanoma than in females. The site distribution of NAM differed for males and females, occurring mostly commonly on the trunk in males and on the limbs in females.

CONCLUSIONS AND RELEVANCE: Results of this study identified distinct risk factor profiles for NAM and de novo melanomas, particularly polygenic risk and nevus propensity. Males and females tended to develop NAM on different body sites, which may have implications for early detection strategies.

PMID:40632528 | DOI:10.1001/jamadermatol.2025.2004

Epilepsia. 2025 Jul 9. doi: 10.1111/epi.18539. Online ahead of print.

ABSTRACT

OBJECTIVE: The CSMD genes, including CSMD1, CSMD2, and CSMD3, encoding synaptic transmembrane proteins, play important roles in neuronal maturation, growth of dendrites, and processes of synapses. Our recent study showed that CSMD1 was associated with developmental epileptic encephalopathy (DEE) and generalized epilepsy. The significance of CSMD2 and CSMD3 in human disease is unknown.

METHODS: Trio-based whole-exome sequencing was performed in patients with focal epilepsy without acquired etiologies. The gene-disease association was validated by excess and damaging effect of variants, genotype-phenotype correlation, and studies on spatial-temporal and single-cell expression.

RESULTS: CSMD2 variants were identified in six and CSMD3 variants were identified in four cases with focal epilepsy. Additional CSMD3 variants were identified in three cases with febrile seizures plus and one case with infantile spasms. The variants included 1 de novo, 1 homozygous, and 12 pairs of compound heterozygous variants. All variants were missense except one and presented no or extremely low minor allele frequencies, which were significantly lower than that of benign variants and higher in excess by multiple statistical analyses. The gene-disease association was further supported by correlation between damage scoring of variants and phenotype severity. The three CSMD genes are expressed predominantly at early development stages, correlated with the neurodevelopment abnormalities/DEE. CSMD1 expression increases significantly starting with later childhood, consistent with the poor prognosis of DEE. CSMD2 presented the highest expression in the developing brain, with predominance in inhibitory neurons, explaining the focal epilepsy and focal cortical dysplasia (FCD). CSMD3 expressed in relatively low levels with less neuron-specificity explained the heterogeneous phenotypes.

SIGNIFICANCE: The CSMD genes are associated with epilepsies, CSMD2 with focal epilepsy/FCD, and CSMD3 with a phenotype spectrum that includes focal epilepsy, febrile seizures, and DEE. The distinct phenotypes of CSMD genes are explained by their features of genetic dependent stage and the development-dependent expression pattern of neuron specificity.

PMID:40632521 | DOI:10.1111/epi.18539

J Chromatogr Sci. 2025 Jun 10;63(6):bmaf042. doi: 10.1093/chromsci/bmaf042.

ABSTRACT

Terminalia arjuna is a widely recognized medicinal tree known for its diverse pharmacological properties, particularly its cardioprotective effects. This study aimed to quantify two key bioactive triterpenoids, arjungenin and arjunic acid, in T. arjuna bark samples collected from 16 different geographical locations. A validated High-Performance Liquid Chromatography method was developed, demonstrating high precision, accuracy and sensitivity for the simultaneous quantification of these compounds. Statistical analyses, including Hierarchical Cluster Analysis, Principal Component Analysis and heat map visualization, were employed to classify populations based on their phytochemical composition. The results revealed significant variations in arjungenin and arjunic acid content among different populations, with the highest concentrations observed in samples from Amangarh tiger reserve (Bijnor) and Gorakhpur Forest division (Pharenda). These findings were further confirmed by ANOVA and Tukey’s post hoc test. Additionally, variations in yield and total tannin content were observed, suggesting that environmental factors play a crucial role in secondary metabolite biosynthesis. The identification of high-yielding populations highlights the potential for targeted conservation efforts and the selection of superior genetic resources for pharmaceutical and nutraceutical applications. This study provides a comprehensive phytochemical assessment of T. arjuna populations and establishes a reliable analytical method for quality control and standardization. The findings contribute valuable insights into the influence of environmental factors on metabolite production, paving the way for future research on genetic and biochemical pathways regulating triterpenoid biosynthesis in T. arjuna. Moreover, flash chromatography was employed to isolate arjunic acid, and its structure was further validated using 1H-NMR and 13C-NMR spectroscopy, reinforcing the analytical accuracy of the method.

PMID:40632495 | DOI:10.1093/chromsci/bmaf042

J Community Psychol. 2025 Jul;53(5):e70029. doi: 10.1002/jcop.70029.

ABSTRACT

Community sports teams are low-threshold arenas for involvement in physical activities with the potential to promote recovery among persons with experiences of mental health or substance use problems. This study focuses on a community sports team, Psykiatrialliansen (PA), based in Bergen, Norway, to explore how participation may relate to sense of engagement in everyday activities, social inclusion, and life satisfaction. A cross-sectional study was conducted among a sample of members of PA (N = 57), with questions related to participation in activities, as well as measures of sense of engagement, social inclusion, and life satisfaction. In addition to descriptive statistics, the associations between sense of engagement, social inclusion, and life satisfaction were explored. Study participants reported being involved in a range of physical activities. Common self-reported benefits related to mental health, physical health, friendships, and leisure. Sense of engagement, social inclusion, and life satisfaction were significantly positively associated. The results indicate that participation in community sports may be linked with connectedness, belonging, and well-being.

PMID:40632491 | DOI:10.1002/jcop.70029

Drugs Aging. 2025 Jul 9. doi: 10.1007/s40266-025-01229-x. Online ahead of print.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is common in older adults, and anticoagulation is recommended for those aged 75 years and older. Still, many individuals remain untreated due to concerns about the benefit-risk balance, particularly among the frail. This study examines the association of incident ischemic stroke (IS) and major or clinically relevant nonmajor bleeding (MB/CRNMB) on 1-year mortality in older patients receiving oral anticoagulants (OAC).

METHODS: This retrospective multicenter study included individuals aged ≥ 75 years with AF, discharged between 2014 and 2018 from three acute geriatric units. Baseline functional and frailty status were collected. OAC use at discharge was identified through review of clinical charts. Data on 1-year survival, IS, and MB/CRNMB were extracted from a centralized database. Associations with 1-year mortality were analyzed using a multivariable Cox model with IS and MB/CRNMB as time-dependent variables.

RESULTS: The study included 1684 patients with AF, median age 86 years (interquartile range 82-90), of whom 59.8% were female. Most patients were frail (67.2%) or prefrail (24.2%). Within 1 year, 609 (36.2%) patients died; there were 50 (2.9%) cases of IS and 79 (4.7%) cases of MB/CRNMB. Multivariable Cox analysis showed that incident MB/CRNMB (hazard ratio, HR: 3.82, 95% confidence intervals, CI 2.68-5.45) and IS (HR: 1.82, 95% CI 1.14-2.90) were independently associated with increased 1-year mortality.

CONCLUSIONS: In total, one third of older adults with AF receiving OAC die within a year of discharge. Incident MB/CRNMB was more strongly associated with reduced survival than incident IS, underscoring the clinical complexity of anticoagulation management in this high-risk population.

PMID:40632489 | DOI:10.1007/s40266-025-01229-x

Drug Saf. 2025 Jul 9. doi: 10.1007/s40264-025-01576-z. Online ahead of print.

ABSTRACT

BACKGROUND: Affective disorders, particularly depression, are common among women of childbearing age, and pregnancy often exacerbates symptoms. Antidepressants are often required for treatment, but adherence during pregnancy is variable. Although some studies suggest potential risks to the foetus, many cannot rule out confounding by indication. In this context, understanding real-world patterns of antidepressant prescription and adherence during pregnancy is essential to inform clinical practice and ensure adequate mental healthcare.

OBJECTIVE: The aim of the present study was to characterise the use of antidepressants in a cohort of pregnant women using electronic health records.

METHODS: This observational cohort drug-utilisation study assessed antidepressant prescription patterns, adherence and persistence among pregnant women using data from the SIDIAP (Information System for the Development of Research in Primary Care) database in Catalonia from January 2011 to June 2020.

RESULTS: Among 99,605 pregnancies, 14.9% involved antidepressant prescriptions, but only 5.8% of these were collected from pharmacies. The median pregnancy duration was 38.4 weeks, and the median maternal age was 33.5 years. Anxiety was the most common health issue associated with an antidepressant prescription. Paroxetine was the most frequently prescribed antidepressant, although sertraline usage increased over time. Antidepressant prescriptions and adherence decreased during pregnancy, with an increase in the postpartum period. About 11.6% of pregnancies involved a concurrent prescription of another antidepressant, and 29.2% of women resumed antidepressant use after pregnancy. Women who initiated antidepressants during pregnancy were more likely to persist with treatment than those with pre-existing prescriptions.

CONCLUSIONS: Our study describes antidepressant use during pregnancy in Catalonia. It is remarkable that there is a notable gap between antidepressant prescriptions and dispensations. Given the risks of untreated maternal depression, strengthening primary care with adequate resources and personalised support is essential for improving perinatal mental healthcare.

PMID:40632487 | DOI:10.1007/s40264-025-01576-z

Adv Ther. 2025 Jul 9. doi: 10.1007/s12325-025-03286-5. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to describe treatment patterns, frequency of comorbidities, and healthcare cost burden among patients with atopic dermatitis (AD) initiating systemic therapy (or re-initiating it after more than 12 months) versus matched controls without AD.

METHODS: Patients with AD initiating oral corticosteroids (OCS), immunosuppressants (SIS), or biologics between 1/1/2017 and 6/30/2022 (index = first treatment) were identified for analysis in the MarketScan claims databases. Patients were continuously enrolled 12 months before (baseline) and after index (follow-up). Direct and propensity score matching were used to adjust for baseline differences between cases and controls. Comorbidities and all-cause healthcare costs within service categories were compared between AD cases and matched controls during follow-up and treatment patterns were described for all patients with AD.

RESULTS: A total of 20,503 patients with AD were identified. On index,12% initiated biologics, 86% OCS, and 2% SIS, and discontinuation rates were high during follow-up (SIS: 80%; biologics: 35%) The incidence of several comorbidities, including cardiovascular disease, atopic conditions, and mental health disorders, was higher in the AD cohort compared with matched controls (p < 0.001). Patients with AD (vs. matched controls) also had significantly higher mean total all-cause healthcare costs (US$15,134 vs. $6832; p < 0.001).

CONCLUSIONS: Patients with AD who are initiating systemic treatment experience an increased risk of being newly diagnosed with several comorbidities and higher healthcare costs compared with matched controls, which places increased burden on patients and healthcare systems.

PMID:40632479 | DOI:10.1007/s12325-025-03286-5