Nevin Manimala

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

Appl Health Econ Health Policy. 2025 Jul 9. doi: 10.1007/s40258-025-00987-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Health promotion initiatives are often promoted as being worth the investment given future cash-savings. This paper uses the findings of HomeHealth, a health promotion service for older adults with mild frailty, to examine how economic evaluation relates to local decision making in England.

METHODS: The HomeHealth trial randomised 388 participants aged 65+ years with mild frailty to receive HomeHealth (195 participants) or treatment as usual (193 participants). Health and social care resource use and carer time were self-completed at baseline, 6 months and 12 months. Primary and secondary healthcare resource use and medications were collected from patient files at 12 months post recruitment, covering the past 18 months. Stakeholders including commissioners were consulted on the results of the trial and budget impact.

RESULTS: Participants allocated to HomeHealth had a significant reduction in emergency hospital admissions at 12 months (incident rate ratio (IRR) 0.65; 95% confidence interval (CI) 0.45-0.92) and unpaid carer hours at 6 months (- 16 h (95% CI – 18 to – 14 h) or – £360 (95% CI – 369 to – 351) per patient). Although the intervention is cost saving overall due to fewer emergency admissions, at a cost of £457 per patient commissioners do not have the budget to fund it.

DISCUSSION: This case study illustrates the problem with using standard economic evaluation methods to argue for implementation of health promotion initiatives in publicly financed healthcare systems. Although HomeHealth resulted in reduced emergency admissions and may be cost saving to the system as a whole, it is not locally cash releasing. Health promotion initiatives are unlikely to be funded from local budgets without significant system-wide changes.

PMID:40632475 | DOI:10.1007/s40258-025-00987-4

Ir J Med Sci. 2025 Jul 9. doi: 10.1007/s11845-025-04000-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Intramedullary (IM) femoral nailing in the form of cephalomedullary (CM) nailing is a common treatment of intertrochanteric femoral fractures. Previous literature has demonstrated higher revision rates of left intertrochanteric fractures. Helical blade constructs offer a theoretical advantage over a screw design.

OBJECTIVES: The objective of this study is to examine 3 year revision rates for right vs left CM nails with helical blade head screw. No current studies exist which compare revision rates in left versus right IM nails over this defined time period.

STUDY DESIGN AND METHODS: Patients who sustained intertrochanteric femoral fracture subsequently treated by CM nailing between July 2021 and December 2022 were retrospectively identified from a database of orthopaedic patients. Patients were stratified based on left-sided or right-sided fracture. Criteria for inclusion were anterograde femoral nails, performed for Intertrochanteric hip fractures. Exclusion criteria included revision nails, retrograde nails, diaphyseal and subtrochanteric fractures, reverse oblique fracture patterns and prophylactic nails. The primary outcome was 3 year revision rate. Relevant frequency statistics were generated for each cohort with odds ratios comparing revision rates between the two groups.

RESULTS: n = 104 patients were included in the final sample, comprising n = 48 left and n = 56 right sided intertrochanteric fractures who underwent CM nailing. n = 4 (3.8%) TFNAs underwent subsequent surgical revision. Incidence of revision was higher in patients undergoing left IM nailing Left: 3/48, 0.063, Right: 1/56, 0.018, Odds Ratio: 3.667, 95% Confidence Interval: 0.37 – 36.47, p = 0.268).

CONCLUSION: A greater proportion of patients who sustained a left sided intertrochanteric fracture and were surgically treated with CM nailing underwent revision surgery within 3 years of initial surgery compared to right sided CM nails.

PMID:40632474 | DOI:10.1007/s11845-025-04000-8

J Immigr Minor Health. 2025 Jul 9. doi: 10.1007/s10903-025-01726-6. Online ahead of print.

ABSTRACT

Adolescence and early adulthood are associated with an increase in mental health problems. Migration is also a risk factor for mental disorders. Yet, we know little about the risk of mental disorders among young descendants of immigrants. This study aims to investigate the risk of being diagnosed with a mental disorder between the ages of 16-30 years among those born in Norway with at least one immigrant parent compared to those with Norwegian-born parents. Data were sourced from the Medical Birth Registry of Norway, the Norwegian Patient Register, and Statistics Norway. Cox proportional hazard regressions were used to estimate hazard ratios (HR) of receiving diagnoses of depression, anxiety, bipolar affective disorders, eating disorders, and schizophrenia among those with one or two immigrant parents, in total and by parental region of origin. Individuals with Norwegian-born parents were the reference group. Analyses were adjusted for sex, year of birth, and parental education. Individuals with two immigrant parents had a lower hazard of most mental disorder diagnoses, including anxiety, depression, bipolar affective disorder, and eating disorders, compared to those with Norwegian-born parents, but a higher hazard of a schizophrenia diagnosis. Individuals with one immigrant parent showed a higher hazard of mental disorder diagnoses compared to those with two Norwegian-born parents. These patterns were generally consistent across parental regions of origin. The findings show a lower risk of a diagnosis among those with two immigrant parents. It is unclear whether this is due to better health, different patterns of help-seeking or barriers to care. Higher risk of diagnoses among those with one immigrant parent points towards a need for targeted preventive measures.

PMID:40632466 | DOI:10.1007/s10903-025-01726-6

Clin Drug Investig. 2025 Jul 9. doi: 10.1007/s40261-025-01456-5. Online ahead of print.

ABSTRACT

BACKGROUND: Pembrolizumab shows effectiveness in treating metastatic non-small cell lung cancer (metNSCLC), with a subgroup of patients experiencing long-term survival (LTS) benefits. The existence of a LTS subgroup may influence the cost-effectiveness of pembrolizumab monotherapy compared with platinum-based chemotherapy. This study aims to assess the potential implications of such a subgroup on the cost-effectiveness for patients with non-squamous metNSCLC and PD-L1 ≥ 50% who are ineligible for targeted therapies.

METHODS: This study used a decision analytic model based on Dutch real-world data (2008-2014). Two strategies were simulated: (1) a chemotherapy strategy: patients receive chemotherapy in the first-, second-, and third-line; and (2) a pembrolizumab strategy: patients receive first-line pembrolizumab followed by chemotherapy for those progressing to second- and third-lines. The pembrolizumab strategy is evaluated with and without the assumption that there is a LTS subgroup. The LTS subgroup is assumed to be free from metNSCLC-related progression after treatment. Costs (2022 €), including drug costs, other direct medical costs, family costs, and healthcare costs in life years gained, are considered from first-line treatment to death. Effects are measured in quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) is assessed using an €80,000/QALY threshold. Threshold analyses are performed on the size and mortality rate of the LTS subgroup and on the price of pembrolizumab.

RESULTS: QALYs per patient were 0.65 for chemotherapy, 1.24 for pembrolizumab without LTS, and 3.52 for pembrolizumab with LTS. Average costs per patient were €58,800 for chemotherapy, €154,600 for pembrolizumab without LTS, and €178,600 for pembrolizumab with LTS. Pembrolizumab without LTS was not cost-effective compared with chemotherapy (ICER €167,600/QALY), but pembrolizumab with LTS (30% of simulated population) was cost effective (ICER of €43,100/QALY). Threshold analyses showed that a LTS subgroup size of at least 10% or halving the price of pembrolizumab was needed for pembrolizumab to be cost-effective.

CONCLUSIONS: Pembrolizumab is a cost-effective first-line treatment for patients with metNSCLC and PD-L1 ≥ 50% in the Netherlands when at least 10% of patients are long-term survivors. Without long-term survivors, this treatment is not cost-effective. Therefore, it is crucial to consider long-term survivors in assessing the cost-effectiveness of immunotherapy in metNSCLC.

PMID:40632461 | DOI:10.1007/s40261-025-01456-5