Tag: nevin manimala

Ther Drug Monit. 2025 Sep 26. doi: 10.1097/FTD.0000000000001379. Online ahead of print.

ABSTRACT

BACKGROUND: Selective serotonin reuptake inhibitors, including escitalopram, sertraline, and fluoxetine, are frequently prescribed to treat depression and anxiety and obsessive-compulsive disorders in pediatric populations. These medications are associated with potential cardiac side effects, particularly corrected QT (QTc) interval prolongation. This study is the first to evaluate the association between serum concentrations of escitalopram, sertraline, and fluoxetine and QTc interval duration in children and adolescents.

METHODS: This retrospective naturalistic study included 431 patients treated with escitalopram, sertraline, or fluoxetine at the Department of Child and Adolescent Psychiatry, University Hospital, Würzburg, between 2016 and 2019, for whom therapeutic drug monitoring was performed. Serum concentrations of parent compounds, active metabolites, and active moieties were correlated with QTc intervals calculated using Bazett and Fridericia correction formulae.

RESULTS: A total of 287 patients were included in the study (escitalopram, n = 38; sertraline, n = 119; fluoxetine, n = 130). QTc prolongation (>450 ms) was observed in 5.3% of escitalopram, 4.2% of sertraline, and 5.4% of fluoxetine users. A positive correlation was found between QTc duration and serum concentrations of norfluoxetine, the active metabolite of fluoxetine (Bazett: r = 0.18, P = 0.02; Fridericia: r = 0.13, P = 0.07). No statistical association was identified between QTc interval and serum concentration of escitalopram or sertraline. Severe cardiac adverse events, such as Torsade de Pointes or arrhythmias, were not documented.

CONCLUSIONS: These findings suggest a positive correlation between norfluoxetine serum levels and QTc interval duration in children and adolescents. Monitoring norfluoxetine concentration may support individual dose adjustments to minimize the risk of QTc prolongation. However, confirmation in a larger cohort is required before clinical recommendations can be made.

PMID:41004670 | DOI:10.1097/FTD.0000000000001379

Arch Endocrinol Metab. 2025 Sep 26;69(5):e250063. doi: 10.20945/2359-4292-2025-0063.

ABSTRACT

OBJECTIVE: To investigate the Mitochondrial Open Reading Frame of the 12S rRNA type-c (MOTS-c) peptide levels in individuals with obesity compared to those with a normal body mass index and to examine the association of MOTS-c levels with markers of insulin resistance, endothelial function, and inflammation.

METHODS: In this study 85 individuals were enrolled, including 48 with a body mass index ≥ 30 kg/m2 and 37 with a body mass index between 18.5 and 24.9 kg/m2. Individuals with smoking, pregnancy, type 2 diabetes mellitus and other chronic conditions were excluded. Blood samples were collected after at least 8 hours of fasting to measure serum MOTS-c, insulin, high-sensitivity C-reactive protein, and asymmetric dimethylarginine levels. Statistical analyses included t-tests, Mann-Whitney U tests, Chi-squared tests, correlation analyses, and multiple regression analyses.

RESULTS: We found no significant difference in serum MOTS-c levels between individuals with obesity and those with normal body mass index (14.33 ± 3.76 pg/mL versus 13.67 ± 3.44 pg/mL; p = 0.395). Serum MOTS-c levels showed a significant positive correlation with the HOMA-IR index (p < 0.05) but did not correlate with high-sensitivity C-reactive protein or asymmetric dimethylarginine levels. Multiple regression analysis indicated that age and HOMA-IR were significant predictors of MOTS-c levels, with MOTS-c decreasing with age and increasing with higher insulin resistance.

CONCLUSION: Serum MOTS-c levels were similar in individuals with obesity and those with normal weight. The study highlighted age and insulin resistance as significant determinants of MOTS-c levels.

PMID:41004666 | DOI:10.20945/2359-4292-2025-0063

JAMA Oncol. 2025 Sep 25. doi: 10.1001/jamaoncol.2025.3700. Online ahead of print.

ABSTRACT

IMPORTANCE: Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival (iDFS) benefit over NSAI alone in patients with hormone receptor-positive/ERBB2 (formerly HER2)-negative early breast cancer. Evaluating the efficacy and safety of adjuvant ribociclib beyond the planned 3-year treatment period is critical for understanding the long-term impact on recurrences.

OBJECTIVE: To evaluate efficacy and safety of adjuvant ribociclib in an exploratory 4-year analysis of the NATALEE (New Adjuvant Trial With Ribociclib [LEE011]) randomized clinical trial, with all patients no longer receiving ribociclib treatment.

DESIGN, SETTING, AND PARTICIPANTS: This exploratory analysis of an international, open-label, randomized phase 3 trial analyzed adjuvant treatment for premenopausal and postmenopausal women and men with hormone receptor-positive/ERBB2-negative early breast cancer. Eligible patients had anatomic stage IIA (either N0 with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III disease per the American Joint Committee on Cancer Staging Manual, eighth edition. The data cutoff date was April 29, 2024.

INTERVENTIONS: Patients were randomized 1:1 to receive ribociclib (400 mg once daily, days 1-21 of a 28-day cycle, over 36 months) plus NSAI (letrozole, 2.5 mg, or anastrozole, 1 mg, once daily continuously for 60 months) or NSAI alone. Men and premenopausal women also received goserelin (3.6 mg once every 28 days administered subcutaneously).

MAIN OUTCOMES AND MEASURES: The primary end point was iDFS, and secondary efficacy end points included distant disease-free survival, recurrence-free survival, and overall survival. Survival was evaluated by the Kaplan-Meier method.

RESULTS: Among 5101 patients included in the analysis (median [range] age, 52 [24-90] years; 5081 [99.6%] female), the median follow-up for iDFS was 44.2 months (range, 0-63 months). Ribociclib plus NSAI continued to show iDFS benefit over NSAI alone (hazard ratio, 0.72; 95% CI, 0.61-0.84), with 3-year iDFS rates of 90.8% vs 88.1% (difference, 2.7 percentage points) and 4-year rates of 88.5% vs 83.6% (difference, 4.9 percentage points). The efficacy benefit was consistent across subgroups and secondary end points. Overall survival data remain immature, although a trend in favor of ribociclib plus NSAI over NSAI alone was observed (hazard ratio, 0.83; 95% CI, 0.64-1.07). The incidence of adverse events has remained stable.

CONCLUSIONS AND RELEVANCE: This exploratory analysis of the NATALEE randomized clinical trial, with a median follow-up beyond the 3-year treatment duration, demonstrated consistent iDFS benefit with ribociclib plus NSAI over NSAI alone.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03701334.

PMID:40996773 | DOI:10.1001/jamaoncol.2025.3700

JAMA Netw Open. 2025 Sep 2;8(9):e2533186. doi: 10.1001/jamanetworkopen.2025.33186.

ABSTRACT

IMPORTANCE: The Community Eligibility Provision is a federal universal free school meals policy for schools in low-income areas. Expanding access to school meals, which are children’s most nutritious food source, may be a health-promoting policy.

OBJECTIVE: To assess whether school-level adoption of the Community Eligibility Provision was associated with childhood blood pressure outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a difference-in-differences design for staggered policy adoption, observing low-income public and charter schools in 12 US states longitudinally from 2013 through 2019. The medical records for patients aged 4 to 18 years receiving care from community health organizations in the OCHIN health care network were matched to schools based on address. Data were analyzed from April 1 to July 5, 2024.

EXPOSURE: School participation in the Community Eligibility Provision.

MAIN OUTCOMES AND MEASURES: The primary outcome was the annual school-level proportion of patients with a high blood pressure measurement (at or above the 90th percentile for age, sex, and height), and the secondary outcomes included a hypertensive measurement (at or above the 95th percentile) and mean systolic and diastolic blood pressure percentiles.

RESULTS: The sample included 1052 schools matched to 155 778 distinct patients. The mean (SD) proportions of patients based on race and ethnicity were as follows: 0.04 (0.08) Asian patients, 0.46 (0.33) Hispanic patients, 0.01 (0.03) patients of multiple races, 0.01 (0.02) Native Hawaiian or Other Pacific Islander patients, 0.13 (0.22) non-Hispanic Black patients, 0.25 (0.26) non-Hispanic White patients, and 0.09 (0.09) patients with unknown race and ethnicity. The majority of schools (n = 670 [63.7%]) were located in California or Oregon. School participation in the Community Eligibility Provision was associated with a -2.71 percentage point (95% CI, -5.10 to -0.31 percentage point; P = .03) net reduction in the proportion of patients with a high blood pressure measurement, corresponding to a -10.8% (95% CI, -20.4% to -1.2%) net decrease over 5 years. Participation was also negatively associated with the proportion of patients with a hypertensive measurement and with the mean diastolic blood pressure.

CONCLUSIONS AND RELEVANCE: This cohort study of schools matched to child and adolescent patient medical records from a large network of community health organizations found that school participation in the Community Eligibility Provision was associated with a net reduction in blood pressure outcomes. These findings add to mounting evidence that universal free school meals may be associated with improved child health.

PMID:40996762 | DOI:10.1001/jamanetworkopen.2025.33186

Database (Oxford). 2025 Jan 18;2025:baaf059. doi: 10.1093/database/baaf059.

ABSTRACT

Throughout scientific literature and databases, microbial strains are often distinguished using either non-standardized designations or one of several available culture collection numbers. The fact that different sources use different strain identifiers to describe the same strain significantly impedes the findability, reusability, and integration of published information, and also affects the reproducibility of results. In order to ensure the traceability of microbial strains, the new StrainInfo database presented in this work was developed based on the defunct StrainInfo.net portal to re-establish and further develop this important service for the collection and matching of all existing identifiers of microbial strains. New data is collected, standardized, and integrated from culture collection catalogues, sequence databases as well as the scientific literature. A new interface provides easy access to the identifiers, their interrelations, associated information, as well as links to additional data. To improve and encourage the referencing and linking of microbial strain data, StrainInfo has introduced the Digital Object Identifier as a persistent identifier for strains. Database URL: https://straininfo.dsmz.de/.

PMID:40996712 | DOI:10.1093/database/baaf059

Database (Oxford). 2025 Jan 18;2025:baaf054. doi: 10.1093/database/baaf054.

ABSTRACT

Recent advancements highlight the importance of large-scale causal inference in elucidating disease mechanisms and guiding public health strategies. Mendelian randomization (MR) has become a cornerstone method for identifying causal relationships by leveraging genetic variants as instrumental variables. However, existing tools lack flexibility for multivariable analyses and fail to integrate diverse datasets effectively. To address these challenges, we introduce MRdb, a comprehensive database designed for conducting both univariable and multivariable MR analyses. MRdb encompasses 12 distinct categories of exposure data, including but not limited to 19 126 expression quantitative trait loci genes, 4907 plasma proteins, and 1400 plasma metabolites. Additionally, it integrates 48 507 disease outcomes sourced from FinnGen R10 and the IEU Open GWAS Project. MRdb offers robust data preprocessing features, including handling missing statistics, harmonizing datasets, and selecting instrumental variables to ensure high-quality analyses. Collectively, MRdb bridges the gaps in existing tools by integrating diverse datasets with user-friendly functionalities, empowering researchers to explore complex causal mechanisms.

PMID:40996707 | DOI:10.1093/database/baaf054

Infection. 2025 Sep 25. doi: 10.1007/s15010-025-02645-2. Online ahead of print.

ABSTRACT

Post-tuberculosis lung disease (PTLD) is an increasingly recognized condition that significantly affects survivors’ quality of life, creating disability and incrementing the risk of mortality. PTLD includes a spectrum of structural and functional lung impairments such as obstructive, restrictive, and mixed patterns, bronchiectasis, and pulmonary fibrosis that persist beyond microbiological cure. Global prevalence data highlight a heavy burden of PTLD, especially in high-incidence regions, driven by late diagnosis and suboptimal treatment. Functional and radiological evaluation remains critical for timely diagnosis, with spirometry and imaging revealing lasting abnormalities in a large proportion of TB survivors. Multidisciplinary care is essential and includes bronchodilator therapy, infections/complications management and prevention, pulmonary rehabilitation, and, in selected cases, surgical intervention. Despite increasing recognition, standardized diagnostic and therapeutic pathways for PTLD are still lacking, and data on optimal follow-up, rehabilitation strategies, and preventive measures remain limited. Prospective studies, better stratification tools, and patient education initiatives are urgently needed to reduce PTLD morbidity and mortality. This narrative review synthesizes current evidence on PTLD epidemiology, clinical evaluation and management while offering practical suggestions for clinicians taking care of people with TB and addressing research needs.

PMID:40996670 | DOI:10.1007/s15010-025-02645-2

Adv Ther. 2025 Sep 25. doi: 10.1007/s12325-025-03349-7. Online ahead of print.

ABSTRACT

INTRODUCTION: We compared the real-world effectiveness of initiating beclometasone dipropionate/formoterol fumarate (BDP/FOR) versus fluticasone furoate/vilanterol (FF/VI) in a general practice (GP) asthma cohort in England.

METHODS: Patients newly initiating BDP/FOR or FF/VI between 1 December 2015 and 28 February 2019 (index), were selected from anonymised Clinical Practice Research Datalink data. Baseline was < 12 months pre-index with ≤ 12 months follow-up post-index. Eligible patients were aged ≥ 18 years at index, had diagnosed asthma, ≥ 1 FF/VI or BDP/FOR prescription, medical records eligible for linkage to secondary care data and continuous GP-registration ≥ 12 months pre-index. Patients with chronic obstructive pulmonary disease, ≥ 1 fixed-dose inhaled corticosteroid/long-acting β₂-agonist, single-inhaler triple or biologic therapy at index were excluded. The primary study outcome was asthma exacerbation rate. Secondary outcomes included medication persistence and oral corticosteroid (OCS) use. Propensity scores were generated for each treatment comparison; inverse probability of treatment weighting adjusted for confounding in baseline characteristics between groups, applied to each outcome separately. Analyses considered intercurrent events (ICEs; treatment switching, discontinuation, loss to follow-up, death, rescue medication use).

RESULTS: Weighted group standard mean differences showed adequate balance for most covariates. Patients initiating BDP/FOR (n = 46,809) and FF/VI (n = 3773) had numerically similar exacerbation rates per person per year (PPPY) while-on index treatment [measuring outcome until ICE; BDP/FOR, 0.1479 (n = 31,715); FF/VI, 0.1338 (n = 2547); rate ratio 0.9048, p = 0.2841]. Patients continuing uninterrupted index treatment for 12 months had a lower exacerbation rate PPPY for FF/VI [0.0681 (n = 384)] than BDP/FOR [0.1104 (n = 3342); rate ratio, 0.6162 (p = 0.0293)]. For patients initiating FF/VI versus BDP/FOR, treatment persistence was greater [hazard ratio, 0.76 (p < 0.0001)].

CONCLUSION: Overall, patients initiating FF/VI and BDP/FOR had numerically similar exacerbation rates; of the patients continuing 12 months’ uninterrupted treatment, the FF/VI group had a lower exacerbation rate versus BDP/FOR. Patients initiating FF/VI were less likely to discontinue treatment than those initiating BDP/FOR.

PMID:40996636 | DOI:10.1007/s12325-025-03349-7

Pharmacoeconomics. 2025 Sep 25. doi: 10.1007/s40273-025-01541-9. Online ahead of print.

ABSTRACT

OBJECTIVE: This study examines the generalizability of foreign economic evaluations to the Spanish healthcare system. The research aims to describe the cross-country adaptation methods identified in a scoping review of multinational cost-utility analyses and to examine the probability of concordant funding decisions between Spanish and foreign results, as well as to identify factors influencing generalizability.

METHODS: First, a scoping review of multinational studies reporting cost-utility analyses for at least two countries, including Spain, was conducted using MEDLINE, PubMed, Embase and Web of Science in April 2025. Data related to transferability were extracted and a narrative synthesis was performed. Second, a dataset of case comparisons-each defined as a technology against a comparator in a specific population-was developed from the identified studies. Each foreign comparison was matched to its Spanish equivalent within the same study. Incremental cost-effectiveness ratios (ICERs) were converted to 2024 Spanish Euros and compared against a threshold of €30,000 per quality-adjusted life year (QALY). A multilevel logit model was used, with a binary variable indicating decision concordance between Spanish and foreign ICERs/dominance as the dependent variable. We also analysed the distances in the incremental costs and incremental QALYs between countries using a log-normal bivariate model. Country-specific and other study-related factors were considered as independent variables in both models.

RESULTS: The review included 57 studies. Most were funded by drug manufacturers and conducted in Europe. The majority of authors did not specify their reasons for selecting countries. All but three studies attempted to use local costs, probabilities and/or epidemiological data. Twelve studies incorporated country-specific utilities. A total of 644 comparisons were analysed; 142 were Spanish results and 502 were foreign results with their Spanish equivalents. The cost-effectiveness plane quadrant of the foreign result matched the Spanish result in 84% of cases. Assuming a threshold of €30,000 per QALY, the funding decisions were the same in 93% of cases. The probability of decision concordance was higher when the study was conducted in a Eurozone country or in the United Kingdom. Sensitivity analysis showed the variability of decisions depending on the selected cost-effectiveness threshold. Similar variables were found as relevant factors explaining the distance in the incremental QALYs analysis.

CONCLUSION: Foreign cost-effectiveness results of those studies analysing drugs from Eurozone countries such as France, Germany, Italy, or from the United Kingdom can often be generalizable and provide meaningful insights for decision making in Spain. However, these findings should not be used as a reason to avoid country-specific studies if they are feasible. Further research is needed to determine if these findings apply to other health technologies. Limitations of the study include the lack of a formal assessment of the methodological quality of the selected studies and the potential risks of bias.

PMID:40996621 | DOI:10.1007/s40273-025-01541-9

Inflammopharmacology. 2025 Sep 25. doi: 10.1007/s10787-025-01965-x. Online ahead of print.

ABSTRACT

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint destruction, and systemic complications. Despite the availability of conventional therapies, limitations such as adverse effects and incomplete remission necessitate alternative treatment options. Naringenin, a flavanone found abundantly in citrus fruits, exhibits anti-inflammatory, immunomodulatory, and antioxidant properties, making it a potential therapeutic agent for RA. This systematic review and meta-analysis aimed to evaluate the efficacy of naringenin in preclinical in vivo models of RA by synthesizing available evidence on its therapeutic effects on clinical, biochemical, and histopathological parameters. A comprehensive literature search was conducted in PubChem, Google Scholar, and Science Direct following PRISMA 2020 guidelines. Twelve eligible in vivo studies were identified using established inclusion criteria. Data were extracted for arthritis scores, paw volume, body weight, inflammatory cytokines, oxidative stress markers, histopathological outcomes, and cartilage degradation enzymes. Statistical analyses were performed using RevMan 5.4, and effect sizes were calculated as standardized mean differences (SMD) with 95% confidence intervals (CI) under a random-effects model. Naringenin significantly reduced arthritis severity (SMD = – 3.50), paw volume (SMD = – 1.78), and levels of TNF-α (SMD = – 4.94), IL-6 (SMD = – 2.97), IL-1β (SMD = – 5.55), and IL-17 (SMD = – 1.22), while improving antioxidant defenses (SOD, GSH) and reducing oxidative stress (MDA). It also improved histopathology and body weight, and decreased cartilage-degrading enzymes (MMP-3, MMP-9). Heterogeneity was generally low to moderate across analyses. Subgroup analyses revealed that therapeutic outcomes varied by arthritis model, dosage, and treatment duration. Naringenin demonstrates strong anti-arthritic effects in animal models through modulation of inflammatory cytokines, oxidative stress markers, and joint pathology. These findings support its potential as a candidate for further investigation in clinical settings. However, translational studies and human trials are essential to validate its safety, efficacy, and pharmacokinetics in RA management.

PMID:40996618 | DOI:10.1007/s10787-025-01965-x