Category: Nevin Manimala

Thyroid. 2025 Sep 22. doi: 10.1177/10507256251382559. Online ahead of print.

ABSTRACT

Background: Graves’ disease is the leading cause of hyperthyroidism in children and adolescents, with recent studies indicating a rising incidence. Epidemiological data on trends and determinants influencing this rise remain limited. This study aims to assess the trends in incidence of pediatric Graves’ disease in the United States and stratify incidence patterns based on patient sex, age, geographic region, urban vs. rural setting, and insurance plan type. Methods: This retrospective cohort study utilized the Merative™ Marketscan® outpatient insurance claims database from 2007 to 2022. Pediatric patients diagnosed with Graves’ disease were identified using International Classification of Diseases (ICD)-9 and ICD-10 codes. Annual incidence rates were analyzed over the study period to detect temporal trends. Incidence rates were further stratified by demographic variables including sex, age, geographic region, community setting (urban vs. rural), and insurance plan. Statistical methods included chi-square, ANOVA, and linear regression models to identify significant trends and differences across subgroups. Results: 3377 total new diagnoses of pediatric Graves’ disease were identified during the 16-year study period. The average annual incidence rate was 3.33 per 100,000 (SD = 0.33), with an annual increase of 0.042 per 100,000 (p = 0.39). Marked differences in average annual incidence rates were observed across sex and age group; female patients exhibited greater average annual incidence rate (5.04 per 100,000) compared with male patients (1.67 per 100,000). Adolescents, patients 13-17 years of age, had the highest average annual incidence rate (5.72 per 100,000) compared with other age groups. On multivariable regression analysis, female patients had a significant increase in annual incidence by 1.69 cases per 100,000 compared with male patients [CI: 0.82-2.56]. Adolescents also saw a significant increase in adjusted annual incidence by 4.92 cases per 100,000 compared with the other age groups [CI: 3.80-6.04]. No significant change in annual incidence rate was observed across insurance plan, geographic region, or rural status. Conclusions: This study quantifies and delineates trends in pediatric Graves’ disease incidence in the United States. The greatest average incidence rate was observed among female and adolescent patients. This study underscores the importance of monitoring Graves’ disease trends to facilitate early disease detection and management. Further research is needed to elucidate the genetic and environmental factors underlying these epidemiological trends.

PMID:40982291 | DOI:10.1177/10507256251382559

JAMA Netw Open. 2025 Sep 2;8(9):e2532650. doi: 10.1001/jamanetworkopen.2025.32650.

ABSTRACT

IMPORTANCE: Major depressive disorder (MDD) is among the most prevalent mental health disorders, causing substantial disability and economic burden. Although several first-line treatments exist with mild adverse effects, up to 50% to 60% of patients do not tolerate or respond to them. Ammoxetine, a novel selective serotonin and norepinephrine reuptake inhibitor, has been found to reduce adverse effects and hepatotoxicity and more potent inhibition of serotonin and norepinephrine transporters, making it more tolerable and effective.

OBJECTIVE: To evaluate the efficacy and safety of ammoxetine in treating adults with MDD.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2 randomized clinical trial was a multicenter, double-masked, placebo-controlled, parallel-group, fixed-dose study of ammoxetine treatment in patients with MDD in China. Patients aged 18 to 65 years from 15 study centers were randomized into daily ammoxetine or placebo groups between March 27, 2023, and June 13, 2024, and followed up for 10 weeks.

INTERVENTIONS: Participants were randomized 1:1:1 to 3 treatment groups: ammoxetine 40 mg/d, ammoxetine 60 mg/d, and placebo.

MAIN OUTCOME AND MEASURES: The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to 8 weeks. Efficacy analyses were performed on both the full-analysis and per-protocol sets using least-squares (LS) mean differences. The safety set analysis was performed using descriptive statistics.

RESULTS: Among 239 enrolled patients (mean [SD] age, 30.4 [10.0] years, 158 female [66.1%]), 80 were randomized to the ammoxetine 60 mg/d group, 80 to the ammoxetine 40 mg/d group, and 79 to the placebo group. In the full-analysis set, both ammoxetine doses led to statistically significant improvements in MADRS total scores at week 8 compared with placebo. The LS mean changes (SE) from baseline were -16.7 (1.3) for ammoxetine 40 mg/d, -16.6 (1.3) for ammoxetine 60 mg/d, and -13.5 (1.3) for placebo. The differences vs placebo were -3.3 (97.3 CI, -6.3 to -0.3) for ammoxetine 40 mg/d and -3.1 (97.3% CI, -6.2 to 0.0) for ammoxetine 60 mg/d. Consistent results were observed in the per-protocol set analysis at week 8 for ammoxetine 40 mg/d (LS mean change, -3.2; 97.3% CI, -6.2 to -0.2) and ammoxetine 60 mg/d (LS mean change, -3.18; 97.3% CI, -6.2 to -0.2), both superior to placebo. Treatment-emergent adverse events were reported in 68 participants (85.0%) receiving ammoxetine 60 mg/d, 63 (78.8%) receiving ammoxetine 40 mg/d, and 48 (60.8%) receiving placebo; most were mild to moderate in severity.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial demonstrated superiority over placebo of ammoxetine treatment at both 40 mg/d and 60 mg/d in patients with MDD. In addition, all doses of ammoxetine were generally well tolerated.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05762458.

PMID:40982284 | DOI:10.1001/jamanetworkopen.2025.32650

JAMA. 2025 Sep 22. doi: 10.1001/jama.2025.15185. Online ahead of print.

ABSTRACT

IMPORTANCE: Levodopa enhances dopaminergic signaling and may stimulate neuroplasticity, which could potentially enhance motor recovery after stroke. Levodopa is used in stroke rehabilitation despite mixed evidence for its effectiveness.

OBJECTIVE: To determine whether levodopa compared with placebo, administered in addition to standardized rehabilitation based on active task-oriented training, is associated with enhanced motor recovery in patients with acute stroke.

DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled randomized clinical trial at 13 stroke units and centers and 11 collaborating rehabilitation centers in Switzerland. Between June 14, 2019 (first patient, first visit), and August 27, 2024 (last patient, last visit), 610 patients with acute ischemic or hemorrhagic stroke with clinically meaningful hemiparesis (ie, a total score of ≥3 points on the following National Institutes of Health Stroke Scale items: motor arm, motor leg, or limb ataxia) were randomized 1:1 to receive levodopa or placebo. Statistical analyses were conducted from November 2024 to August 2025.

INTERVENTION: Patients received levodopa/carbidopa (100 mg/25 mg; n = 307) or placebo (n = 303) 3 times daily for 39 days, alongside standardized rehabilitation therapy based on active task-oriented training.

MAIN OUTCOMES AND MEASURES: The primary outcome was the adjusted mean between-group difference in the Fugl-Meyer Assessment (FMA) total score (range, 0-100 points; fewer points indicate worse motor function; 6-point difference considered patient-relevant) at 3 months.

RESULTS: Among the 610 participants (median [IQR] age, 73 [64-82] years; 252 [41.3%] female; median baseline FMA total score, 34 [14-54]), 28 participants died by 3 months, leaving 582 (95.4%) participants eligible for the primary analysis. At 3 months, the median (IQR) FMA total score was 68 (42-85) points in the levodopa group and 64 (44-83) points in the placebo group. The mean difference in the FMA total score between the levodopa and placebo groups was -0.90 points (95% CI, -3.78 to 1.98; P = .54). There were 126 serious adverse events in the levodopa group and 129 in the placebo group; the most common was infection (levodopa, n = 55; placebo, n = 44).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among patients receiving inpatient rehabilitation for acute stroke, levodopa added to standardized rehabilitation did not significantly improve motor function at 3 months compared with placebo plus standardized rehabilitation. These results do not support the use of levodopa as an adjunct to rehabilitation therapy for enhancing motor recovery after acute stroke.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03735901.

PMID:40982270 | DOI:10.1001/jama.2025.15185

Phys Chem Chem Phys. 2025 Sep 22. doi: 10.1039/d5cp01690h. Online ahead of print.

ABSTRACT

The formation of complex organic molecules (COMs) in the interstellar medium (ISM) is central to astrochemistry and prebiotic chemistry, as these species may act as precursors to biomolecules essential for life. Among COMs, glyceraldehyde (HOCH₂CH(OH)C(O)H, GCA) has attracted attention as a potential building block in early biochemical pathways. Although GCA has not yet been detected in the ISM, the presence of structurally related compounds in various astronomical environments suggests that it may form under interstellar conditions. In this study, we employed the automated reaction discovery tool AutoMeKin to systematically explore the gas-phase chemical reaction networks (CRNs) of C₃H₆O₃ (GCA), C₃H₇O₃ (a hydrogenated analog), and C₂H₅O₂. Reaction pathways were characterized at the ωB97XD/Def2-TZVPP level of theory, and rate coefficients for key processes were computed using the competitive canonical unified statistical (CCUS) model, which accounts for multiple dynamic bottlenecks. Our analysis revealed several barrierless pathways leading to GCA or to GCA and a leaving group. Notably, the reaction between glyoxal (HCOHCO) and the HOCHCH₂OH radical, though neither has yet been detected in the ISM, was found to efficiently produce GCA and a formyl radical, with rate coefficients on the order of 5.4-7.9 × 10^-10 cm³ molecule^-1 s^-1 across the 10-100 K temperature range. However, aside from the aforementioned exception, most GCA formation channels result in highly vibrationally excited intermediates that are more likely to undergo rapid unimolecular decomposition than to be stabilized by radiative emission under typical ISM conditions. These results suggest that while gas-phase GCA formation is chemically feasible, it is likely transient and difficult to detect directly. In contrast, alternative products such as formaldehyde, glycolaldehyde, and (Z)-ethene-1,2-diol dominate many pathways and align better with current astronomical observations. This work provides detailed mechanistic and kinetic insights that enhance astrochemical modeling and advance our understanding of molecular complexity in star-forming environments. Furthermore, it highlights the utility of automated CRN exploration for uncovering viable synthetic routes to prebiotic molecules in space.

PMID:40982266 | DOI:10.1039/d5cp01690h

J Glaucoma. 2025 Sep 22. doi: 10.1097/IJG.0000000000002637. Online ahead of print.

ABSTRACT

PRECIS: This study identifies visual acuity and intraocular pressure at 3- and 5-year follow-ups, along with other variables such as media opacity and nystagmus, as key predictors of long-term outcomes in childhood glaucoma, aiding better management and prognostication.

PURPOSE: This study aims to identify key predictive variables of visual acuity (VA) and intraocular pressure (IOP) outcomes in childhood glaucoma. By understanding these factors, the study seeks to improve prognostication and management strategies for pediatric patients.

METHODS: A retrospective analysis was conducted on pediatric glaucoma patients across multiple centers within the Childhood Glaucoma Research Network (CGRN). The study included patients with at least 5 years of follow-up. Variables such as sex, race, ethnicity, age of onset, laterality, and clinical measures including VA and IOP at various stages (initial visit, 3-year, 5-year, and final visits) were evaluated. Additional factors considered were anisometropia, media opacities, nystagmus, anterior segment dysgenesis (ASD), strabismus, and angle closure.

RESULTS: The study included 396 eyes from 243 patients, with a mean age at presentation of 1.5 months. Several variables showed statistically and clinically significant correlations with final outcomes including IOP and VA at both 3-year and 5-year visits, as well as the presence of media opacities, unilateral glaucoma, nystagmus, and ASD. Based on multivariable prediction model analysis the two statistically significant predictors for visual acuity (n=31) were VA at 5-year visit and presence of angle closure. As for IOP outcomes (n=31), significant predictors included were IOP at 5-year visit and presence of nystagmus.

CONCLUSIONS: This multicenter study highlights that VA and IOP measurements at 3 and 5 years post-diagnosis, along with the presence of specific ocular conditions such as media opacity and nystagmus, are crucial in predicting long-term outcomes in childhood glaucoma.

PMID:40982256 | DOI:10.1097/IJG.0000000000002637

J Alzheimers Dis. 2025 Sep 22:13872877251378759. doi: 10.1177/13872877251378759. Online ahead of print.

ABSTRACT

BackgroundDiabetes has been linked to increased prevalence of dementia, but the link between diabetic retinopathy (DR) and Alzheimer’s disease (AD) remains unclear.ObjectiveThis study aimed to evaluate potential associations between DR and AD-related protein biomarkers in plasma and ocular fluid.MethodsA prospective, cross-sectional study collected human blood, vitreous, aqueous, and tear samples and measured amyloid-β (Aβ₄₀, Aβ₄₂), total-tau (t-tau), phosphorylated-tau (ptau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) by digital immunoassays.ResultsThe study included 79 eyes (79 patients) [41 females (59.4%); mean (SD) age 57.1 (12.2) years] of which DR was present in 44 (55.7%). All six biomarkers were significantly higher in plasma in participants with DR compared to those without DR [Aβ₄₀ p = 0.002, Aβ₄₂ p = 0.002, t-tau = 0.013, ptau181 p = 0.005, GFAP p = 0.010, and NfL p < 0.001]. Within vitreous, DR participants had significantly elevated t-tau (p = 0.002), ptau181 (p = 0.049), and NfL (p = 0.006); and within aqueous, higher NfL (p = < 0.001). Neuropsychological testing scores were lower in participants with DR than those without but did not reach statistical significance (Montreal-Cognitive-Assessment: p = 0.070; Mini-Mental-State-Exam: p = 0.057).ConclusionsThis study showed significant increases of AD associated protein biomarkers in plasma, vitreous, and aqueous in patients with DR. These results support a potential biological link between DR and AD pathology and suggest that DR, which tends to occur in younger individuals, may be a predictive factor for AD.

PMID:40982223 | DOI:10.1177/13872877251378759

J Urban Health. 2025 Sep 22. doi: 10.1007/s11524-025-01013-7. Online ahead of print.

ABSTRACT

While both individual- and neighborhood-level factors play a role in the progression from gestational diabetes mellitus (GDM) to type 2 diabetes mellitus (T2DM), few studies have simultaneously examined these two sets of factors. In this retrospective cohort study of 3567 women with a history of GDM, we used multilevel survival analysis to quantify T2DM risk associated with patient-level and neighborhood-level factors. During a mean follow-up of 2.2 years, 195 women (5.5%) developed T2DM. Statistically significant risk factors of T2DM progression included Black or Asian race, preeclampsia, family history of diabetes, and overweight or obesity. Importantly, residing in neighborhoods with a top tertile social deprivation index was also associated with increased risk (HR = 1.78, 95% CI: 1.01-3.14). In addition, after accounting for other factors, the residual clustering associated with neighborhoods conferred a 19% higher risk. Interventions addressing both individual- and neighborhood-level factors, including socioeconomic disparities, are critical to reducing the risk of T2DM in women with GDM.

PMID:40982206 | DOI:10.1007/s11524-025-01013-7

Obes Surg. 2025 Sep 22. doi: 10.1007/s11695-025-08274-w. Online ahead of print.

ABSTRACT

Metabolic-associated steatotic liver disease (MASLD) and its complications represent a growing global health challenge. Both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have demonstrated long-term benefits for liver health and are currently recommended by international guidelines for patients with MASLD who meet surgical criteria. However, few randomized controlled trials (RCTs) have directly compared the hepatic effects of these commonly performed bariatric procedures in this population. A systematic search of PubMed, EMBASE, and Cochrane CENTRAL was conducted to identify RCTs evaluating RYGB and SG in patients with obesity and MASLD, with a minimum follow-up of 12 months. The primary outcome was the change in hepatic fibrosis, assessed by the number of patients with advanced fibrosis postoperatively. Secondary outcomes included changes in liver enzymes and body mass index (BMI). Meta-analyses were performed using Review Manager 5.4 and RStudio 4.1.2. Three RCTs comprising 322 patients (160 undergoing RYGB, 162 undergoing SG) were included. Both procedures significantly reduced the number of patients with advanced fibrosis: SG (OR = 4.10; 95% CI: 2.18-7.69; p < 0.0001) and RYGB (OR = 12.78; 95% CI: 5.21-31.37; p < 0.00001). While RYGB showed a higher overall odds of fibrosis improvement compared to SG (OR = 1.63; 95% CI: 0.94-2.81), this difference was not statistically significant (p = 0.08). No significant differences were found between groups in liver enzyme reductions. Both RYGB and SG significantly improved hepatic fibrosis in patients with MASLD, with RYGB demonstrating a stronger, albeit non-statistically significant, trend toward fibrosis resolution. Both procedures also reduced liver enzyme levels, reinforcing the role of metabolic surgery in improving liver-related outcomes in this population.

PMID:40982201 | DOI:10.1007/s11695-025-08274-w

Clin Transl Oncol. 2025 Sep 22. doi: 10.1007/s12094-025-04023-8. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer remains a major global health concern due to its heterogeneous nature influenced by genetic, biological, and environmental factors. Serum biomarkers offer promises for improving diagnostic precision and monitoring treatment response.

OBJECTIVE: To evaluate the diagnostic and prognostic significance of serum biomarkers including CA-125, CA-19-9, and CA-15-3 in breast cancer patients and to explore associations with clinical and biochemical parameters.

METHODS: A retrospective, single-center study was conducted in the Hail region, involving 187 breast cancer patients. Data were extracted from electronic health records. Statistical analyses, including ANOVA and regression models, assessed the relationships between serum biomarkers and clinical variables, such as age, cancer stage, obesity, and laboratory parameters. Serum biomarkers CA-125, CA-19-9, and CA-15-3 were quantified using electro-chemi-luminescence immunoassay (ECLIA) assay with Elecsys kits Roche Diagnostics, with detection limits of ~ 1.0 U/ml and inter-assay variability < 7%.

RESULTS: The highest incidence was observed in women aged 46-55 (26.7%) with obesity present in 50% of cases. Advanced stages (2 and 3) comprised 82.6% of diagnoses. CA-125 levels were elevated in middle-aged patients, while CA-19-9 was higher in younger individuals. CA-15-3 showed increased levels in early-stage cancer, suggesting its utility for early detection. Obesity was linked to increased CA-125 and decreased CA-19-9 levels. Laboratory findings revealed hypocalcemia, elevated bilirubin, high GGT, and increased HbA1c, indicating potential risks of bone metastases, hepatic dysfunction, and poor glycemic control.

CONCLUSION: Serum biomarkers demonstrate significant diagnostic and prognostic potential in breast cancer management. Findings support the importance of early detection, obesity management, and integrated monitoring to enhance outcomes and reduce relapse risk.

PMID:40982199 | DOI:10.1007/s12094-025-04023-8

Pharmaceut Med. 2025 Sep 22. doi: 10.1007/s40290-025-00586-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Regulatory agencies and policy makers increasingly recognize real-world evidence (RWE) as a valuable complement to randomized controlled trials (RCTs) in oncology, yet data on how US physicians who treat cancer use and perceive RWE remain limited. The study aimed to assess attitudes toward RWE among US physicians who treat cancer, including their confidence in interpreting it and reliance across clinical decision contexts.

METHODS: A cross-sectional national survey was administered in November 2024 to licensed US physicians who treat cancer, recruited from the American Society of Clinical Oncology (ASCO) member directory, using a random sample stratified by state population. Inclusion criteria were active US medical licensure and current involvement in oncology patient care. The survey instrument included sections on demographics and practice characteristics; RWE familiarity and usage frequency; comparative reliance on RWE versus RCTs in treatment selection, dosing, and outcome prediction (scales ranging from 0 to 10: 0 = complete reliance on RCT data, 10 = complete reliance on RWE); perceived barriers to adoption (4-point scale); and potential facilitators (4-point scale). Categorical data were summarized as counts and percentages, and continuous variables were summarized as means and standard deviations (SD). Chi-squared tests were used to compare categorical variables across groups, paired t tests were used to assess differences in mean reliance scores, and Spearman’s rho was used to evaluate correlations. Statistical significance was set at p < 0.05.

RESULTS: In total, 128 completed surveys were received. Overall, 94% of respondents (n = 120) were at least “somewhat familiar” with RWE, 14% (n = 18) used it “often,” and 3% (n = 4) reported daily use. 49% (n = 63) felt confident interpreting RWE studies, with late-career physicians (> 20 years of experience) less confident than their early and mid-career peers. Reliance on RWE was lower for treatment selection (mean 3.0, SD 1.7) than for dosing (mean 3.7, SD 2.0) or outcome prediction (mean 3.8, SD 2.0) (p < 0.001). Top barriers included reconciling conflicting RWE versus RCT data, data completeness, and bias. Key facilitators included improved analytical standards, guideline integration, and additional training.

CONCLUSIONS: While awareness of RWE is high among US physicians who treat cancer, they apply it selectively on the basis of clinical context, showing notably lower reliance for treatment selection. Addressing concerns about methodological rigor, data quality, and interpretive skills may strengthen RWE’s integration into oncology care.

PMID:40982185 | DOI:10.1007/s40290-025-00586-7