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Nevin Manimala Statistics

Metformin and the Development of Age-Related Macular Degeneration

JAMA Ophthalmol. 2025 Sep 18. doi: 10.1001/jamaophthalmol.2025.3070. Online ahead of print.

ABSTRACT

IMPORTANCE: Metformin has demonstrated protective effects in systemic diseases, including cancer, cardiovascular disease, and retinal diseases, such as diabetic retinopathy and choroidal neovascularization. Literature suggests metformin may reduce the risk of age-related macular degeneration (AMD), but a consensus has not been reached.

OBJECTIVE: To evaluate the association of metformin with the development of any AMD and progression to geographic atrophy and neovascular AMD using a large electronic health record (EHR) platform.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study had 2 exposed cohorts of participants aged 65 years or older who were prescribed metformin: one without AMD to assess development of any AMD and the other with mild or moderate nonexudative AMD to evaluate AMD progression to geographic atrophy or neovascular AMD. Corresponding nonexposed cohorts consisted of participants not prescribed metformin. Participants were required to meet inclusion criteria at least 6 months before the outcome of interest occurred. Those who had outcomes of interest before meeting inclusion criteria were excluded from analysis. This cohort study used a federated health research platform aggregating deidentified EHR data from 70 institutions (TriNetX). Data were collected from January 2013 to June 2025 and analyzed from September 2024 to June 2025.

EXPOSURES: Participants prescribed metformin.

MAIN OUTCOMES AND MEASURES: Propensity score matching controlled for confounders, such as age, sex, race, hypertension, diabetes, and other systemic conditions. Risk ratios (RRs) with 95% CIs were calculated to compare outcomes at 5 years, 10 years, and any time after meeting criteria. Any confidence intervals that crossed 0.90 to 1.10 were considered statistically not significant. Comparisons between exposed and unexposed groups were repeated requiring a diagnosis of cataract.

RESULTS: Before propensity score matching, cohort 1 (no AMD) included 297 008 participants exposed to metformin (mean [SD] age, 74.9 [7.0] years; 157 584 [53.1%] female) and 1 269 644 participants unexposed to metformin (mean [SD] age, 76.8 [7.9] years; 738 640 [58.2%] female). Before propensity score matching in cohort 2 (early or intermediate nonexudative AMD), there were 12 843 participants exposed to metformin (mean [SD] age, 79.5 [7.2] years; 7107 [55.3%] female) and 77 279 participants unexposed to metformin (mean [SD] age, 81.6 [7.2] years; 48 491 [62.7%] female). After propensity score matching, participants prescribed metformin had comparable risk of developing any AMD relative to those not prescribed metformin (RR, 0.90; 95% CI, 0.86-0.94). When stratified by time, the risk remained similar at 5 years (RR, 0.94; 95% CI, 0.90-0.99) and 10 years (RR, 0.91; 95% CI, 0.87-0.94). Similarly, participants prescribed vs not prescribed metformin had a comparable risk of AMD progression over these time spans (RR for geographic atrophy, 0.87; 95% CI, 0.76-1.01; RR for neovascular AMD, 1.03; 95% CI, 0.91-1.17).

CONCLUSION AND RELEVANCE: This study suggests that, overall, metformin is not associated with significant development or progression of AMD. Further studies and prospective analyses are necessary to evaluate whether dosage and longevity of metformin use are associated with AMD development or progression.

PMID:40965862 | DOI:10.1001/jamaophthalmol.2025.3070

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Development of a simple diagnostic tool predicting the aseptic nature of a joint effusion: a pragmatic pilot study

Diagnosis (Berl). 2025 Sep 12. doi: 10.1515/dx-2025-0041. Online ahead of print.

ABSTRACT

OBJECTIVES: Among all of the swollen joints undergoing an aspiration in primary care, approximately 92 % are of nonseptic cause. This study therefore sought to develop a predictive model, based on simple clinical and paraclinical data, with the aim of predicting the aseptic nature of joint effusion.

METHODS: This is a cohort, prospective, monocentric study. Some explanatory variables were predetermined on the basis of the literature review. A predictive model has been established based on these variables. In order to prioritise the negative predictive value, a cut-off point considering the best specificity for an observed sensitivity greater than or equal to 98 % was retained.

RESULTS: A total of 328 participants, 49.1 % of whom were women, were included in this study, with a median age of 69 years. The median duration of evolution of joint effusion before the puncture was 30 days. Joint fluid had inflammatory characteristics in 46.0 % of cases and 8 septic arthritis were identified. The area under the receiver operating characteristic (ROC) curve of the predictive model was evaluated at 0.93. The model includes the maximum temperature, the polyarticular nature of the clinical picture and the macroscopic appearance of the joint fluid.

CONCLUSIONS: This study made it possible to develop a simple and easily accessible predictive model in a primary care setting. This tool could make it possible to exclude a priori the septic aetiology of one out of four native joint effusions. Its performances remain to be determined on an independent population in a subsequent study (confirmation cohort in progress).

PMID:40965856 | DOI:10.1515/dx-2025-0041

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Relationships Between Body Composition and Mental Health During Pregnancy Are Moderated by Physical Activity and Diet

J Clin Psychiatry. 2025 Sep 15;86(4):25m15822. doi: 10.4088/JCP.25m15822.

ABSTRACT

Objective: This study examined the relationships between body fat mass percentage and mental health (depression and anxiety symptoms) during pregnancy, while assessing the moderating effects of physical activity and diet quality.

Methods: A prospective cohort of 219 pregnant women was recruited for a longitudinal study of maternal health during pregnancy and offspring outcomes. Pregnant participants were assessed at ∼12 and ∼36 weeks of pregnancy. Body composition was measured using air displacement plethysmography, physical activity was measured with ActiGraph wearables, and diet was measured using the National Institute of Health Diet History Questionnaire-III. Depression and anxiety symptoms were also evaluated using the Beck Depression Inventory-II and State-Trait Anxiety Inventory, respectively, at each study visits. Multivariable mixed linear models adjusted for demographic and socioeconomic factors were used to analyze relationships among these parameters. The study period is from October 2019 to August 2024.

Results: Higher body fat mass percentage was significantly associated with increased depression (β= 0.246, P=.014) and anxiety scores (β= 0.241, P=.002). Physical activity moderated the effect of body fat on depression (interaction β=-0.001, P=.017), while diet quality moderated the effect of body fat on anxiety (interaction β=-0.002, P=.047).

Conclusion: Higher body fat mass during pregnancy is associated with more symptoms of depression and anxiety. However, increased physical activity and adherence to high-quality diets can attenuate these effects, indicating that lifestyle interventions during pregnancy may improve mental health of pregnant women, particularly for those with obesity.

PMID:40965852 | DOI:10.4088/JCP.25m15822

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Efficacy and Safety of Rb-bFGF in Hair Transplantation: A Prospective and Comparative Study

J Cosmet Dermatol. 2025 Sep;24(9):e70464. doi: 10.1111/jocd.70464.

ABSTRACT

OBJECTIVE: This prospective randomized controlled trial aimed to evaluate the clinical value of recombinant bovine basic fibroblast growth factor (rb-bFGF)-based combined therapy in hair transplantation, focusing on its optimization effects on follicle survival rate, postoperative hair-loss dynamics, complication control, and patient satisfaction.

METHODS: Sixty patients with moderate-to-severe androgenetic alopecia were randomly assigned to either an rb-bFGF group or a control group. In the rb-bFGF group, harvested follicles were intraoperatively immersed in an rb-bFGF-enriched solution and patients received postoperative topical rb-bFGF gel for 3 weeks, in addition to baseline medications and minoxidil. Control group follicles were stored in saline, with postoperative minoxidil alone. Quantitative assessments include measurements of hair follicle viability and hair density at 3, 6, and 12 months postoperatively. Patient satisfaction was assessed using a three-level scale, and complication rates were recorded.

RESULTS: The rb-bFGF group demonstrated superior outcomes compared with controls, including higher 12-month follicle survival (91.1% vs. 81.0%), lower hair-loss rate (11.6% vs. 22.7%), greater patient satisfaction (96.7% vs. 80.0%), and fewer complications (20.0% vs. 85.3%). All differences were statistically significant (p < 0.001).

CONCLUSION: Intraoperative follicle immersion and postoperative topical application of rb-bFGF significantly enhance graft survival, reduce early hair loss, decrease complications, and improve overall outcomes in hair transplantation.

PMID:40965846 | DOI:10.1111/jocd.70464

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Ketamine Reduces Suicidality-Associated Emergency Department Utilization in Patients With Treatment-Resistant Depression: A 6-Month Mirror-Image Study

J Clin Psychiatry. 2025 Sep 17;86(4):25m15941. doi: 10.4088/JCP.25m15941.

ABSTRACT

Background: Short-term studies have demonstrated antisuicidal effects of ketamine/esketamine for patients with treatment-resistant depression (TRD). However, long-term data and their impact in reducing suicidality-related health care utilization are limited. This 6-month mirror-image study compares suicidality-associated emergency department (ED) visits before and after acute treatment with ketamine/esketamine in a TRD cohort.

Method: This study included adults with TRD evaluated at Mayo Clinic Depression Center (Rochester, Minnesota) from May 2018 to May 2024, who received an acute series of intravenous (IV) ketamine or intranasal (IN) esketamine treatments. The primary outcome measure was the number of suicidality-associated ED visits in the 6 months before and after treatment. Negative binomial mixed-effects model was utilized to analyze suicidality-associated ED visits per person, estimating incidence rate ratios (IRRs) and 95% confidence intervals for the change between pre-and posttreatment periods.

Results: Of 124 eligible individuals, 27 were excluded due to unavailable data, leaving 97 for analysis. The cohort was 69% female, with a median age of 48.9 years; 97% had major depressive disorder, and most (75%) received IV ketamine. After the acute treatment phase, ED visits for suicidal ideation decreased by 84% (IRR=0.16, 95% CI, 0.06-0.46, P=.001), and total ED visits for suicidality decreased by 63% (IRR=0.37, 95% CI, 0.18-0.77, P=.007).

Conclusions: Ketamine and esketamine reduced long-term ED visits for suicidality in individuals with TRD. Further longer-term follow-up research is encouraged to ascertain if these benefits on suicidality reduction are mood state dependent or reflect an independent mechanism.

PMID:40965838 | DOI:10.4088/JCP.25m15941

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Identifying Factors Linked to a Higher Prevalence of Posttraumatic Stress Disorder Among Younger US Military Veterans

J Clin Psychiatry. 2025 Sep 17;86(4):25m15939. doi: 10.4088/JCP.25m15939.

ABSTRACT

Objectives: Posttraumatic stress disorder is a significant public health concern in the US, with military veterans disproportionately affected. Although younger veterans exhibit a higher prevalence of posttraumatic stress disorder (PTSD) compared to their older counterparts, the mechanisms driving this age-related difference remain unclear. This study examined sociodemographic, trauma-specific, and psychosocial factors that may contribute to the elevated prevalence of PTSD in younger (age <50) vs older (age 50 and older) veterans.

Methods: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of US military veterans (n=4,069).

Results: Younger veterans were 3 times more likely to screen positive for PTSD compared to older veterans (weighted 14.7% vs 4.9%, P<.001). Mediation analysis revealed that 90% of the association between younger age and PTSD was indirectly mediated by psychosocial and trauma-specific factors. Psychosocial difficulties contributed the most to accounting for this association (42.9%), followed by loneliness (23.6%), avoidance coping (9.7%), adverse childhood experiences (9.5%), and combat exposure severity (4.2%). Secondary analyses identified interpersonal relationship challenges, substance use and self-blame coping strategies, and childhood physical abuse as key mediators of this association.

Conclusion: Psychosocial and trauma-specific factors may mediate the link between younger age and higher rates of PTSD among US military veterans. These findings underscore the importance of targeted interventions designed to address psychosocial challenges, strengthen social connections, and promote adaptive coping strategies among younger veterans who are at risk for or currently living with PTSD.

PMID:40965837 | DOI:10.4088/JCP.25m15939

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Vocal Fold Scar Treatment via Controlled Dexamethasone Delivery With a Light-Activatable Implant

Laryngoscope. 2025 Sep 18. doi: 10.1002/lary.70149. Online ahead of print.

ABSTRACT

OBJECTIVE: Intralesional steroid injections for vocal fold (VF) scarring are rapidly cleared, limiting their effectiveness. This study evaluates the efficacy of a light-activatable dexamethasone implant compared to a single steroid injection for VF scar healing.

METHODS: Ten rabbits underwent endoscopic VF injury and were treated with either a dexamethasone injection or a light-activatable implant; injured-only and no-injury VFs served as controls. On days 0 and 21, VF implants were irradiated with a near-infrared pulsed laser for 1 min. Larynges were harvested after 42 days. High-speed video (> 10 kHz) of excised larynges captured VF vibrations for kymographic analysis. Normal force, structural stiffness, and displacement were measured. Data were analyzed with appropriate statistical tests.

RESULTS: Compared to injury-only VFs, implant-treated VFs demonstrated significantly reduced normal force and stiffness (5.28 ± 0.77 mN vs. 2.34 ± 0.66 mN, p < 0.0001; 17.74 ± 2.45 mN/mm vs. 6.80 ± 1.32 mN/mm, p < 0.0001), and increased displacement at 1.96 mN (0.14 ± 0.02 mm vs. 0.29 ± 0.05 mm, p < 0.0001) along the injury zone. Implant-treated VFs exhibited larger amplitude ratios and improved tissue architecture than untreated scars. No differences in quantitative measures were observed between implant-treated and injection-treated groups.

CONCLUSION: A light-activatable dexamethasone implant improved VF biomechanics, vibratory behavior, and histological outcomes in a rabbit injury model comparable to a single steroid injection. This novel approach shows promise for delivering controlled, repeatable therapy to VF scars.

PMID:40964826 | DOI:10.1002/lary.70149

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Do ChatGPT and Gemini’s Recommendations Align With Established Guidelines for Hand and Upper Extremity Surgery?

Hand (N Y). 2025 Sep 18:15589447251371089. doi: 10.1177/15589447251371089. Online ahead of print.

ABSTRACT

BACKGROUND: The use of large language models (LLMs) such as ChatGPT and Gemini in clinical settings has surged, presenting potential benefits in reducing administrative workload and enhancing patient communication. However, concerns about the clinical accuracy of these tools persist. This study evaluated the concordance of ChatGPT and Gemini’s recommendations with American Academy of Orthopedic Surgeons (AAOS) clinical practice guidelines (CPGs) for carpal tunnel syndrome, distal radius fractures, and glenohumeral joint osteoarthritis.

METHODS: ChatGPT (version 4o) and Gemini (version 1.5 Flash) were queried using structured text-based prompts aligned with AAOS CPGs. The LLMs’ outputs were analyzed by blinded reviewers to determine concordance with the guidelines. Concordance rates were compared across models, topics, and guideline strength using descriptive statistics and McNemar’s test. The transparency of responses, including source citation, was also assessed.

RESULTS: A total of 174 recommendations were generated, with an overall concordance rate of 62.1%. When comparing concordance rates between LLMs, there was no statistically significant difference between ChatGPT and Gemini (66.7% vs 57.5%, P = .131). Concordance varied by topic and guideline strength, with ChatGPT performing best for moderately supported guidelines. Both models demonstrated low citation transparency. Gemini provided sources for 39.1% of recommendations, significantly more than ChatGPT’s 3.5% (P < .0001).

CONCLUSIONS: Despite modest concordance rates, both models exhibited significant limitations, including variability across topics and guideline strengths, as well as insufficient citation transparency. These findings highlight the challenges in integrating LLMs into clinical practice and emphasize the need for further refinement and evaluation before adoption in hand surgery.

PMID:40964819 | DOI:10.1177/15589447251371089

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Study on a delayed pest management model with pulse chemical control

J Biol Dyn. 2025 Dec;19(1):2548493. doi: 10.1080/17513758.2025.2548493. Epub 2025 Sep 18.

ABSTRACT

Chemical control is crucial in pest management, but delayed responses to pesticide application can significantly affect its success. This study develops a type of novel mathematical models combining delayed impulse differential equations with pulse pesticide spraying to evaluate these delayed effects. The uniform stability of the pest eradication solution is analysed, and key parameters influencing pest control success are explored. Considering delays in both pest population growth reaching environmental capacity and pesticide response, a double delayed impulse differential equation is formulated. The asymptotic stability and exponential stability of the system are studied, and threshold conditions for pest extinction are identified. The findings help optimize pest control strategies under delayed pesticide responses.

PMID:40964803 | DOI:10.1080/17513758.2025.2548493

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High-Throughput Discovery Illuminates Design Principles and Limits for Long-Lived Charged Species in Organic Electrolytes

J Am Chem Soc. 2025 Sep 18. doi: 10.1021/jacs.5c10140. Online ahead of print.

ABSTRACT

The chemical stability of charged molecules in all-organic redox flow batteries (RFBs) is required for the prolonged operation of these devices. Molecular engineering and electrolyte optimization are used to mitigate parasitic reactions and extend the lifetimes of the charge carriers. However, how much can structural variation extend the lifetime? To probe this query, we designed a high-throughput kinetic study of the radical cation of N-methylphenothiazinium, guided by statistical sampling and learning algorithms. Using Argonne’s autonomous discovery facility, we conducted over 6,000 kinetic experiments with robotic sample preparation, parallel kinetic measurements, and machine learning inputs, testing 188 solvent molecules selected from a space of over 540 candidates from 11 chemical classes. Algorithmic selections guided us to stable solvent candidates, which were further tested in high concentration with and without supporting electrolyte. Our findings reveal the inherent difficulty of exceeding the current state of the art through solvent variation. The desired stability is statistically rare and poorly predictable. Among the many tested, only three solvents significantly outperformed our baseline, acetonitrile─and none by more than a factor of 3─suggesting a general challenge in achieving the necessary techno-economic targets. We suggest that self-discharge through solvent homolysis is the cause of the observed limitations. Several structural motifs contribute to >1,000 h half-life stability including molecular simplicity, symmetry, oxidation complement, and strategic fluorination. Importantly, this workflow establishes effective assays for diagnosing and predicting oxidative stress for highly stable liquid electrolytes in all batteries.

PMID:40964797 | DOI:10.1021/jacs.5c10140