Tag: nevin manimala

JAMA Netw Open. 2026 Jul 1;9(7):e2626634. doi: 10.1001/jamanetworkopen.2026.26634.

ABSTRACT

IMPORTANCE: Previous research has shown neighborhood environmental interventions can improve health and safety for residents. It is unknown whether these interventions impact opioid overdose outcomes.

OBJECTIVE: To evaluate the association of neighborhood environmental interventions with opioid overdose rates.

DESIGN, SETTING, AND PARTICIPANTS: This quasi-experimental nonrandomized trial used a continuous treatment difference-in-differences design and was conducted in a single neighborhood of Philadelphia, Pennsylvania, between January 1, 2019, and December 31, 2021. The quasi-experimental design used nonrandomized comparator groups to evaluate the associations of neighborhood environmental interventions with opioid overdose rates since randomization was not possible. Data analysis took place between May 2022 and February 2025.

INTERVENTIONS: Community trash pickups, vacant lot cleanups, and abandoned house remediation.

MAIN OUTCOMES AND MEASURES: Outcomes of interest were nonfatal and fatal opioid overdoses.

RESULTS: Of 1667 individual blocks (median household income, $37 821) included in the study geography, 622 blocks (37.3%) received at least 1 intervention during the study period. Among 59 590 residents in the study area, there were 1179 Asian residents (2.0%), 9951 Black residents (16.7%), 23 261 White residents (39.0%), 5016 residents (8.4%) who identified as 2 or more races, and 19 903 residents (33.4%) who identified as another race; 30 286 residents (50.8%) were Hispanic or Latinx. A total of 763 community trash pickups, 483 abandoned house remediations, and 855 vacant lot cleanups were included in analysis. In aggregate, the interventions were associated with a significant reduction in fatal opioid overdoses (change, -6.6%; 95% CI, -10.5% to -2.4%), with no measurable association for nonfatal opioid overdoses (change, -0.0%; 95% CI, -3.4% to 3.5%). Abandoned house remediation was associated with a significant reduction in both fatal (change, -17.6%; 95% CI, -26.2% to -7.9%) and nonfatal (change, -11.5%; 95% CI, -19.0% to -3.3%) opioid overdoses. Community trash pickup was not associated with rates of fatal or nonfatal overdoses. Vacant lot cleanup was not associated with rates of fatal overdoses but was associated with a significant increase in nonfatal overdoses (change, 11.7%; 95% CI, 4.0% to 20.0%). No significant displacement associations were found in other locations.

CONCLUSIONS AND RELEVANCE: In this study of the association of neighborhood environmental interventions with opioid overdose rates, interventions analyzed in aggregate were associated with reduced fatal opioid overdoses outcomes, with no association with nonfatal outcomes. Abandoned house remediation was significantly associated with reduced fatal and nonfatal opioid overdose rates and should be considered along with other essential interventions that provide treatment and harm reduction to individuals with substance use disorder.

PMID:42536369 | DOI:10.1001/jamanetworkopen.2026.26634

Biometrics. 2026 Jul 1;82(3):ujag122. doi: 10.1093/biomtc/ujag122.

ABSTRACT

In clinical trials, a treatment rarely benefits every patient, underscoring the need to identify subgroups that are more likely to respond. Traditional subgroup analysis approaches, including finite mixture and threshold models, often rely on stringent distributional assumptions and prespecified subgroup structures that may be unrealistic in practice. Moreover, the resulting subgroups can be difficult to interpret and may not generalize well to new patients. To address these challenges, we propose a new least-squares regression framework that accommodates flexible subgroup structure in heterogeneous data. Our model is distribution-free and allows subgroup membership to depend on covariates, while permitting both the number and the organization of coefficient groups to vary across covariates. Building on regularization, we develop a computationally efficient procedure to detect subgroup structure in linear regression coefficients and then use a support vector machine to recover the corresponding partitions, enabling subgroup membership prediction for future individuals. Relative to pairwise fused regularization, our approach substantially reduces computational complexity. We also establish theoretical guarantees for estimation of group-specific parameters and recovery of the underlying partitions. Simulation studies and a real-data application illustrate the practical effectiveness of the proposed method.

PMID:42536360 | DOI:10.1093/biomtc/ujag122

Cancer Epidemiol Biomarkers Prev. 2026 Jul 31. doi: 10.1158/1055-9965.EPI-26-0300. Online ahead of print.

ABSTRACT

BACKGROUND: It is believed that contact of the urothelial lining to carcinogens induces mutations that lead to cancer. Nocturia, waking up at night to urinate, may void carcinogens and reduce risk of bladder cancer.

METHODS: The Cancer Prevention Study-II Nutrition Cohort is a prospective study of cancer incidence that enrolled participants in 1992 with biennial follow-up beginning in 1997. Cases were ascertained through state cancer registry, medical record verification, or death certificate. Cox models were used to calculate hazard ratios(HR) and 95% confidence intervals(95%CI) for the association between nocturia and primary incident bladder cancer.

RESULTS: Among 49,767 males, 2,655 reported being current smokers in 1997 (30,559 former smokers). There were 1,207 bladder cancers over 210-million person-years of follow-up. Adjusting for demographic and health factors, nocturia once/night was associated with 46% decreased risk of bladder cancer among smokers(HR once/night 0.54, 95%CI 0.30, 0.95; HR 2+/night 0.90, 95%CI 0.52, 1.57). We observed no association among non-smokers(HR once/night 1.10, 95%CI 0.72, 1.69; HR 2+/night 1.17, 95%CI 0.75, 1.81) or former smokers(HR once/night 1.17, 95%CI 0.92, 1.49; HR 2+/night 1.12, 95%CI 0.87, 1.43). Our main findings were no longer statistically significant in 2-year(HR 0.58, 95%CI 0.31, 1.09) and 5-year lag models(HR 0.80, 95%CI 0.32, 1.99).

CONCLUSIONS: Only nocturia once per night was associated with lower risk of bladder cancer in current smokers; however, associations were attenuated in lag analyses, and no dose-response was observed.

IMPACT: Nocturia may reduce risk of bladder cancer among smokers. Further work is needed to confirm findings and understand mechanisms.

PMID:42536351 | DOI:10.1158/1055-9965.EPI-26-0300

Drugs Aging. 2026 Jul 31. doi: 10.1007/s40266-026-01324-7. Online ahead of print.

ABSTRACT

BACKGROUND: Loneliness is associated with high-risk medication use in older adults in cross-sectional studies, but the direction of this relationship is unclear.

OBJECTIVE: The aim of this study was to examine the association between loneliness and initiation of potentially inappropriate pain and psychotropic medications, and test for sex interactions.

METHODS: We conducted a retrospective cohort study of community-dwelling respondents to the Canadian Community Health Survey-Healthy Aging who were interviewed between December 1, 2008, and November 30, 2009, aged ≥66 years, and Ontario residents. Self-reported loneliness was defined at baseline as a score of ≥6 on the Three-Item Loneliness Scale. Survey responses were linked to health records; respondents were followed for 3 years to assess initiation of a potentially inappropriate pain or psychotropic medication, defined using the 2019 American Geriatrics Society’s Beers Criteria. We used weighted Cox proportional hazards regression models to estimate adjusted hazard ratios (HRs) and tested for sex interactions.

RESULTS: Of 2348 respondents (female 54.6%, mean age 75.4 years), 383 (12.3%) were lonely. Compared with those who were not lonely, lonely female respondents had higher rates of initiating potentially inappropriate pain medications (HR at 90 days: 1.57, 95% CI 0.96-2.27; 630 days: 1.52, 95% CI 1.05-2.12; 1080 days: 3.22, 95% CI 1.22-7.78) and potentially inappropriate psychotropic medications, but the latter estimates were imprecise. No association was found in males.

CONCLUSION: Lonely older females initiate potentially inappropriate pain and psychotropic medications at higher rates than those who are not lonely. Screening for loneliness could prioritize patients for medication reviews, possible deprescribing, and interventions that address root causes.

PMID:42536335 | DOI:10.1007/s40266-026-01324-7

Folia Microbiol (Praha). 2026 Jul 31. doi: 10.1007/s12223-026-01567-2. Online ahead of print.

ABSTRACT

Antibiotic resistance is the ability of microorganisms to survive and proliferate despite exposure to antibiotics that would normally inhibit or kill susceptible strains. This resistance can make antibiotics ineffective or diminish their ability to combat microorganisms, complicating the treatment of infections and potentially leading to serious complications. To combat antibiotic resistance, a comprehensive analysis of changes in the metabolic activities of microorganisms is crucial for understanding the underlying mechanisms. Proteus mirabilis is a critical pathogen, particularly as a common cause of urinary tract infections (UTIs), especially in women. Typically, treating P. mirabilis infections relies on antibiotic-based therapies. However, when faced with resistant strains, treatment options become limited. This research aims to simulate how antibiotic resistance develops in P. mirabilis when exposed to sub-inhibitory concentrations of ampicillin and to explore whether ampicillin-resistant strains display cross-resistance to other antibiotics through metabolomic approaches. For this purpose, P. mirabilis strains were gradually exposed to sub-inhibitory concentrations of ampicillin using the disk diffusion method, leading to the selection of resistant passages. Ampicillin and ceftazidime were then applied to both ampicillin-resistant passages and sensitive control strains, and differences in their metabolomic profiles were compared. The metabolomic data obtained from this study were supported by statistical and bioinformatics analyses to facilitate metabolic pathway mapping, comprehend metabolic alterations, and identify interactions among metabolites. Metabolomic studies in antibiotic resistance research provide valuable insights into identifying metabolic alterations in resistant microorganisms, understanding microbial responses to antibiotic exposure, clarifying the effects of antibiotics on metabolic pathways, and gaining a comprehensive perspective on the mechanisms of antibiotic resistance.

PMID:42536331 | DOI:10.1007/s12223-026-01567-2

Ann Nucl Med. 2026 Jul 31. doi: 10.1007/s12149-026-02255-4. Online ahead of print.

ABSTRACT

Partial volume effects (PVE) in positron emission tomography (PET) imaging introduce quantification inaccuracies, particularly in small or heterogeneous lesions, necessitating precise correction methodologies. This study systematically evaluates the performance of statistical versus machine learning approaches in partial volume correction (PVC) across multiple PET reconstruction algorithms, including TrueX, TrueX + TOF, and Iterative + TOF. Phantom experiments were conducted across a broad range of lesion-to-background contrast ratios and lesion sizes to derive and validate exponential recovery coefficient (RC) fitting models. Additionally, advanced machine learning algorithms, including Random Forest, Support Vector Regression, and Gradient Boosting, were implemented to enhance PVC accuracy. The results demonstrate that Iterative + TOF reconstruction yielded the most consistent RC estimates, while machine learning-based PVC significantly outperformed traditional exponential fitting in minimizing residual errors. Among the machine learning models, Random Forest exhibited the lowest root mean square error (RMSE) and highest coefficient of determination (R²), indicating superior predictive accuracy and robustness. These findings underscore the potential of machine learning-driven PVC methodologies for standardizing PET quantification, thereby improving lesion characterization, therapy response assessment, and multi-center data harmonization.

PMID:42536328 | DOI:10.1007/s12149-026-02255-4

Clin Rheumatol. 2026 Jul 31. doi: 10.1007/s10067-026-08325-2. Online ahead of print.

ABSTRACT

PURPOSE: The clinical benefit of combining leflunomide (LEF) with tumor necrosis factor inhibitors (TNFi) in psoriatic arthritis (PsA) remains uncertain. We aimed to evaluate the efficacy and treatment durability of LEF-TNFi compared with non-LEF regimens (predominantly methotrexate (MTX)-TNFi and TNFi monotherapy).

METHODS: This retrospective cohort included 492 biologic-naive PsA patients initiating TNFi (2003-2020): LEF-TNFi (n = 85) versus non-LEF (n = 407). Multiple imputation addressed missing data, and propensity score matching (7 covariates; caliper 0.2 standard deviations of the logit-propensity score) addressed confounding by indication. Longitudinal outcomes were analyzed using linear mixed-effects models; treatment modification was evaluated via Cox models. Reasons for treatment modification were examined descriptively using a competing risks framework.

RESULTS: Substantial baseline imbalances (23 of 36 variables with standardized mean difference > 0.10) were eliminated by propensity score matching (0 of 7 matching covariates with SMD > 0.10; 96.9% of LEF patients retained). Post-adjustment, longitudinal disease activity trajectories did not differ significantly between groups (time-by-treatment interactions: Disease Activity Score in 28 joints (DAS28), p = 0.862; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), p = 0.308). Overall treatment modification rates were similar (propensity score-matched hazard ratio (HR) = 1.16; 95% confidence interval (CI), 0.53-2.51; p = 0.709). Descriptively, LEF patients were more frequently subject to treatment modification for remission (10.6% vs. 5.9%) and less frequently for inefficacy (5.9% vs. 11.1%), although cause-specific hazard ratios did not reach statistical significance.

CONCLUSION: After propensity score adjustment, LEF-TNFi showed no detectable difference in disease activity trajectories or overall treatment persistence compared with MTX-TNFi and TNFi monotherapy. However, LEF-TNFi modifications were predominantly driven by achieved remission rather than inefficacy. Keypoints • Propensity score-adjusted analyses revealed no detectable difference in disease activity trajectories between the LEF-TNFi, MTX-TNFi, and TNFi monotherapy groups in psoriatic arthritis. • Competing risks analysis showed that LEF modifications were driven by remission rather than inefficacy, a clinical distinction obscured by standard composite endpoints. • These hypothesis-generating findings suggest that LEF may be a viable alternative to MTX as concomitant csDMARD therapy with TNFi in PsA.

PMID:42536327 | DOI:10.1007/s10067-026-08325-2

Clin Rheumatol. 2026 Jul 31. doi: 10.1007/s10067-026-08341-2. Online ahead of print.

ABSTRACT

BACKGROUND: Hashimoto’s thyroiditis (HT) and Sjögren’s syndrome (SS) frequently co-occur clinically, implying a potential association between the two diseases. However, their genetic association remains unclarified. To investigate whether there is a genetic link between HT and SS, we performed a two-sample bidirectional Mendelian randomization (MR) analysis.

METHODS: Data for HT were obtained from the IEU Open GWAS project, consisting of 15,654 cases and 379,986 controls. Data for SS were sourced from FinnGen Release 11, with 2981 cases and 439,424 controls included. We adopted the inverse variance-weighted (IVW) method plus four complementary robust MR methods to evaluate the genetic association between HT and SS. Comprehensive sensitivity analyses were implemented to verify the robustness of the MR estimates. Furthermore, a reverse MR analysis was performed to explore the potential for reverse association.

RESULTS: After rigorous screening, seven single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for HT, while six SNPs served as IVs for SS. Positive MR analysis revealed a statistically significant causal effect of HT on SS, with an IVW odds ratio (OR) of 1.2188 (95% confidence interval (CI): 1.0755-1.3813; P = 0.0019). This finding was further validated by the weighted median and weighted mode methods (P < 0.05). Conversely, inverse MR analysis identified a statistically significant causal effect of SS on HT, with an IVW OR of 1.2154 (95% CI: 1.1387-1.2972; P < 0.001). This result was corroborated by the weighted median, MR-Egger, weighted mode, and simple mode methods (P < 0.05). Sensitivity analysis confirmed the robustness of these findings.

CONCLUSIONS: This study identifies a bidirectional genetic association between genetically predicted HT and SS in European populations. The observed relationship is likely attributable to shared autoimmune predisposition. These results may offer a useful reference for exploring their underlying pathogenesis. Key Points • HT and SS often coexist in clinical practice; nevertheless, the exact genetic relationship between 3 them remains to be elucidated. • A two-sample bidirectional MR approach was employed to evaluate the genetic relationship between HT and SS. • Our MR study identified a bidirectional genetic association between genetically predicted HT and SS in European populations.

PMID:42536326 | DOI:10.1007/s10067-026-08341-2

Endocrine. 2026 Jul 31;91(1):241. doi: 10.1007/s12020-026-04701-9.

ABSTRACT

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, may improve metabolic health before conception. However, their association to hypertensive disorders of pregnancy (HDP) after periconceptional or early pregnancy exposure remains unknown.

METHODS: We performed a meta-analysis to investigating association between GLP-1 RAs preconception or first trimester of gestation exposure and HDP risk. Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov, PubMed, Scopus, and EMBASE databases were searched from inception through December 15, 2025. All eligible studies were observational cohorts. Case reports, reviews, editorials, and studies that lacked HDP data were excluded. We pooled odds ratios with 95% confidence intervals using a random-effects Mantel-Haenszel model. ROBINS-I tool was used to evaluate risk of bias.

RESULTS: Of 75 records identified, 3 retrospective cohort studies met inclusion criteria with 10,880 pregnancies (4942 exposed to GLP-1 RAs and 5938 unexposed). All the studies were conducted in the United States between 2014-2025 and evaluated the semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, lixisenatide, and albiglutide exposure. Two studies showed a lower HDP risks among exposed pregnant, whereas one study found a higher risk. In the pooled analysis, GLP-1 RA exposure showed a HDP risk with an OR 0.91 (OR 0.91, CI 0.57-1.47) with no statistical significance.

CONCLUSION: Periconceptional or first-trimester exposure to GLP-1 RAs are not significantly associated with HDP risk. This available evidence is limited and indicating the need for large prospective studies to establish a possible association between GLP-1 RAs are not significantly associated with HDP risk.

PMID:42536323 | DOI:10.1007/s12020-026-04701-9

Drug Saf. 2026 Jul 31. doi: 10.1007/s40264-026-01697-z. Online ahead of print.

ABSTRACT

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol have been associated with neutropenia and agranulocytosis with inconsistent results.

OBJECTIVE: To investigate the risk of neutropenia in association with frequently used NSAIDs compared to paracetamol.

METHODS: We conducted a cohort study using the UK-based Clinical Practice Research Datalink (CPRD) GOLD. In three pairwise comparisons, we compared the risk of neutropenia including agranulocytosis (defined by Read codes) between new NSAID users (diclofenac, ibuprofen, and naproxen) and new paracetamol users (active comparator) during a maximum follow up of 60 days. Secondary and tertiary outcomes additionally included (1) in-patient diagnosed agranulocytosis and (2) laboratory values indicating neutropenia. Both were additionally restricted to only agranulocytosis. We applied propensity score-fine stratification to control for measured confounding and quantified incidence rates (IRs) as well as hazard ratios (HRs) with 95% confidence intervals (CIs).

RESULTS: Our weighted cohorts included 1,003,314 (paracetamol) to 2,207,612 (diclofenac) patients. Weighted IRs of neutropenia (primary outcome) were between 2.1/10,000 person years (PYs) and 2.3/10,000 PYs. HRs for the primary outcome ranged between 1.00 (95% CI 0.51-1.94) and 1.12 (95% CI 0.57-2.23) for NSAIDs versus paracetamol. The secondary and tertiary outcome yielded reduced HRs between 0.53 and 1.03, and even lower HRs when restricted to agranulocytosis (HR between 0.19 and 0.51).

CONCLUSION: Our results indicate no risk of neutropenia for NSAIDs when compared to paracetamol. An increased risk of agranulocytosis in association with paracetamol is possible, but residual confounding by frailty may at least partially explain this association.

PMID:42536322 | DOI:10.1007/s40264-026-01697-z