Tag: nevin manimala

JAMA Netw Open. 2025 Jul 1;8(7):e2517834. doi: 10.1001/jamanetworkopen.2025.17834.

ABSTRACT

IMPORTANCE: Systemic antibiotic use for patients with a non-Clostridioides difficile infection (CDI) is a major risk factor for recurrent CDI. Increasing use of oral vancomycin for secondary prophylaxis against recurrent CDI in this context has uncertain efficacy.

OBJECTIVE: To evaluate whether oral vancomycin prophylaxis compared with placebo is effective against recurrent CDI during and 8 weeks after the end of study treatment.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2, placebo-controlled, double-blind randomized clinical trial was conducted in 4 large health systems across the upper Midwest US. Adults who had completed treatment for CDI within the past 180 days and were taking a systemic antibiotic for a non-CDI indication were enrolled between May 21, 2018, and March 30, 2023, and followed up for 8 weeks after the end of study treatment.

INTERVENTION: Participants were randomized 1:1 to 125 mg of oral vancomycin or placebo once daily during antibiotic use for a non-CDI plus 5 days following cessation of those antibiotics.

MAIN OUTCOMES AND MEASURES: The primary outcome was recurrent CDI incidence during treatment and the 8-week follow-up period. The secondary outcome was vancomycin-resistant Enterococcus carriage in stool.

RESULTS: Among 81 randomized participants (median age, 59 years [IQR, 50-67 years]), all were included in the primary as-randomized analysis (39 in the vancomycin group; 42 in the placebo group). Sixty patients (74.1%) completed 8-week follow-up and were included in the secondary as-completed treatment analysis (31 in the vancomycin group; 29 in the placebo group). Recurrent CDI occurred in 17 of 39 participants in the oral vancomycin group (43.6%) and 24 of 42 in the placebo group (57.1%; absolute difference in percentage, -13.5% [95% CI, -35.1% to 8.0%]). Adverse events occurred in 27 of 39 participants in the oral vancomycin group (69.2%) and 27 of 42 in the placebo group (64.3%). Vancomycin-resistant Enterococcus carriage was found in 15 of 30 patients in the oral vancomycin group (50.0%) and 6 of 25 in the placebo group (24.0%) (P = .048) 8 weeks after treatment.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the incidence of recurrent CDI was lower (though did not reach significance) in participants taking oral vancomycin compared with those taking placebo. Because the study was underpowered, it was unable to reveal firm conclusions about the efficacy (or lack thereof) of vancomycin prophylaxis with respect to recurrent CDI.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03462459.

PMID:40601321 | DOI:10.1001/jamanetworkopen.2025.17834

JAMA Netw Open. 2025 Jul 1;8(7):e2518513. doi: 10.1001/jamanetworkopen.2025.18513.

ABSTRACT

IMPORTANCE: Over 90% of the US population relies on community water supplies (CWS), which generally use chlorine for disinfection. Trihalomethanes are regulated disinfection byproducts associated with bladder cancer and adverse birth outcomes. Animal studies report trihalomethanes, especially brominated compounds, may damage kidney function, but epidemiologic research is limited.

OBJECTIVE: To evaluate long-term exposure to trihalomethanes in residential CWS and its association with chronic kidney disease (CKD) risk.

DESIGN, SETTING, AND PARTICIPANTS: The California Teachers Study (CTS) is an ongoing prospective cohort of female teachers and administrators enrolled between 1995 and 1996 with data linked to mortality and health care records. This cohort study analyzed CTS data from January 1, 2005, once CKD diagnostic coding was adopted, through December 31, 2018. Statistical analysis was conducted from July 2023 to December 2024.

EXPOSURES: Residence time-weighted mean concentrations of 4 trihalomethanes, including 3 brominated trihalomethanes and chloroform, were calculated using annual measurements from CWS serving participants’ homes from 1995 to 2005. Uranium and arsenic (potentially nephrotoxic metals, previously evaluated in the cohort) from CWS were included as part of a g-computation mixture analysis.

MAIN OUTCOMES AND MEASURES: Cases of moderate (stage 3) to end-stage CKD were identified with diagnostic codes or dialysis-related procedures. Mixed-effects multivariable-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for CKD by exposure to trihalomethane levels (US maximum contaminant level of 80 μg/L).

RESULTS: The study sample included 89 320 female participants (median age, 50 years [IQR, 43-61 years]) with 6242 CKD cases. Median concentrations were 5.5 μg/L (IQR, 0.5-24.1 μg/L; 95th percentile, 57.8 μg/L) for total trihalomethanes and 2.7 μg/L (IQR, 0.7-11.3 μg/L; 95th percentile, 30.0 μg/L) for brominated trihalomethanes. In flexible spline-based models, a clear exposure-response association was observed between trihalomethanes and CKD risk, with the highest risk for brominated trihalomethanes. The HRs for CKD risk associated with brominated trihalomethanes at the highest 2 exposure categories (75th percentile and at or above the 95th percentile) were 1.23 (95% CI, 1.13-1.33) and 1.43 (95% CI, 1.23-1.66), respectively (P < .001 for trend). Brominated trihalomethanes were the largest contributor (52.9%) to the association of the overall mixture with CKD risk, followed by uranium (35.4%), arsenic (6.2%), and chloroform (5.5%).

CONCLUSIONS AND RELEVANCE: In this prospective cohort study of California female teachers, exposure to trihalomethane concentrations less than 80 μg/L (US current standard) increased CKD risk, particularly brominated trihalomethanes, which are not separately regulated in community water. The findings may have public health implications given the widespread use of water chlorination and growing burden of CKD.

PMID:40601319 | DOI:10.1001/jamanetworkopen.2025.18513

JAMA Netw Open. 2025 Jul 1;8(7):e2518525. doi: 10.1001/jamanetworkopen.2025.18525.

ABSTRACT

IMPORTANCE: Mobility, defined as the ability to move freely, decreases with increasing age. The increasing frequency and intensity of extreme weather and climate events (EWCEs), such as hurricanes, pose a considerable risk for older adults (aged ≥65 years) to maintain their mobility (ie, mobility resilience).

OBJECTIVE: To examine whether an association exists between older-aged neighborhoods and mobility resilience following an EWCE.

DESIGN, SETTING, AND PARTICIPANTS: This case series study used 2022 demographics with prospectively observed social infrastructure point-of-interest visitations before and after Hurricane Ian (September 23-30, 2022) to characterize neighborhood mobility resilience. Analyses were conducted for all residents (age categories, <36 years, 36-42 years, 43-53 years, >53 years) of central and southern Florida neighborhoods.

MAIN OUTCOMES AND MEASURES: Using a resilience triangle framework, daily point-of-interest visitation data before, during, and after the event were used to measure the duration of recovery, ratio of recovery, ratio of impact, and area of resilience triangles.

RESULTS: Among 1819 neighborhoods including 8 084 335 residents (median [range] of neighborhood ages, 46 [19-82] years; 51% female), a total of 225 218 social infrastructure points of interest with 75.4 million visitation records were included. Compared with younger-aged neighborhoods, neighborhoods in the oldest age quartile had a longer duration of mobility recovery after Hurricane Ian (1.137 days; 95% CI, 0.844-1.431 days), lower mobility recovery ratio (-2.1%; 95% CI, -4.0% to -0.2%), higher ratio of impact (1.2%; 95% CI, 0.3%-2.1%), and higher cumulative losses of daily mobility (17.0 percentage-days; 95% CI, 8.4-26.3 percentage-days). These associations were substantially attenuated by hurricane wind exposure (ie, the strength of the storm) (Lindemann, Merenda, and Gold relative importance, 0.919-0.960 vs 0.031-0.065 for age quartiles).

CONCLUSIONS AND RELEVANCE: In this case series study, neighborhoods with an older population showed compromised mobility resilience associated with the aftermath of Hurricane Ian. These findings may inform neighborhood-targeted mobility interventions for climate resilience.

PMID:40601318 | DOI:10.1001/jamanetworkopen.2025.18525

JAMA Netw Open. 2025 Jul 1;8(7):e2518569. doi: 10.1001/jamanetworkopen.2025.18569.

ABSTRACT

IMPORTANCE: There is a disproportionately high rate of overdose deaths immediately following an emergency department (ED) visit for opioid overdose. Thus, an improved understanding of disparities in ED treatment and referral is vital. Racial and ethnic disparities in access to naloxone and buprenorphine have been described in the outpatient setting but prevalence in the ED setting remains understudied.

OBJECTIVE: To examine racial and ethnic disparities in treatment referral rates in ED patients with opioid overdose.

DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of a prospective consecutive cohort from the Toxicology Investigators Consortium (TOXIC) Fentalog Study from September 21, 2020, to November 11, 2023. Ten hospital sites were a part of the TOXIC network and participants included ED patients in aged 18 years or older with opioid overdose. Data were analyzed from December 2022 to March 2025.

EXPOSURES: Patient race, ethnicity, sex, and other demographic and clinical factors of interest.

MAIN OUTCOMES AND MEASURES: Study outcomes included the proportion of patients receiving a referral to outpatient addiction care and the proportion receiving a naloxone kit or prescription or buprenorphine prescription at discharge. Descriptive statistics were tabulated, and χ2 and multivariable logistic regression analyses were used to evaluate for differences by race, ethnicity, sex, and other demographic and clinical variables.

RESULTS: In this study, 1683 patients met all inclusion criteria (mean [SD] age, 42.5 [14.5] years; 1221 males [72.6%]; 461 females [27.4%]; 447 Black patients [26.6%]; 63 Hispanic patients [4.3%]; 867 White patients [51.5%]). Of the 1683 included patients, 299 (17.8%) received a referral for outpatient treatment, 713 (42.4%) received a naloxone kit or prescription, and 141 (8.4%) received a buprenorphine prescription. Compared with White patients, Black patients had a decreased adjusted odds ratio (aOR) of outpatient treatment referral (aOR, 0.67; 95% CI, 0.47-0.97). Hospital admission was also associated with increased adjusted odds of outpatient treatment referral (aOR, 3.13; 95% CI, 2.34-4.20). Geographic variation was associated with all primary and secondary outcomes.

CONCLUSIONS AND RELEVANCE: In this study, Black patients were less likely to receive outpatient referrals for OUD. These findings underscore the need for targeted interventions to address racial disparities in ED care for OUD, particularly in enhancing referral processes.

PMID:40601317 | DOI:10.1001/jamanetworkopen.2025.18569

JAMA Netw Open. 2025 Jul 1;8(7):e2518826. doi: 10.1001/jamanetworkopen.2025.18826.

ABSTRACT

IMPORTANCE: Neighborhood characteristics may be independently associated with survival after acute myocardial infarction (AMI).

OBJECTIVE: To examine the association of living in a marginalized neighborhood with mortality and care for younger AMI survivors (aged <65 years) in a universal health care system.

DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort using clinical and administrative databases in Ontario, Canada. Participants were younger patients hospitalized for their first AMI who received invasive evaluation and survived to 7 days after discharge between April 1, 2010, and March 1, 2019. Statistical analysis was performed between May 27, 2022, and March 31, 2025.

EXPOSURES: Neighborhood marginalization, a metric comprising material deprivation, residential instability, and dependency.

MAIN OUTCOMES AND MEASURES: All-cause death, all-cause hospitalizations, and subsequent AMIs. Proportional hazards regression models were used to quantify the association of marginalization with outcomes over 3 years.

RESULTS: Among 65 464 AMI patients (median age, 56 [IQR, 50-61] years; 22.9% female), increasing neighborhood marginalization was associated with higher rates of mortality beginning 30 days after discharge and persisting over time. At 3 years, mortality rates ranged from 2.2% in the least marginalized neighborhood quintile (Q1) to 5.2% in the most marginalized (Q5). Adjusted hazard ratios for mortality over 3 years of follow-up were significantly higher in patients from marginalized neighborhoods and ranged from 1.13 (95% CI, 0.95-1.35) in Q2 to 1.52 (95% CI, 1.29-1.80) in Q5. Over 1 year, differences were observed between Q1 and Q5 in visits to primary care physicians (Q1, 96.1%; Q5, 91.6%) and cardiologists (Q1, 88.0%; Q5, 75.7%), as well as diagnostic testing.

CONCLUSIONS AND RELEVANCE: In this cohort study of younger AMI survivors with universal health care, living in marginalized neighborhoods was associated with adverse outcomes. The observed differences in health service utilization among marginalized patients warrant further investigation to better understand the underlying structural and systemic factors.

PMID:40601315 | DOI:10.1001/jamanetworkopen.2025.18826

J Comput Assist Tomogr. 2025 Jul 2. doi: 10.1097/RCT.0000000000001769. Online ahead of print.

ABSTRACT

OBJECTIVE: To construct and validate the optimal model for preoperative prediction of proliferative HCC based on habitat-derived radiomics features of Gd-EOB-DTPA-Enhanced MRI.

METHODS: A total of 187 patients who underwent Gd-EOB-DTPA-enhanced MRI before curative partial hepatectomy were divided into training (n=130, 50 proliferative and 80 nonproliferative HCC) and validation cohort (n=57, 25 proliferative and 32 nonproliferative HCC). Habitat subregion generation was performed using the Gaussian Mixture Model (GMM) clustering method to cluster all pixels to identify similar subregions within the tumor. Radiomic features were extracted from each tumor subregion in the arterial phase (AP) and hepatobiliary phase (HBP). Independent sample t tests, Pearson correlation coefficient, and Least Absolute Shrinkage and Selection Operator (LASSO) algorithm were performed to select the optimal features of subregions. After feature integration and selection, machine-learning classification models using the sci-kit-learn library were constructed. Receiver Operating Characteristic (ROC) curves and the DeLong test were performed to compare the identified performance for predicting proliferative HCC among these models.

RESULTS: The optimal number of clusters was determined to be 3 based on the Silhouette coefficient. 20, 12, and 23 features were retained from the AP, HBP, and the combined AP and HBP habitat (subregions 1, 2, 3) radiomics features. Three models were constructed with these selected features in AP, HBP, and the combined AP and HBP habitat radiomics features. The ROC analysis and DeLong test show that the Naive Bayes model of AP and HBP habitat radiomics (AP-HBP-Hab-Rad) archived the best performance. Finally, the combined model using the Light Gradient Boosting Machine (LightGBM) algorithm, incorporating the AP-HBP-Hab-Rad, age, and AFP (Alpha-Fetoprotein), was identified as the optimal model for predicting proliferative HCC. For the training and validation cohort, the accuracy, sensitivity, specificity, and AUC were 0.923, 0.880, 0.950, 0.966 (95% CI: 0.937-0.994) and 0.825, 0.680, 0.937, 0.877 (95% CI: 0.786-0.969), respectively. In its validation cohort of the combined model, the AUC value was statistically higher than the other models (P<0.01).

CONCLUSIONS: A combined model, including AP-HBP-Hab-Rad, serum AFP, and age using the LightGBM algorithm, can satisfactorily predict proliferative HCC preoperatively.

PMID:40601290 | DOI:10.1097/RCT.0000000000001769

Eur J Epidemiol. 2025 Jul 2. doi: 10.1007/s10654-025-01263-4. Online ahead of print.

ABSTRACT

Concerns about the safety of titanium dioxide (TiO₂), including potential carcinogenicity, have prompted its ban in foods in the European Union, while remaining allowed as pharmaceutical excipient. We aimed to evaluate whether ingesting increasing quantities of TiO₂ through medicines is associated with higher cancer risk. Data were derived from the French National Health Data System, a nationwide medico-administrative database. A case-control study was nested within two cohorts: users of metformin (all doses) and users of 200 mg acebutolol, both available in TiO₂-containing and TiO₂-free formulations. During 2013-2021, 293,101 cancer cases were identified and matched to 2,930,633 controls. TiO₂ exposure through metformin and acebutolol consumption was calculated based on drug claims from 2006 up to five years before the index date. Conditional logistic regression models estimated linear associations between TiO₂ exposure and cancer risk. RRs of overall cancer per 1000 TiO₂-containing tablets and per 10,000 mg of TiO₂ increments were both 1.00 (95% CI: 0.99-1.01). Analyses by cancer site also yielded RRs very close to 1.00 or slightly different but not statistically significant, except for breast (RR per 10,000 mg: 1.03, 95% CI:1.00-1.07) and lymphoid/hematopoietic (RR per 1000 tablets: 0.97, 95% CI: 0.95-1.00) cancers, which however lost significance after Bonferroni correction. There was a suggestion of non-linear positive association for central nervous system cancers. This first epidemiological study on TiO₂ ingestion and cancer found no meaningful linear association between increasing TiO₂ exposure through medicines and overall or site-specific cancer risk. Non-linear associations cannot be excluded.

PMID:40601245 | DOI:10.1007/s10654-025-01263-4

Cell Biochem Biophys. 2025 Jul 2. doi: 10.1007/s12013-025-01817-z. Online ahead of print.

ABSTRACT

In this study, a series of benzoxazole-linked pyrazole compounds (20a-t) were synthesized and tested for their antiproliferative activity. Their effects on lung cancer (A549) and normal lung (CCD-34Lu) cell lines were evaluated using the MTT assay. Among them, compounds 20m and o showed strong antiproliferative effects, with IC₅₀ values of 7.64 and 15.82 µM, respectively, and selectivity indices of 2.84 and 1.95 in favor of cancer cells. ELISA tests demonstrated that both compounds statistically significantly reduced VEGFR-2 protein levels by 24.8 and 28.7% at their respective IC₅₀ values, indicating potential antiangiogenic properties. Molecular docking studies supported these findings by showing favorable binding of 20m and o to the VEGFR-2 receptor, with binding energies of -7.33 kcal/mol and -7.22 kcal/mol, respectively. Overall, compounds 20m and o stand out as promising candidates for further development as anticancer drugs.

PMID:40601229 | DOI:10.1007/s12013-025-01817-z

Geroscience. 2025 Jul 2. doi: 10.1007/s11357-025-01741-3. Online ahead of print.

ABSTRACT

Canagliflozin (Cana) started at 16 months of age and 16-hydroxy-estradiol (OH_Est) started at 12 months each led to significant increases in lifespan in male UM-HET3 mice but significant decreases in female lifespan. To seek insights into the basis for these sex-specific effects, we performed end-of-life histopathological analyses of control and treated mice for all three interventions testing program sites. There were no significant drug-induced alterations in inferred cause of death, although statistical power was low for such comparisons. Tabulation of incidental lesions (i.e., combining lethal and non-lethal lesions) revealed a complex set of significant and near-significant changes caused by each of the two agents, in some cases absent, or even opposite in direction, in one of the two sexes. The analysis did not, however, reveal a clear pattern that would explain the selective sex-specific effects of either agent on lifespan. It is plausible that the female-specific harm induced by each of these agents could reflect harmful or toxic effects that are not easily detectable by histopathological examination.

PMID:40601216 | DOI:10.1007/s11357-025-01741-3

Ann Intensive Care. 2025 Jul 2;15(1):88. doi: 10.1186/s13613-025-01508-1.

ABSTRACT

BACKGROUND: Post-cardiac arrest (CA) care guidelines (GLs) have been introduced in 2010 and periodically updated every 5 years since then (in 2015 and 2021). However, the impact of these GLs on patients’ outcome remains underexplored. The aim of this study was to comprehensively evaluate and compare the impact of implementation of three consecutive post-CA GLs over 14 years, on patients’ survival and neurological recovery.

METHODS: This retrospective cohort study included adult patients resuscitated from CA and admitted to the intensive care unit (ICU) between 2011 and 2024. Patients were stratified into three cohorts based on the GL in use (GL2010, GL2015, and GL2024). Adherence to GL recommendations was assessed across seven macro-areas: coronary angiography, haemodynamic, ventilation, temperature control, general ICU management, multimodal neuroprognostication, and seizure control. Predictors of survival and favourable neurological outcome at ICU discharge were evaluated using multivariate logistic regression with LASSO selection. Outcome up to 6 months was also evaluated.

RESULTS: A total of 275 patients were included over the 14-year period. Survival to ICU discharge increased from 39.5% in cohort 1 to 53.9% in cohort 3, together with favourable neurological outcome that improved from 30.9 to 42.7%. Adherence to GL recommendations significantly improved across most domains, particularly in haemodynamic management (from 32.0% in cohort 1 to 77.3% in cohort 3), temperature control (from 60.6 to 94.4%), and general ICU management (from 56.3 to 77.6%). Among all interventions, adherence to haemodynamic recommendations was independently associated with improved survival (OR = 2.20, 95% CI: 1.01-4.86).

CONCLUSIONS: Following the implementation of updated post-CA care GLs, adherence to recommendations improved, particularly in haemodynamic management. Although no statistically significant improvements in survival or neurological outcomes were observed, these findings highlight the potential value of sustained GL-based care.

PMID:40601206 | DOI:10.1186/s13613-025-01508-1