Category: Nevin Manimala

Epilepsia Open. 2025 Aug 18. doi: 10.1002/epi4.70123. Online ahead of print.

ABSTRACT

OBJECTIVE: Early recurrence of epileptic seizures within the same day of emergency department (ED) admission poses clinical management challenges. While several blood-based parameters have been proposed as prognostic markers in various neurological disorders, their predictive utility in same-day seizure recurrence remains underexplored. We aimed to investigate whether inflammatory parameters derived from hemogram parameters can predict seizure recurrence within the same day in patients presenting with epileptic seizures or not.

METHODS: We included 267 patients who presented to our ED with epileptic seizures within the last 2 years. Patients were grouped into recurrence (n = 68) and non-recurrence (n = 199) cohorts. Hemogram-derived indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), monocyte-to-neutrophil ratio (MNR), platelet-to-neutrophil ratio (PNR), immune-platelet inflammation value (IPIV), pan-immune inflammation value (PIV), systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were calculated and compared between groups. Statistical analyses included receiver operating characteristic (ROC) curve assessment for predictive accuracy.

RESULTS: NLR, PLR, SII, and SIRI values were significantly elevated in the recurrence group (p < 0.05), indicating heightened systemic inflammation. Traditional parameters such as white blood cell count (WBC), glucose, and lactate did not significantly differ. Area under the curve (AUC) values in ROC curve analyses revealed that the NLR (AUC = 0.618) and SII (AUC = 0.601) had moderate discriminative ability, although no parameter achieved a substantial predictive value (AUC ≥ 0.7).

SIGNIFICANCE: Elevated inflammatory indices, particularly NLR and SII, are associated with same-day seizure recurrence, suggesting their potential utility in ED triage. However, none demonstrated sufficient stand-alone predictive power, highlighting the need for prospective studies incorporating novel biomarkers.

PLAIN LANGUAGE SUMMARY: This study looked at whether certain blood test values can help predict if a person who comes to the emergency department (ED) with an epileptic seizure will have another seizure on the same day. Researchers focused on inflammation-related markers found in routine blood tests, such as the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). We found that these values were higher in patients who had repeated seizures within the same day. However, while these markers showed some association with seizure recurrence, they were not accurate enough to reliably predict it on their own. These findings suggest that simple blood tests might provide helpful clues in emergency settings, but more research is needed to find stronger and more reliable indicators for early seizure recurrence.

PMID:40824701 | DOI:10.1002/epi4.70123

Indian J Pathol Microbiol. 2025 Aug 14. doi: 10.4103/ijpm.ijpm_290_25. Online ahead of print.

ABSTRACT

INTRODUCTION: Molecular subtyping of urothelial cancer of the bladder can help in identifying aggressive subtypes and aid in the prognostication of the disease. These subtypes can be broadly identified with the help of immunohistochemistry (IHC) markers reliably.

AIMS: To assess the molecular subtypes of urothelial carcinoma of the bladder using IHC markers and evaluate their association with clinicopathological characteristics and overall survival (OS).

MATERIALS AND METHODS: This was a cross-sectional study done over 3 years in a tertiary care center. There were 109 cases of invasive urothelial carcinoma of the bladder. In 43 cases, radical cystectomy was performed, and 66 cases underwent transurethral resection of bladder tumor. CK5/6, and CK14 were used as markers of the basal subtype; GATA-3 and CK20 were used for the luminal subtype. Cases were classified into basal, luminal, double-positive, and double-negative subtypes. The association of molecular subtypes with clinicopathological characteristics was analyzed. OS was analyzed for the molecular subtypes. All the relevant statistical tests were performed using IBM SPSS software version 24.0.

RESULTS: The most frequently occurring molecular subtype was luminal (GATA3+, CK5/6-) in 62% of cases. Tumors with the basal subtype showed a higher frequency of muscle invasion compared to nonbasal types and presented as high-grade tumors. The luminal subtype was significantly associated with conventional histology and lamina propria invasive tumors. The basal molecular subtype showed a mean OS of 15 (±4) months, which was significantly worse than that of nonbasal subtypes.

CONCLUSION: The basal subtype of urothelial carcinoma of the bladder behaves more aggressively in terms of grade, extent of invasion, and OS.

PMID:40824692 | DOI:10.4103/ijpm.ijpm_290_25

JAMA Pediatr. 2025 Aug 18. doi: 10.1001/jamapediatrics.2025.2585. Online ahead of print.

ABSTRACT

IMPORTANCE: Previous studies have suggested that removing financial barriers to contraception could help reduce unintended pregnancy.

OBJECTIVE: To assess whether introduction of universal public funding for prescription contraception in Ontario (OHIP+) for individuals younger than 25 years and the amended program, which limited public funding to those without private insurance (OHIP-), is associated with changes in contraceptive dispensations.

DESIGN, SETTING, AND PARTICIPANTS: Interrupted time-series analyses were used to evaluate whether implementation of either policy was associated with changes in monthly contraceptives dispensed. The setting included a national database on contraceptives dispensed from retail pharmacies between September 2016 and February 2020; data analysis was performed from May 2022 to 2024. Participants included Ontario females aged 15 to 24 years to whom prescriptions were dispensed (intervention) vs controls: (1) Canadian females aged 15 to 24 years, excluding Ontario, and (2) Ontario females aged 25 to 49 years.

EXPOSURES: Implementation of free prescription contraception through OHIP+ (January 2018-March 2019) and OHIP- (April 2019-February 2020).

MAIN OUTCOMES AND MEASURES: Monthly dispensations of intrauterine devices (IUDs) and oral contraceptive pills (OCPs) per 1000 females overall and by area-level socioeconomic status (SES).

RESULTS: After OHIP+, there was an immediate level increase in IUDs dispensed to Ontario females aged 15 to 24 years (intervention) of 0.50 (95% CI, 0.15-0.84) vs 0.03 (95% CI, -0.26 to 0.32) in Canadian females aged 15 to 24 years-a relative increase of 0.48 (95% CI, 0.02-0.91). There was an immediate level increase in OCPs dispensed to Ontario females aged 15 to 24 years of 22.3 (95% CI, 14.8-29.8) vs 7.57 (95% CI, 3.07-12.1) in those aged 25 to 49 years-a relative increase of 14.8 (95% CI, 6.15-23.4). There were no statistically significant changes in monthly dispensation trends after OHIP+ and no statistically significant changes after OHIP-. In areas with lower SES, there was a significant increase in the level for IUDs of 0.64 (95% CI, 0.02-1.26) and for OCPs of 13.2 (95% CI, 1.33-25.0) after OHIP+, and a significant decrease in the level for IUDs of 0.82 (95% CI, -1.55 to -0.09) after OHIP- in Ontario vs Canadian females aged 15 to 24 years. No statistically significant changes in IUD or OCP dispensations were observed in areas with higher SES vs controls.

CONCLUSIONS AND RELEVANCE: Results reveal that providing comprehensive and confidential access to prescription contraceptives was associated with increased dispensations among Ontario youth.

PMID:40824678 | DOI:10.1001/jamapediatrics.2025.2585

JAMA Netw Open. 2025 Aug 1;8(8):e2527148. doi: 10.1001/jamanetworkopen.2025.27148.

ABSTRACT

IMPORTANCE: Mass azithromycin distributions may reduce malaria parasitemia in the short term, but longer-term effectiveness is unclear.

OBJECTIVE: To examine whether biannual mass azithromycin distributions are associated with lower rates of malaria parasitemia in preschool children living in Niger.

DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized trial was performed from November 23, 2014, until June 9, 2020, as an ancillary trial to a larger trial studying the effect of mass azithromycin on child mortality. Study communities (ie, government-defined health catchment areas) in Niger were randomized in a 1:1 ratio to biannual (ie, twice-yearly) mass administration of azithromycin or placebo to all children aged 1 to 59 months and followed up for 5 years. Data analyses were performed from June 25, 2023, to April 27, 2025.

INTERVENTION: Twice-yearly administration of a single dose of oral azithromycin, 20 mg/kg, or placebo.

MAIN OUTCOMES AND MEASURES: The prevalence of parasitemia 4 years after the community started treatment, assessed in a random sample of 40 children per community.

RESULTS: Among the 30 communities in Niger included in the study at baseline, the 15 communities randomized to azithromycin consisted of 1695 children (mean [SD] age, 30.8 [2.8] months; 858 [51.8%] male) and the 15 communities randomized to placebo consisted of 3031 children (mean [SD] age, 30.6 [2.6] months; 157 [52.0%] male). The mean prevalence of malaria parasitemia at baseline was 8.9% (95% CI, 5.1%-15.7%) in the azithromycin arm and 6.7% (95% CI, 4.0%-12.6%) in the placebo arm. At annual follow-up visits up until month 48, parasitemia was not statistically significantly lower in the azithromycin arm compared with the placebo arm, assuming a 10% prevalence in the placebo arm (-3.3 percentage points [PP]; 95% CI, -5.8 to -0.2 PP; permutation P = .05). The Niger Ministry of Health instituted seasonal malaria chemoprevention (SMC) after the month 36 study visit. Analysis restricted to the period before SMC found significantly less parasitemia in the azithromycin arm compared with the placebo arm (4.8 PP lower; 95% CI, -7.4 to -1.3 PP; permutation P = .02).

CONCLUSIONS AND RELEVANCE: In this placebo-controlled cluster randomized trial, malaria among children aged 1 to 59 months was lower in communities treated with biannual mass azithromycin, but the effect was significant only for the first 3 years of the trial, before SMC.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02048007.

PMID:40824641 | DOI:10.1001/jamanetworkopen.2025.27148

JAMA Netw Open. 2025 Aug 1;8(8):e2527418. doi: 10.1001/jamanetworkopen.2025.27418.

ABSTRACT

IMPORTANCE: Buprenorphine is a first-line medication for opioid use disorder, yet many individuals face barriers to filling buprenorphine prescriptions. Telemedicine patients may have prescriptions questioned and rejected more frequently due to being perceived as a diversion risk due to their prescriber’s physical distance from the pharmacy.

OBJECTIVE: To evaluate pharmacy challenges in filling buprenorphine prescriptions among adults receiving telemedicine treatment for opioid use disorder overall and by rural and nonrural residence.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed a web-based survey conducted from August to September 2024. Adult patients receiving treatment from a telemedicine practice providing low-barrier treatment for opioid use disorder in 5 US states were included. Participants were identified through electronic health records; inclusion criteria were diagnosis of opioid use disorder, enrollment in telemedicine treatment with a valid zip code, and completion of a new evaluation visit and follow-up appointment.

EXPOSURE: Rural and nonrural residence determined by patient zip codes mapped to Rural-Urban Commuting Area codes.

MAIN OUTCOMES AND MEASURES: Self-reported frequency of buprenorphine fill problems in the past year, types of fill problems, and days without buprenorphine due to pharmacy-related challenges.

RESULTS: A total of 601 patients participated, with 300 (49.9%) residing in nonrural areas, 363 (60.4%) identifying as women, and a mean (SD) age of 41.44 (8.60) years. Nearly one-third of patients (192 [31.9%]) had to go without buprenorphine due to a pharmacy-related barrier in the past 12 months, and more than one-quarter (165 [27.5%]) reported having problems filling their buprenorphine prescription. There was no statistically significant difference in the experience of buprenorphine fill problems between rural and nonrural respondents. The most common problems were that buprenorphine was unavailable and needed ordering (90 of 165 [54.5%]), insurance coverage-related barriers (37 [22.4%]), and pharmacy hesitancy in filling a telemedicine prescription (32 [19.4%]).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of patients receiving telemedicine treatment for opioid use disorder, challenges filling buprenorphine prescriptions were prevalent and led to concerning periods when patients were untreated and at an increased risk of returning to nonprescribed opioid use. There is a critical need for interventions to ensure sufficient access to buprenorphine, including implementing buprenorphine stocking requirements and medication delivery services through collaborating pharmacies.

PMID:40824639 | DOI:10.1001/jamanetworkopen.2025.27418

JAMA Netw Open. 2025 Aug 1;8(8):e2527455. doi: 10.1001/jamanetworkopen.2025.27455.

ABSTRACT

IMPORTANCE: The incidence of central precocious puberty (CPP) is increasing globally, raising concern about its potential long-term health consequences. However, the association between early-life feeding practices and CPP is poorly understood.

OBJECTIVE: To investigate the association of breastfeeding during the first 4 to 6 months of life with CPP in boys and girls and whether this association is mediated by prepubertal adiposity.

DESIGN, SETTING, AND PARTICIPANTS: This nationwide, retrospective cohort study used health claims data from the South Korean National Health Insurance Service Database between January 1, 2007, and December 31, 2020. Children who underwent routine health checkups at 4 to 6 months (examination 1) and 66 to 71 months (examination 7) were eligible. Children with comorbidities, who died during the follow-up period, who had missing information, or who were diagnosed with CPP before age 6 years were excluded. Data were analyzed between October 9, 2024, and January 14, 2025.

EXPOSURE: Feeding practice patterns collected through a primary caregiver-reported questionnaire during examination 1.

MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of CPP, defined by International Statistical Classification of Diseases, Tenth Revision diagnostic codes and administration of gonadotropin-releasing hormone agonists. The association between feeding practices and incidence of CPP was assessed using a multivariable Cox proportional hazards model to estimate adjusted hazard ratios (AHRs) and 95% CIs. Causal mediation analysis within a counterfactual framework was conducted to quantify mediation by childhood overweight or obesity.

RESULTS: Among 322 731 children (58.1% girls), 46.0% were exclusively breastfed, 34.9% were formula-fed, and 19.1% were mixed-fed. Compared with exclusively breastfed children, formula-fed children had the greatest risk of CPP in boys (AHR, 1.16; 95% CI, 1.10-1.21) and girls (AHR, 1.60; 95% CI, 1.24-2.06), followed by mixed-fed boys (AHR, 1.14; 95% CI, 1.07-1.20) and girls (AHR, 1.45; 95% CI, 1.07-1.97). Mediation through prepubertal adiposity accounted for 7.2% (bootstrap 95% CI, 4.5%-12.1%) and 17.8% (bootstrap 95% CI, 6.6%-30.0%) of the association between formula feeding and CPP in boys and girls, respectively.

CONCLUSIONS AND RELEVANCE: In this nationwide, retrospective cohort study, breastfeeding during the first 4 to 6 months of life was associated with a lower risk of CPP in boys and girls. This association was partially mediated by prepubertal adiposity, highlighting the critical role of early-life nutrition in pubertal timing.

PMID:40824636 | DOI:10.1001/jamanetworkopen.2025.27455

J Pers Soc Psychol. 2025 Aug 18. doi: 10.1037/pspa0000459. Online ahead of print.

ABSTRACT

Discrimination remains a key challenge for social equity. A prerequisite for effective individual and societal responses to discrimination is that instances of it are detected. Yet, prejudice and discriminatory intent are rarely directly observable and the presence of discrimination has to be inferred from circumstantial evidence, such as the over- or underrepresentation of certain individuals (i.e., statistical bias). Here, we study how people judge outcomes that are statistically biased along different dimensions. Six primary and two supplemental studies with Dutch and U.S. participants (total N = 3,591, six preregistered) show that gender- and race-biased outcomes are perceived as much less fair than unbiased outcomes, but we do not observe the same for attractiveness-biased outcomes. While this pattern is partly explained by differences in the perceived legitimacy of different biases (i.e., people judge attractiveness bias as more acceptable than gender and race bias), we also find consistent evidence for an additional mechanism. People spontaneously pay attention to a few salient dimensions, such as gender and race, when scrutinizing decision outcomes for bias. Statistical bias along less salient dimensions, such as physical attractiveness, is more likely to go undetected. Our findings suggest that the (seeming) tolerance of attractiveness-biased outcomes is partly explained by people’s failure to spontaneously notice that the outcome is attractiveness-biased in the first place. In other words, it is possible that people show muted responses to a biased outcome not because they actually approve of it, but because they fail to notice the bias. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40824619 | DOI:10.1037/pspa0000459

AMB Express. 2025 Aug 18;15(1):120. doi: 10.1186/s13568-025-01932-3.

ABSTRACT

While gut microbiome associations with sporadic Creutzfeldt-Jakob disease (sCJD) are recognized, causal mechanisms and mediation via cerebrospinal fluid (CSF) metabolites remain unestablished. Using bidirectional Mendelian randomization (MR) with mediation analysis and integrating genome-wide association study (GWAS) summary statistics from gut microbiota (​​composition in the FINRISK 2002 prospective cohort, n = 5,959​​), CSF metabolites (from the Wisconsin Alzheimer’s Disease Research Center ​​Registry and Wisconsin Registry for Alzheimer’s Prevention​​, n = 291), and sCJD case-control data (5,208 cases vs. 511,675 controls), we identified five microbial taxa influencing sCJD risk. Protective effects were observed for the family Atopobiaceae [odds ratio (OR) = 0.527, 95% confidence interval (CI) = 0.321-0.864, P = 0.011], the species Enterococcus faecalis (OR = 0.647, 95% CI = 0.427-0.980, P = 0.040), and the genus Lactobacillus (group B) (OR = 0.768, 95% CI = 0.602-0.981, P = 0.035). Conversely, the species Bacteroides eggerthii (OR = 1.228, 95% CI = 1.027-1.468, P = 0.025) and the order Chloroflexales (OR = 3.455, 95% CI = 1.214-9.835, P = 0.020) were pathogenic. Mediation analysis revealed that S-methylcysteine mediates 8.8% of ​​the effect of order Chloroflexales on sCJD risk​​, establishing it as a significant biological mediator in this pathogenic pathway. These findings provide novel biomarkers for early sCJD risk stratification, identify ​​the family Atopobiaceae, the species Enterococcus faecalis, and the genus Lactobacillus (group B)​​ as probiotic candidates for primary prevention, reveal S-methylcysteine pathway modulation as therapeutic entry points, and establish mechanistic foundations for disrupting gut-CSF transmission​​ in prion diseases.

PMID:40824609 | DOI:10.1186/s13568-025-01932-3

Tech Coloproctol. 2025 Aug 18;29(1):163. doi: 10.1007/s10151-025-03204-5.

ABSTRACT

BACKGROUND: Total mesorectal excision (TME) remains the oncologic standard for rectal cancer surgery; however, technical challenges persist in the minimally invasive treatment of low rectal cancer. Transanal TME (TaTME) and robotic TME were developed to overcome the limitations of laparoscopic TME in confined pelvic spaces. Despite promising results, comparative evidence among these approaches remains limited and heterogeneous. To address this gap, we conducted a propensity score-matched analysis to evaluate and compare the clinical and oncologic outcomes of TaTME, robotic TME, and laparoscopic TME in patients with rectal cancer treated at a high-volume tertiary center.

METHODS: This retrospective study included patients with rectal cancer who underwent restorative proctectomy between 2015 and 2021. Propensity score matching was used to balance demographic, clinical, and treatment variables across the three groups. Outcomes were analyzed using standard statistical methods.

RESULTS: After matching, 240 patients were included (40 TaTME, 40 robotic TME, and 160 laparoscopic TME). TaTME and robotic TME demonstrated significantly lower overall complication rates than laparoscopic TME (27.5% versus 20.0% versus 39.4%, p = 0.033). The circumferential resection margin positivity rate was highest in the laparoscopic group (10.6% versus 0% versus 2.5%, p = 0.031). However, 5-year overall survival (82.5% versus 85.0% versus 88.1%, p = 0.251), disease-free survival (75.0% versus 72.5% versus 73.8%, p = 0.772), local recurrence (17.5% versus 12.5% versus 24.7%, p = 0.488), and distal metastasis (17.5% versus 22.5% versus 25.2%, p = 0.694) did not significantly differ among groups.

CONCLUSIONS: All three minimally invasive TME techniques achieved comparable long-term oncologic outcomes. Surgical approach should be tailored on the basis of surgeon expertise and patient-specific factors.

PMID:40824598 | DOI:10.1007/s10151-025-03204-5

Appl Health Econ Health Policy. 2025 Aug 18. doi: 10.1007/s40258-025-00992-7. Online ahead of print.

ABSTRACT

OBJECTIVES: Despite an increasing number of mapping studies being conducted in China, there is an absence of a systematic reviews, which makes it difficult to inform the applications and further assess the methodological consistency, accuracy, and applicability of existing mapping studies. The objective of this review is to consolidate existing evidence, identify methodological gaps, and provide recommendations for improving mapping studies conducted among the Chinese population.

METHODS: A systematic literature search was conducted in 14 databases from inception to May 31, 2025 to identify studies that developed mapping algorithms to estimate health utility values, specifically among Chinese populations. A data template was applied to extract dataset information, source and target measures, mapping types (direct vs indirect), models used, goodness-of-fit indicators, validation methods, and the optimal mapping algorithms selected. Potential challenges for future related studies were further discussed.

RESULTS: A total of 33 studies was included. Most studies (87.9%) focused on mapping disease-specific non-preference-based measures (PBMs) to generic PBMs. The studies covered a broad range of disease areas, including oncology (36.4%), musculoskeletal disorders (15.2%), metabolic diseases (15.2%), cardiovascular diseases (9.1%), and neurological conditions (6.1%). All studies used direct mapping, with the ordinary least squares model (n = 37) being used most frequently, followed by Tobit model (n = 32) and Beta model (n = 22). Eleven studies explored indirect mapping, with the Ordered Logit and Ordered Probit models being the most employed techniques. Thirty-two studies conducted internal validation, with the N-fold cross-validation being the most used method-no study conducted external validation. The sample size ranged from 133 to 3320, with a median sample size of 553. Conducted conceptual analysis was performed in 81.8% of the studies to assess the degree of overlap between the source measure and target measure; 72.7% of the studies reported the utility/score distributions, and 15.2% of studies further reported the response distributions.

CONCLUSION: This systematic review provides insights into methodologies employed in mapping studies in China and identifies key areas for improvement. Addressing issues related to sample size, conceptual overlap, model selection, and validation methods will enhance the quality and applicability of mapping algorithms, ultimately supporting more robust cost-utility analyses in the Chinese healthcare system.

PMID:40824559 | DOI:10.1007/s40258-025-00992-7