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Nevin Manimala Statistics

ProAE: an R package for graphical tools and standardized analysis of patient-reported outcomes and adverse events data

BMC Med Inform Decis Mak. 2025 Dec 20. doi: 10.1186/s12911-025-03320-0. Online ahead of print.

ABSTRACT

BACKGROUND: Patient-reported symptomatic adverse events (AE) are increasingly collected in oncology clinical trials to characterize treatment tolerability and inform clinical decision making using the Patient-Reported Outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®). Although there are numerous analysis methods and graphical approaches used for PRO-CTCAE data, the current PRO literature is limited in unified reporting and graphical approaches as well as public-facing analysis tools.

RESULTS: Collaborative efforts from the Standardization Working Group of the National Cancer Institute Cancer Treatment Tolerability Consortium worked to develop the R package, ProAE. Testing and validation of widely used methods were implemented in the R package and deployed to various open-source outlets including the Comprehensive R Archive Network (CRAN).

CONCLUSION: ProAE is a free and publicly available collection of standardized statistical analysis tools for PRO-CTCAE and other PRO data used in patient care and research. The ProAE package provides oncology researchers with an efficient and modern means to apply the published analysis approaches, including hypothesis testing, descriptive and inferential tables, and longitudinal graphics, without the need for costly software or licensing.

PMID:41422214 | DOI:10.1186/s12911-025-03320-0

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Nevin Manimala Statistics

Type of information source and healthcare avoidance: insights from two population-based studies during the COVID-19 pandemic

BMC Public Health. 2025 Dec 20. doi: 10.1186/s12889-025-25927-8. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic generated major disruptions in primary and specialist care, and there were global trends of reduced healthcare-seeking behaviour. Previous studies showed that use of information sources is linked to psychological well-being and compliance with public health measures. It is unclear if the type of information source is also associated with healthcare avoidance.

METHODS: Between April and October 2020, we sent a questionnaire to participants of two population-based cohort studies including middle-aged and older adults from Rotterdam, the Netherlands: the Rotterdam Study (N = 8,732, response rate 71.5%) and the Generation R Study (N = 4,904, response rate 22.7%). We defined healthcare avoidance as not seeking care despite experiencing symptoms that participants would otherwise interpret as requiring medical attention. We pooled the data from both studies and used logistic regression analyses to examine the adjusted association between type and number of information sources and healthcare avoidance. Additionally, we investigated if symptoms of depression and anxiety modified and/or mediated this association.

RESULTS: Among 6,702 respondents (mean age 67.0 years, 61.8% women), 96.0% used traditional media, 15.5% used social media, and 1,197 (17.9%) avoided healthcare. Compared to non-avoiders, avoiders more often reported poor/fair self-appreciated health (28.9% versus 9.7%), and symptoms of depression (31.9% versus 11.6%) or anxiety (29.2% versus 11.1%). Odds of healthcare avoidance were lower for those who consulted traditional media (adjusted OR (aOR): 0.72, 95% CI: 0.53-1.00) and higher among individuals using social media (aOR: 1.21, 95% CI: 1.02-1.44), compared to those who did not use these sources. Additional adjustment for self-appreciated health and anxiety/depressive symptoms attenuated the latter association. Stratified analyses showed a stronger association between social media use and healthcare avoidance among individuals with anxiety symptoms (aOR: 1.34, 95% CI: 0.94-1.89), yet not statistically significant. Additionally, in a fully adjusted model, part of the association between social media and healthcare avoidance was mediated by anxiety symptoms, although the effect estimate of the mediated effect was small (p-value 0.14, natural indirect effect OR: 1.03, 95% CI: 1.01-1.05).

CONCLUSIONS: Social media use was associated with higher odds of healthcare avoidance as compared to not using social media, whereas use of traditional media was related to lower avoidance. We found suggestive evidence for a role of anxiety symptoms in these associations, which should be validated by future studies. These findings emphasise the importance of disseminating accessible, objective information across a variety of media platforms, where needed tailored to vulnerable populations, to support informed decision-making during and beyond health crises.

PMID:41422209 | DOI:10.1186/s12889-025-25927-8

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Nevin Manimala Statistics

Prevalence and antimicrobial resistance of Escherichia coli and Klebsiella spp in dairy farm in the Tigray Region, Northern Ethiopia

BMC Microbiol. 2025 Dec 20. doi: 10.1186/s12866-025-04643-8. Online ahead of print.

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) in animal-derived food is a significant global health issue, especially in low- and middle-income countries where sanitation, responsible antibiotic use, and surveillance remain weak. In dairy farming, Escherichia coli (E. coli) and Klebsiella species are of particular concern as they frequently exhibit multidrug resistance and produce extended-spectrum β-lactamase (ESBL). Despite their growing public health significance, limited data exist on their distribution in Ethiopia, particularly in the Tigray region. Therefore, this study aimed to determine the prevalence and antimicrobial resistance profiles of E. coli and Klebsiella spp. in dairy farm environments in the Tigray region of northern Ethiopia.

METHODS: A cross-sectional study was conducted between December 2024 and May 2025, analyzing 712 samples from raw bulk tank milk, milk-container swabs, water, and milkers’ stool, each 178. Escherichia coli and Klebsiella spp. were isolated and identified using standard culture and biochemical tests. Antimicrobial susceptibility was determined by the disk diffusion method according to CLSI (2024), and ESBL production was confirmed using the phenotypic double-disk synergy test (DDST). Isolates resistant to one or more antibiotics in three or more antimicrobial classes were classified as Multi-Drug Resistant (MDR). Data were processed and analyzed using SPSS version 26.

RESULTS: Out of 712 samples, 494 (69.4%) were positive for either E. coli or Klebsiella spp., with E. coli (49.6%) predominating over K. pneumoniae (10.3%) and K. oxytoca (9.6%). High resistance levels were observed to tetracycline (62.9%), amoxicillin/clavulanic acid (31.2%), and trimethoprim-sulfamethoxazole (27.7%), while resistance to meropenem remained low (2.4%). Overall, 32.4% of isolates were MDR, with the highest rates in E. coli (32.0%). ESBL production was detected in 53 (10.7%) of isolates, across all sample types and locations.

CONCLUSION: The study revealed a high prevalence of E. coli and Klebsiella spp. in dairy farm environments, with a considerable proportion of MDR and ESBL producers. This poses a serious concern for food safety and public health. These findings highlight the urgent need to enhance hygiene, antimicrobial stewardship, and integrated One Health-based surveillance along the dairy value chain.

PMID:41422193 | DOI:10.1186/s12866-025-04643-8

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Nevin Manimala Statistics

Cross-platform comparison of gene expression-based cancer molecular subtyping reveals discrepancies with exome capture methods

NPJ Precis Oncol. 2025 Dec 20. doi: 10.1038/s41698-025-01228-6. Online ahead of print.

ABSTRACT

Gene expression profiling in precision oncology is increasing with uncertain validity across platforms. In this study, we examined the application of PurIST, a molecular subtyping algorithm for pancreatic ductal adenocarcinoma (PDAC), across different platforms. We compared PurIST calls between matched samples processed by whole transcriptome and commercial exome capture RNA-seq. In parallel, we compared subtypes between matched samples processed by NanoString and whole transcriptome RNA-seq from the PANCREAS trial (NCT04683315). Between whole transcriptome and exome capture, subtype agreement was 81% with significant increase in basal-like subtype with exome capture. Differences in overall survival in patients with basal-like tumors compared to classical tumors did not reach statistical significance using exome capture (log-rank P = 0.061), whereas with whole transcriptome it was significantly shorter (log-rank P < 0.0001). Subtype agreement between whole transcriptome RNA-seq and NanoString was higher at 95%. PurIST results should be interpreted with caution when using exome capture methods.

PMID:41422185 | DOI:10.1038/s41698-025-01228-6

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Nevin Manimala Statistics

Body mass index and a body shape index: Individual and interactive predictors of all-cause and cardiovascular mortality risk in depression

Psychiatry Res. 2025 Dec 14;356:116907. doi: 10.1016/j.psychres.2025.116907. Online ahead of print.

ABSTRACT

OBJECTIVE: Conflicting evidence exists on the association of obesity, depression and mortality risk. This study evaluates a cohort of subjects with depression from the USA NHANES and all-cause and cardiovascular mortality risks based on baseline BMI and ABSI.

METHODS: A nationally representative cohort study was conducted using NHANES data (2005-2018), including 2854 adults with depression. Weighted Cox regression and restricted cubic spline (RCS) models were applied to assess anthropometric associations with mortality. Weighted receiver operating characteristic (ROC) curves evaluated the diagnostic value of BMI and ABSI.

RESULTS: Each 1-SD BMI increase was predictive of reduced all-cause (HR = 0.81, 95 % CI:0.67-0.98) and cardiovascular mortality (HR = 0.62, 95 % CI:0.43-0.89). Each 1-SD ABSI increase was predictive of elevated all-cause (HR = 1.27, 95 % CI:1.06-1.51) and cardiovascular mortality (HR = 1.60, 95 % CI:1.20-2.15). In these depressed individuals, BMI showed the U-shaped and ABSI the expected curvi-linear relationships with mortality as established from the studies of the NHANES cohorts. In ROC analyses, ABSI showed the best predictive performance for all-cause mortality (AUC = 0.678) and for cardiovascular mortality (AUC = 0.706). BMI Tertile 1 & ABSI Tertile 3 had the highest mortality risks (all-cause HR = 3.09, 95 % CI:1.38-6.93; cardiovascular HR = 5.45, 95 % CI:1.36-21.85). Due to the approximate statistical independence of BMI and ABSI, combining them further improved AUC values (all-cause: 0.691; cardiovascular: 0.722).

CONCLUSION: Among individuals with depression ABSI predicts mortality similar to the general population, while obesity as defined by BMI was “paradoxically” associated with lower mortality. Personalized mortality risk for an individual can be derived by combining the independent risks based on BMI and ABSI.

PMID:41420910 | DOI:10.1016/j.psychres.2025.116907

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Nevin Manimala Statistics

MRA morphologic study of the vertebrobasilar artery system in patients with primary hemifacial spasm

Neuro Endocrinol Lett. 2025 Dec 16;46(6):356-365. Online ahead of print.

ABSTRACT

PURPOSE: This study assessed the efficacy of 3.0T magnetic resonance angiography (MRA) in individuals with primary hemifacial spasm (pHFS) by investigating the relationship between alterations in the morphology of the vertebrobasilar artery system and pHFS.

METHODS: A comparison was made between pHFS patients and healthy controls with respect to vertebral artery diameter, displacement rate, and other relevant parameters to explore the potential role of morphologic abnormalities in the vertebrobasilar arteries in the pathogenesis of pHFS. Independent t-tests and Wilcoxon rank-sum tests were used with statistical significance set at a p < 0.05.

RESULTS: A total of 100 pHFS patients and 150 healthy participants underwent 3.0T MRA scans for this analysis. The right vertebral artery (VA) diameter in the pHFS group was larger than the healthy control (HC) group (2.71 mm vs. 2.47 mm; p < 0.05) and the left VA deviation distance in the pHFS group was greater than the HC group (7.99 mm vs. 5.27 mm; p < 0.05). The basilar artery deviation distance in the pHFS group was greater than the HC group (7.41 mm vs. 4.78 mm; p < 0.05). The VA deviation rates in the pHFS group were significantly higher than the HC group (89% vs. 72% and 96% vs. 84.67%, respectively; p < 0.05). The VA scores on the symptomatic and non-symptomatic sides were significantly different (p < 0.05). VA migration increased with age (p = 0.034, r = 0.225).

CONCLUSION: The results imply a potential association between morphologic irregularities in the vertebrobasilar arteries and pHFS. Limitations of the study included substantial missing data for displacement measurements (64%-67%), age differences between groups, and selection bias from the surgical population.

PMID:41420884

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Mediation Mendelian Randomization Analysis of the Effect of Immune Cells on Autism Spectrum Disorder Mediated by Inflammatory Factors

Neuro Endocrinol Lett. 2025 Dec 16;46(6):315-322. Online ahead of print.

ABSTRACT

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that impairs communication. Increasing research indicates that maternal immune activation (MIA) is one of the most important environmental factors that increase the risk of autism spectrum disorder (ASD) in offspring. Maternal immune activation produces elevated cytokine levels that cross the placental barrier and disrupt fetal neurodevelopment, increasing ASD risk. However, the specific causal pathways and mediating mechanisms remain unclear, limiting our understanding.

METHODS: This mediation Mendelian randomization study examined causal pathways linking immune cell traits (exposures) and inflammatory factors (mediators) to ASD risk.The research merged immune data (731 phenotypes + 48 cytokines) and ASD data from a cohort comprising 18,382 cases and 27,969 controls. Various MR approaches were used to reduce potential biases, along with thorough descriptions of statistical procedures and instrumental variable selection.

RESULTS: The study’s findings propose potential causal relationships among cytokines representing inflammatory factors, immune cells, and ASD through mediation Mendelian randomization. Reverse MR was then employed to investigate the possibility of reverse causality. CD8+ T cell %leukocyte (OR = 1.099, 95% CI: 1.039-1.163, p = 0.001), CCR2+ CD62L+ myeloid dendritic cells (OR = 0.933, p = 0.029), and CD45+ immature myeloid-derived suppressor cells (OR = 1.056, p = 0.001) showed evidence of causal association with ASD risk.Furthermore, reduced Artemin levels and elevated FLT3L and 2B4 levels were significantly linked to ASD risk, indicating that abnormalities in immunomodulatory factors may play a crucial role in the pathogenesis of ASD. Additionally, ASD occurrence may result in alterations in Natural Killer cell receptor 2B4 levels.

CONCLUSION: This mediation Mendelian randomization study provides evidence that immune dysfunction is associated with ASD pathophysiology through inflammatory mediators, requiring functional validation before clinical application.Cytokines act as mediators in the pathogenesis of ASD, providing a theoretical basis for understanding its immunoinflammatory pathogenesis and offering insight into treatment.

PMID:41420879

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Nevin Manimala Statistics

Characterization of gut microbiomes in rural Honduras reveals uncharacterized species and associations with human genetic variation

Cell Rep. 2025 Dec 18;45(1):116724. doi: 10.1016/j.celrep.2025.116724. Online ahead of print.

ABSTRACT

The gut microbiome is integral to human health, yet research data to date have emphasized industrialized populations. Here, we performed large-scale shotgun metagenomic sequencing on 1,893 individuals from rural Honduras, providing the most comprehensive microbiome dataset from Central America. We identify a distinct microbial composition enriched in Prevotella species. Longitudinal analysis in 301 individuals reveals microbiome instability, with shifts in taxonomic diversity and metabolic potential, including changes associated with severe acute respiratory syndrome coronavirus 2 infection. Additionally, we characterize the gut virome and eukaryotic microbiome, identifying uncharacterized viral taxa and a high prevalence of Blastocystis species in individuals with greater microbial diversity. Finally, by integrating host genomic data, we uncover significant host-microbiome associations, highlighting the influence of human genetic variation on microbial composition. These findings expand our understanding of microbiome diversity in non-industrialized populations, underscoring the need for global microbiome research.

PMID:41420859 | DOI:10.1016/j.celrep.2025.116724

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Nevin Manimala Statistics

Association of race and survival in patients treated with apalutamide: Pooled analysis of two phase 3 trials

Cancer. 2026 Jan 1;132(1):e70236. doi: 10.1002/cncr.70236.

ABSTRACT

BACKGROUND: Clinical studies have shown that outcomes of patients with prostate cancer could vary depending on race. In this study, the authors sought to determine if the treatment effect of apalutamide, an androgen receptor pathway inhibitor (ARPI), on overall survival (OS) varies depending on the race of the patient.

METHODS: This pooled analysis includes individual patient data from two phase 3 trials, TITAN and SPARTAN, which randomized patients to androgen deprivation therapy (ADT) ± apalutamide in metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer, respectively. Race was self-identified and categorized as Asian, Black, White, and Others categories. The authors applied a stratified (stratification for the trial) multivariable Cox proportional hazards regression model to determine heterogeneity of treatment effect on OS after adjustment for age, performance status, body mass index, T- and N-stage, Gleason score, comorbidities, and exposure to statins and metformin.

RESULTS: Overall, 2190 patients were included: 16.9% patients were Asian, 3.7% were Black, 67.4% were White, and 12.0% were from the Others category. The authors did not find any significant heterogeneity of treatment effect from apalutamide on OS across racial groups (interaction-p = .46). Among ADT plus apalutamide-treated patients, there was no association of race with OS (hazard ratio for Asian, 0.77 [95% CI, 0.56-1.06]; Black, 0.82 [95% CI, 0.49-1.37]; and Others, 1.00 [95% CI, 0.75-1.34], all compared to White).

CONCLUSIONS: In this study, the authors did not find any evidence of difference in the treatment effect of apalutamide on OS across patients of different races, although interpretation remains limited by poor representation of racial minorities. Among apalutamide-treated patients, there was no association of race with OS.

PMID:41420831 | DOI:10.1002/cncr.70236

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Incidence of ventral hernia surgery after laparoscopic bariatric surgery in Sweden: a registry-based study 2009-2019

Hernia. 2025 Dec 20;30(1):43. doi: 10.1007/s10029-025-03547-w.

ABSTRACT

PURPOSE: The incidence of trocar site hernia (TSH) after bariatric surgery is unclear. This study aims to describe the cumulative incidence of ventral hernia surgery after laparoscopic bariatric surgery in total and by laparoscopic method (LRYGB; Roux-en-Y Gastric Bypass and LSG; Sleeve Gastrectomy).

METHODS: This was a register based observational study on patients subjected to laparoscopic bariatric surgery (LRYGB or LSG) in Sweden 2009-2019. The Scandinavian Obesity Surgery Registry (SOReg) was linked to the Swedish National Patient Register (NPR) to obtain instances of ventral hernia surgery. Nearby codes were used as proxies for TSH surgery, since a specific procedure code for TSH surgery is lacking.

RESULTS: In 64 124 patients, mean follow-up was 67 ± 36 months, LRYGB (n = 52 020) 74 ± 34 months and LSG (n = 12 104) 34 ± 22 months. Mean time between bariatric- and ventral hernia surgery was 36 ± 28 months (range 0-129). The five-year cumulative incidence of surgery for ventral hernia was 2.9% (CI 2.8-3.1). The probability of having hernia surgery was significantly higher for LRYGB compared to LSG (Breslow test, p < 0.001), still significant with differences in follow-up time accounted for (p < 0.001).

CONCLUSION: The incidence of surgery for ventral hernia after laparoscopic bariatric surgery is not negligible in this material covering over a decade of bariatric procedures. Ventral hernia surgery was more common after gastric bypass than after sleeve gastrectomy.

PMID:41420786 | DOI:10.1007/s10029-025-03547-w