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Nevin Manimala Statistics

To the editor: Clarifying LSM cutoff validation, statistical power, and subgroup applicability in predicting liver-related events in chronic hepatitis B

Hepatology. 2025 Oct 7. doi: 10.1097/HEP.0000000000001558. Online ahead of print.

NO ABSTRACT

PMID:41056560 | DOI:10.1097/HEP.0000000000001558

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Nevin Manimala Statistics

Retinal Vasculitis and Stroke Risk in Patients with Systemic Lupus Erythematosus

Ocul Immunol Inflamm. 2025 Oct 7:1-6. doi: 10.1080/09273948.2025.2563170. Online ahead of print.

ABSTRACT

PURPOSE: To assess the association between retinal vasculitis and cerebral stroke and mortality in patients with systemic lupus erythematosus (SLE).

METHODS: Patients with SLE with and without retinal vasculitis were identified in the TriNetX research network. Initially, there were 337,411 patients with SLE and no retinal vasculitis and 570 patients with SLE and retinal vasculitis. After matching to balance age, sex, race, and cardiac risk factors, 540 patients remained in each group. Outcomes evaluated included stroke risk and mortality over a 20-year follow-up. Statistical analysis included risk ratios (RR), Kaplan-Meieranalysis, and Cox proportional hazards modeling.

RESULTS: The 1-year stroke risk was 1.9% in patients without retinal vasculitis and 4.5% with retinal vasculitis. At 5 years, risks were 4.7% and 9.1%; at 10 years, 5.6% and 13.2%; and at 20 years, 7.5% and 17.1%, respectively (p < 0.001). The average weighted stroke risk in patients with and without retinal vasculitis was 8.3% and 3.8%, respectively (RR: 2.19, 95% CI: 1.31-3.68, p = 0.002). Cox regression analysis of stroke risk showed a hazard ratio for retinal vasculitis of 2.25 (95% CI: 1.72-2.94, p < 0.001). Mortality rates over 20 years were 6.9% without retinal vasculitis and 8.3% with retinal vasculitis (RR: 1.21, 95% CI: 0.8 – 1.84, p = 0.3626).

CONCLUSIONS: The presence of retinal vasculitis in patients with SLE significantly increases the risk of stroke over a 20-year period, highlighting the importance of early identification and timely referral of this group of patients.

PMID:41056537 | DOI:10.1080/09273948.2025.2563170

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Nevin Manimala Statistics

Comparing Prognostic Value of the Pediatric Glasgow Coma Scale and the Glasgow Coma Scale – Pupils Score in Pediatric Traumatic Brain Injury

J Trauma Nurs. 2025 Sep 30. doi: 10.1097/JTN.0000000000000884. Online ahead of print.

ABSTRACT

BACKGROUND: The Glasgow Coma Scale has been a standard tool for assessing consciousness in trauma patients for five decades, but its utility is limited by the omission of brainstem reflexes such as pupillary response.

OBJECTIVE: This study aimed to compare the prognostic accuracy of the Pediatric Glasgow Coma Scale (pGCS) and the Pediatric Glasgow Coma Scale – Pupils Score (pGCS-P) in predicting mortality and functional outcomes among pediatric patients with traumatic brain injury (TBI).

METHODS: This single-center observational cohort study was conducted from May 2022 to May 2023 at Bursa Training and Research Hospital, Health Sciences University, Turkey. Pediatric patients (age <18 years) presenting with TBI were evaluated for level of consciousness and pupillary responses on admission. Both the pGCS and pGCS-P scores were calculated for each patient. For patients with anisocoria but preserved light reflexes in both pupils, scoring adjustments were made.

RESULTS: Of the 134 patients studied, 59.7% were male, and the mean (SD) age was 6.3 (5.4) years. In-hospital mortality was 12.7%, and 5.1% had unfavorable functional outcomes (UFOs) at discharge. Both the pGCS-P and pGCS demonstrated excellent ability to predict mortality (AUC, 0.97, 95% CI: 0.94-0.99 and 0.97, 95% CI: 0.94-0.96, respectively). There was no statistically significant difference in prognostic performance between the two scores using either binomial (p = .165) or nonparametric (p = .445) analyses (p >.05).

CONCLUSIONS: In pediatric patients with TBI, the prognostic accuracy of the pGCS with pupil response (pGCS-P) was comparable to that of the pGCS alone for predicting mortality and UFOs. Incorporation of the pupil score did not significantly improve prognostic discrimination in this cohort.

PMID:41056536 | DOI:10.1097/JTN.0000000000000884

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Nevin Manimala Statistics

HPV vaccination willingness and behavior among nursing female students in China based on the protection motivation theory: A cross-sectional study

Hum Vaccin Immunother. 2025 Dec;21(1):2569738. doi: 10.1080/21645515.2025.2569738. Epub 2025 Oct 7.

ABSTRACT

Female nursing students show high intention yet low uptake of HPV vaccination, which undermines cervical cancer prevention efforts. To examine the mechanisms influencing their vaccination behavior, this study developed and validated an intention-behavior transition model based on Protection Motivation Theory, thereby providing a theoretical foundation for designing targeted interventions and improving vaccination coverage. A total of 631 female nursing students from universities in Wuhan were selected by the convenience sampling method and were surveyed using a General Information Questionnaire, Protection Motivation Questionnaire, and HPV Vaccination Willingness and Behavior Questionnaire, and a structural equation model was constructed using AMOS 24.0 software. 69.3% of the 631 female nursing students had HPV vaccination intention, and 13.3% had vaccination behavior. The results of structural equation model fitting showed that threat appraisal significantly affected female nursing students’ willingness to receive HPV vaccination (β = 0.209, P < .002) and behavior (β = -0.198, P = .002). Coping appraisal significantly influenced their willingness to vaccinate (β = -0.085, P < .008) and behavior (β = -0.170, P < .001). Willingness to vaccinate significantly influenced vaccination behavior (β = 0.627, P < .001). The Protection Motivation Theory is applicable for explaining the decision-making mechanism regarding HPV vaccination among female nursing students, as both threat appraisal and coping appraisal collectively influence the intention-behavior transition process. This study provides theoretical support for formulating immunization promotion policies targeted at this population; however, future research should expand sample diversity to enhance the generalizability of the findings.

PMID:41056529 | DOI:10.1080/21645515.2025.2569738

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Nevin Manimala Statistics

Immunophenotypic changes in the tumor and tumor microenvironment during progression to multiple myeloma

PLoS Genet. 2025 Oct 7;21(10):e1011848. doi: 10.1371/journal.pgen.1011848. Online ahead of print.

ABSTRACT

Investigation of the cellular and molecular mechanisms of disease progression from precursor plasma cell disorders to active disease increases our understanding of multiple myeloma (MM) pathogenesis and supports the development of novel therapeutic strategies. In this analysis, single-cell RNA sequencing, surface protein profiling, and B lymphocyte antigen receptor profiling of unsorted, whole bone marrow (BM) mononuclear cell samples was used to study molecular changes in tumor cells and the tumor microenvironment (TME). A cell atlas of the BM microenvironment was generated from 123 subjects including healthy volunteers and patients with monoclonal gammopathy of unknown significance (MGUS), smoldering MM (SMM), and MM. These analyses revealed commonalities in molecular pathways, including MYC signaling, E2F targets and interferon alpha response, that were altered during disease progression. Evidence of early dysregulation of the immune system in MGUS and SMM, which increases and impacts many cell types as the disease progresses, was found. In parallel with disease progression, population shifts in CD8 + T cells, macrophages, and classical dendritic cells were observed, and the resulting differences in CD8 + T cells and macrophages were associated with poor overall survival outcomes. Potential ligand-receptor interactions that may play a role during the transition from precursor stages to MM were identified, along with potential biomarkers of disease progression, some of which may represent novel therapeutic targets. MIF, IL15, CD320, HGF and FAM3C were detected as potential regulators of the TME by plasma cells, while SERPINA1 and BAFF (TNFSF13B) were found to have the highest potential to contribute to the downstream changes observed between precursor stage and MM cells. These findings demonstrate that myeloma tumorigenesis is associated with dysregulation of molecular pathways driven by gradually occurring immunophenotypic changes in the tumor and TME. Trial registration: This project has been registered at EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) with protocol number NOPRODMMY0001 and EudraCT Number 2018-004443-23 on 12 December 2018.

PMID:41056512 | DOI:10.1371/journal.pgen.1011848

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Nevin Manimala Statistics

The prevalence of autoimmune hepatitis is rising: Estimates and trends from a large, multi-ethnic cohort in the United States

Hepatol Commun. 2025 Oct 7;9(11):e0824. doi: 10.1097/HC9.0000000000000824. eCollection 2025 Nov 1.

ABSTRACT

BACKGROUND: Large epidemiologic studies of autoimmune hepatitis (AIH) in the United States are limited. None have reported prevalence trends over time. This contemporary study examines AIH prevalence and demographic trends over 10 years in a community-based integrated healthcare system in Northern California. We further assessed whether prevalence trends differed by AIH ascertainment approach.

METHODS: This retrospective study used data from adults aged ≥18 years in Kaiser Permanente Northern California (2010-2019). AIH was identified by coded diagnosis and confirmed with diagnostic testing (laboratory and/or liver biopsy) and treatment response. Annual AIH prevalence was estimated and stratified by age, sex, and race/ethnicity.

RESULTS: Among 1129 patients with confirmed AIH, 80% were female, 44% non-Hispanic White, 26% Hispanic, 16% Asian/Pacific Islander, and 9% Black. In all, 76% of patients on AIH treatment demonstrated treatment response at 6 months. AIH prevalence (per 100,000 adults) increased from 9.1 in 2010 to 18.8 in 2019 (p<0.0001). Prevalence among older adults (≥75 years) quadrupled from 10.1 to 43.7 per 100,000. Prevalence rose among all ethnicities and in 2019 was highest for Black (28.9) and Hispanic populations (25.2) per 100,000.

CONCLUSIONS: AIH prevalence doubled over 10 years in a large healthcare system, with pronounced increases among older populations. Prevalence was highest among Black and Hispanic adults. Further studies should examine demographic differences in the clinical course of AIH, including response to therapy, adverse events, and outcomes.

PMID:41056496 | DOI:10.1097/HC9.0000000000000824

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Nevin Manimala Statistics

Navigating sampling bias in discrete phylogeographic analysis: assessing the performance of an adjusted Bayes factor

Mol Biol Evol. 2025 Oct 7:msaf253. doi: 10.1093/molbev/msaf253. Online ahead of print.

ABSTRACT

Bayesian phylogeographic inference is widely used in molecular epidemiological studies to reconstruct the dispersal history of pathogens. Discrete phylogeographic analysis treats geographic locations as discrete traits and infers lineage transition events among them, and is typically followed by a Bayes factor (BF) test to assess the statistical support. In the standard BF (BFstd) test, the relative abundance of the involved trait states is not considered, which can be problematic in the case of unbalanced sampling. Existing methods to correct sampling bias in discrete phylogeographic analyses using continuous-time Markov chain (CTMC) model, often require additional epidemiological information to balance the sampling effort among locations. As such data is not necessarily available, alternative approaches that rely solely on available genomic data are needed. In this perspective, we assess the performance of a modification of the BFstd, the adjusted Bayes factor (BFadj), which incorporates information on the relative abundance of samples by location when inferring support for transition events and root location inference without requiring additional data. Using a simulation framework, we assess the statistical performance of BFstd and BFadj under varying levels of sampling bias, estimating their type I and type II error rates. Our results show that BFadj complements the BFstd by reducing type I errors at the cost increasing type II errors for inferred transition events, while improving type I and type II errors in root location inference. Our findings provide guidelines for implementing the complementary BFadj to detect and mitigate sampling bias in discrete phylogeographic inference using CTMC modelling.

PMID:41056469 | DOI:10.1093/molbev/msaf253

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Nevin Manimala Statistics

No Consensus on the Consensus: Failure to Adopt Fracture-Related Infection (FRI) Definition at the OTA Annual Meetings

J Orthop Trauma. 2025 Oct 7. doi: 10.1097/BOT.0000000000003092. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the rate at which abstracts accepted for the Orthopedic Trauma Association (OTA) Annual Meeting from 2019 to 2024 utilized the Fracture-related Infection (FRI) Consensus Group’s definition for infection.

METHODS: Data Sources: The data sources for this study included the Orthopedic Trauma Association (OTA) Annual Meeting Programs from 2019-2024 and the “abstract search” portion of OTA Website.

STUDY SELECTION: All podium and poster abstract presentations that utilized keywords for infection (“fracture-related infection,” “infection,” or “SSI”) in the title.

DATA EXTRACTION: All abstracts were reviewed, and grouped into one of the four following categories based on the methodologic descriptors used to define infection characteristics: 1) Utilized Consensus Group Definition, 2) Utilized CDC Definition [deep, superficial, organ/space, or SSI terminology], 3) Utilized an Author Specific Definition, 4) Did Not Utilize Any Definition.

DATA SYNTHESIS: Univariate statistics were conducted to determine yearly and overall percentages of abstracts that utilized the Consensus Group’s definition as compared to the other 3 definition categories. Bivariate analysis was performed to determine if the use of Consensus Group’s definition varied from 2019-2024.

RESULTS: 52 podium abstracts and 59 poster abstracts were included. Among the podium abstracts, 4 (7.7%) utilized the Consensus Group’s definition of FRI, 37 (71.2%) utilized language from the CDC definition, 4 (7.7%) used an author specific definition, and 7 (13.5%) abstracts did not utilize any definition of descriptors of infection. Poster abstracts demonstrated similar utilization of methodical infection descriptors, as 5 (8.5%) utilized the Consensus Group’s definition of FRI. The number of abstracts that utilized the Consensus Group’s Definition did not vary from 2019-2024 (p=0.952 for podiums, p=0.451 for posters).

CONCLUSIONS: Adoption of the FRI Consensus Group’s definition among accepted OTA 2019-2024 Annual Meeting abstracts was low.

LEVEL OF EVIDENCE: IV.

PMID:41056451 | DOI:10.1097/BOT.0000000000003092

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Nevin Manimala Statistics

Comparing long-term effects of different earplug fit-training methods on U.S. Marine Corps training recruits

Int J Audiol. 2025 Oct 7:1-11. doi: 10.1080/14992027.2025.2568647. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the long-term effects of two earplug fit-training methods on the ability of U.S. military personnel to self-fit a foam earplug and achieve sufficient attenuation of weapon noise during military training.

DESIGN: Participants were randomly assigned to one of two earplug fit-training methods (control [typical; n = 239], experimental [experiential hearing protection device (eHPD); n = 151]), and one of two hearing protector fit-testing (HPFT) schedules (quarterly, annually).

STUDY SAMPLE: 390 U.S. Marine Corps Infantry training recruits.

RESULTS: Passing had no association with participants tested quarterly or annually and were merged to two groups for analysis. Immediately post-training, 57% of the control and 78% of the experimental training groups achieved a passing personal attenuation rating (PAR) of at least 25.0 A-weighted decibels. Approximately 12 months post-training, the passing PAR proportion reduced to 19% (control) and 37% (experimental). The differences in pass rates between groups at both time points were statistically significant (p < 0.05).

CONCLUSIONS: The individualised eHPD fit-training resulted in a greater proportion of participants able to achieve adequate noise protection (both immediately and one year later) with issued foam earplugs. Based on our study results, the ability to adequately self-fit in-ear hearing protection is a perishable skill and annual training is justified.

PMID:41056447 | DOI:10.1080/14992027.2025.2568647

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Nevin Manimala Statistics

Effect of Aspirin Versus Low-Molecular-Weight Heparin for Thromboprophylaxis in High-Risk and Fracture Location Subpopulations: A Secondary Analysis of the PREVENT CLOT Trial

J Orthop Trauma. 2025 Oct 6. doi: 10.1097/BOT.0000000000003094. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the effectiveness and safety of aspirin versus low-molecular-weight heparin (LMWH) for thromboprophylaxis in 11 high-risk or fracture location subpopulations.

METHODS: Design: A post-hoc secondary analysis of the published PREVENT CLOT trial.

SETTING: 21 trauma centers.

PATIENT SELECTION CRITERIA: Adult patients with an operatively treated extremity fracture or any pelvic or acetabular fracture were enrolled from April 2017 through August 2021. Patients with only hand or foot fractures, presenting >48 hours after injury, or with a history of VTE within 6 months of injury were excluded. The 11 subpopulations included i) a head injury, ii) an abdominal injury, iii) a spinal injury, iv) a thoracic injury, v) multiply injured patients, vi) obesity, vii) previous VTE ≥ 6 months, viii) isolated upper extremity fracture, ix) isolated lower extremity fracture, x) isolated pelvic or acetabular fracture, and xi) geriatric femur fracture.

OUTCOME MEASURES AND COMPARISONS: The primary outcome was 90-day all-cause mortality. Secondary outcomes included non-fatal pulmonary embolism, proximal deep vein thrombosis (DVT), distal DVT, and bleeding events. Outcomes were assessed using Kaplan-Meier estimators and Cox proportional hazards models comparing 81 mg of aspirin versus 30 mg of LMWH twice daily. The threshold for statistical significance was a Bonferroni-corrected alpha of 0.001 to account for multiple comparisons.

RESULTS: The largest subpopulations were isolated lower extremity fractures (n=6,289), obesity (n=4,234), and polytrauma with Injury Severity Score (ISS) >16 (n=1,596). No comparison of aspirin vs LMWH within the 11 subpopulations for the 5 outcomes reached the corrected threshold for statistical significance of P < 0.001. However, 5 comparisons of aspirin vs LMWH were less than the conventional P-value of 0.05. Specifically, the aspirin group demonstrated lower mortality in patients with a head injury (difference, -3.2%; 95% CI -6.1% to -0.3%; P = 0.03) or a spine injury (difference, -6.0%; 95% CI -11.7% to -0.3%; P = 0.04) than the LMWH group. The LMWH group demonstrated a lower rate of distal DVTs for patients with a head injury (difference, 4.4%; 95% CI, 0.8% to 8.1%; P = 0.03), thoracic injury (difference, 1.5%; 95% CI, 0.0% to 2.9%; P=0.034) or with ISS >16 (difference, 1.7%; 95% CI, 0.2% to 3.3; P = 0.03) than the aspirin group.

CONCLUSIONS: Within 11 high-risk or fracture location-specific subpopulations, there were no statistically significant differences between aspirin or LMWH in the 90-day rates of all-cause mortality, non-fatal PE, proximal DVT, distal DVT, or bleeding complications at a threshold corrected for multiple comparisons (P < 0.001).

LEVEL OF EVIDENCE: Therapeutic Level I.

PMID:41056444 | DOI:10.1097/BOT.0000000000003094