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Nevin Manimala Statistics

Racial Diversity and Co-Mutational Analysis of Biologically Relevant Alterations in EGFR Mutant Lung Cancers

Clin Lung Cancer. 2025 Feb 14:S1525-7304(25)00038-5. doi: 10.1016/j.cllc.2025.02.008. Online ahead of print.

ABSTRACT

BACKGROUND: EGFR alterations have significant therapeutic implications in lung cancer (LCa), yet their prevalence and co-mutational patterns in African American populations remain understudied. This study analyzes EGFR-mutant LCa across races using the Tempus database.

METHODS: De-identified records sequenced via Tempus xT assay, (595 to 648 gene DNA panel) were included if they had ≥ 1 pathogenic EGFR mutation (short variants (SVs), copy number amplifications (CNAs), or fusions). Race was determined based on recorded clinical records. Co-mutations were restricted to genes with ≥ 5% frequency in at least 1 race. Statistical analyses were performed using chi-squared tests with Bonferroni or false discovery rate adjustments for multiple testing.

RESULTS: Among 17,482 LCa samples, EGFR alterations occurred in 8.9% of CA, 7.6% of BAA, 39% of API, 15% of other races, and 12% of unknown races. Exon 19 deletions (P = .017) and L858R mutations (P < .001) varied by race, with higher L858R frequency in CA compared to BAA (P = .034) and in API compared to CA (P = .006). EGFR copy number variants (CNVs) were highest in BAA (P < .001). TP53 alterations occurred at a higher frequency in patients with a history of smoking, those with high tumor mutational burden (TMB), and high PD-L1. KMT2C co-mutations were significantly more common in BAA (13%) compared to CA (3%) and API (4%) (q = 0.003). Similarly, GLI1 co-mutations were most frequent in BAA (5.8%) compared to 1.5% in CA and 0% in API patients (q = 0.025).

CONCLUSIONS: EGFR mutation subtypes and co-mutations differ by race. KMT2C may influence TMB and immunotherapy response, while GLI1 is linked to TKI resistance. TP53 alterations were more commen in smokers, and patients with high PDL-1 and TMB, highlighting additional factors that drive tumors with these alterations.

PMID:40064574 | DOI:10.1016/j.cllc.2025.02.008

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Nevin Manimala Statistics

Opposite causal effects of type 2 diabetes and metformin on Alzheimer’s disease

J Prev Alzheimers Dis. 2025 Mar 9:100129. doi: 10.1016/j.tjpad.2025.100129. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) is commonly co-morbid with Alzheimer’s disease (AD). However, it remains unclear whether T2D itself or the antidiabetic drug metformin contributes to the progression of AD.

OBJECTIVE: This study aimed to investigate the overall and independent effects of T2D and metformin use on the risk of AD.

METHODS: Summary genome-wide association study datasets were utilized for the Mendelian randomization (MR) and multivariable MR (MVMR) analyses, including ones for T2D (N = 455,017), metformin (N = 456,276), and AD (N = 453,733). Additionally, using the proportional imbalance method, we analyzed AD-related adverse drug events in the FDA Adverse Event Reporting System (FAERS) database (covering Q1 2004 to Q2 2024).

RESULTS: Our two-sample MR analysis indicated that T2D is not associated with the risk of AD (OR: 1.03, CI: 0.99-1.08, P = 0.128). However, while not statistically significant, genetic signature for metformin exposure demonstrated a trend toward an increased risk of AD (OR: 1.05, CI: 1.00-1.09, P = 0.053). Interestingly, in MVMR analysis, which evaluates independent effects of T2D and metformin exposure on T2D, we found a robust association of T2D with a decrease in the risk of AD (OR: 0.82, CI: 0.68-0.98, P = 0.031), while the use of metformin was associated with a higher risk of AD (OR: 1.26, CI: 1.06-1.50, P = 9.45E-3). In the FAERS database, a total of 228,283 metformin-related adverse event reports from 67,742 cases were found. For metformin as the target drug and AD as the target adverse event, signal analysis reported 29 cases of AD (ROR: 0.83, 95 % CI: 0.58-1.19, P = 0.3126).

CONCLUSIONS: Our study reveals the opposite independent causal effects of T2D and metformin exposure on AD. These findings highlight the importance of assessing AD risk when prescribing metformin to patients with T2D.

PMID:40064559 | DOI:10.1016/j.tjpad.2025.100129

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Nevin Manimala Statistics

Bidirectional Associations Between Attitudes to Aging and Quality of Life for the Older Adults in the Nursing Home: The Contemporaneous and Cross-Lagged Panel Network Analyses

Nurs Health Sci. 2025 Mar;27(1):e70078. doi: 10.1111/nhs.70078.

ABSTRACT

This study examines the relationship between attitudes to aging and quality of life (QoL) among nursing home residents during “chaotic period” (within 6-8 weeks of older adults move into nursing homes) and “adjustment period” (after “chaotic period” until the third month) from a dimensional level using contemporaneous and cross-lagged panel network analyses. A total of 268 older adults completed two rounds of surveys, including the General Information Questionnaire, the Attitudes to Aging Questionnaire, and the WHO Quality of Life-Brief. Psychosocial loss-psychological health and physical change-physical health were the strongest edges during the “chaotic period” and “adjustment period,” respectively. The cross-lagged network revealed that QoL significantly predicted attitudes to aging, and the most influential dimension was environmental health. Findings suggest that there is a need to support older adults in psychologically adapting to life in nursing homes quickly during the “chaotic period” and to assist those experiencing negative physical change during the “adjustment period” by encouraging physical activity. The cross-lagged panel network indicates that we need to help older adults rapidly familiarize themselves with new surroundings when they first move into nursing homes.

PMID:40064545 | DOI:10.1111/nhs.70078

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Nevin Manimala Statistics

Healthcare utilisation and characteristics of adults with fetal alcohol syndrome: a descriptive population-based cohort study in Ontario, Canada

J Intellect Dev Disabil. 2025 Mar 10:1-14. doi: 10.3109/13668250.2025.2449677. Online ahead of print.

ABSTRACT

BACKGROUND: Adults with Fetal Alcohol Syndrome (FAS) experience many adverse health and social outcomes, yet their healthcare utilisation is under-researched.

METHOD: This population-based descriptive cohort study utilised ICES provincial administrative health databases and Canadian Death Vital Statistics to identify adults with FAS via usage of hospital-based services (2002-2013) and examine their demographics, healthcare utilisation, mental health and addiction diagnoses, and mortality during follow-up (2014-2017).

RESULTS: 565 adults with FAS were included in the cohort. During the follow-up period, 27% used in-patient psychiatric care; 30% the emergency department 12 + times; 28% were hospitalised at least once; and 17% used home care services. They displayed high rates of physical and mental health comorbidities, substance use disorders, history of abuse, and income from social assistance.

CONCLUSION: Adults with FAS require accessible and extensive healthcare services to address their complex needs and improve long-term outcomes.

PMID:40064542 | DOI:10.3109/13668250.2025.2449677

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Nevin Manimala Statistics

A Latent Class Analysis of Resilience and Its Relationship With Care Burden and Psychological Distress in Family Caregivers of Older Adults With Disability

Nurs Health Sci. 2025 Mar;27(1):e70069. doi: 10.1111/nhs.70069.

ABSTRACT

Given the challenging circumstances of aging with disability, family caregivers (FGs) face significant strain. Resilience, however, is a crucial protective factor against adverse caregiving outcomes. The study thus aimed to determine the latent classes of resilience among FGs and examine how these classes are related to care burden and psychological distress. This was a cross-sectional descriptive study that included 248 FGs in China. Latent class analysis was conducted to determine the classes of resilience exhibited by FGs. The study revealed four distinct classes of resilience: the high resilience class, high tenacity but moderate strength-optimism class, moderate resilience but low autonomy class, and low resilience class. FGs with secondary caregivers and those who were older were more likely to be part of the high resilience class. Furthermore, caregivers in the high resilience class had significantly lower burdens, less psychological distress, and greater resilience. Therefore, family caregivers’ resilience can be classified according to characteristics; more attention should be given to caregivers who are younger and lack the support of secondary caregivers; and targeted interventions should be developed based on resilience classification characteristics.

PMID:40064541 | DOI:10.1111/nhs.70069

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Nevin Manimala Statistics

Nurses’ Performance as a Mediator Between Nurses’ Fatigue and Patient Safety Culture: A Structural Equation Model Analysis

Nurs Open. 2025 Mar;12(3):e70168. doi: 10.1002/nop2.70168.

ABSTRACT

AIM: To determine the relationships among nurses’ fatigue, nurses’ performance and patient safety culture.

DESIGN: Cross-sectional study.

METHODS: A multicentre study was conducted with 308 nurses working in 14 medical and surgical wards from four teaching hospitals in Iran. The sampling method was stratified with a proportional allocation. Data were collected via a demographic form, the Occupational Fatigue/Exhaustion Recovery (OFER-15), the Nurse Performance Instrument (NPI) and the Hospital Survey on Patient Safety Culture (HSOPSC). The data were analysed via structural equation modelling (SEM).

RESULTS: Nurse fatigue was significantly inversely related to performance and patient safety culture (p < 0.001). Path analysis revealed that each unit of reducing nurses’ fatigue improved patients’ safety culture by 0.286 units and that each unit of improved nurse performance improved patients’ safety culture by 0.360 units. Additionally, each one-unit increase in a nurse’s fatigue could decrease his or her performance by 0.860 units. SEM analysis confirmed the mediating effect of nurses’ performance on the relationship between their level of fatigue and patient safety culture.

PRACTICE IMPLICATIONS: The proposed model can assist nursing managers and healthcare policymakers in developing practical strategies to mitigate and reduce nurses’ fatigue and, consequently, improve nurses’ performance and patient safety.

PATIENT OR PUBLIC CONTRIBUTION: All participants contributed to this research by completing self-reported scales.

PMID:40064530 | DOI:10.1002/nop2.70168

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Nevin Manimala Statistics

Association of clonal haematopoiesis with heart failure incidence and outcomes: A systematic review and meta-analysis

Eur J Heart Fail. 2025 Mar 10. doi: 10.1002/ejhf.3637. Online ahead of print.

ABSTRACT

AIMS: Clonal haematopoiesis (CH) is recognized as a significant risk factor for various non-haematologic conditions, including cardiovascular diseases. However, recent studies examining its relationship with heart failure (HF) have reported conflicting findings. To address these inconsistencies, the present meta-analysis aimed to evaluate the association of CH with the incidence and clinical outcomes of HF.

METHODS AND RESULTS: MEDLINE, Cochrane Library and Scopus were searched until 12 December 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using three-level mixed-effects meta-analyses. Participants (n = 57 755) with CH had significantly greater risk of new-onset HF compared to the non-CH group (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.35, p < 0.0001; I2 = 0%), irrespective of a prior history of coronary artery disease. CH was also correlated with a higher risk of the composite outcome of all-cause mortality and hospitalization for HF (HHF) compared to the non-CH group in patients with established HF (HR 1.84, 95% CI 1.25-2.70, p = 0.002; I2 = 0%). Specifically, CH was associated with a 95% higher risk of all-cause mortality (HR 1.95, 95% CI 1.54-2.47, p < 0.0001; I2 = 0%), with a 3% increase in risk for every 1% increase in variant allele fraction. Participants with concomitant HF and CH had a 56% higher risk of HHF compared to non-CH HF patients (HR 1.56, 95% CI 1.05-2.33, p = 0.029; I2 = 19%).

CONCLUSION: Clonal haematopoiesis is associated with an increased risk of incident HF and worse prognosis in individuals affected by HF. These findings highlight the potential of CH to contribute to a deeper understanding of HF, improve risk stratification, and support more personalized approaches to its management.

PMID:40064512 | DOI:10.1002/ejhf.3637

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Nevin Manimala Statistics

Outcomes for people experiencing homelessness with COVID-19 presenting to emergency departments in Canada, compared with housed patients

CMAJ. 2025 Mar 10;197(9):E236-E243. doi: 10.1503/cmaj.241282.

ABSTRACT

BACKGROUND: Whether people experiencing homelessness (PEH) have different COVID-19 outcomes than housed patients in Canada remains unclear. We sought to ascertain whether rates of in-hospital mortality, hospital admission, critical care admission, and mechanical ventilation differed between PEH and housed people with symptomatic SARS-CoV-2 infection.

METHODS: We conducted a propensity score-matched cohort study to compare the outcomes of PEH and housed patients presenting to emergency departments for acute symptomatic COVID-19. We used data from the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) registry. Covariates in our propensity score model included age, sex, comorbidities, substance use, vaccination status, previous do-not-resuscitate documentation, hospital type, province and calendar quarter of presentation to the emergency department, symptom duration, and severity of illness on presentation.

RESULTS: We found no difference in mortality for PEH (3%) compared with a propensity score-matched cohort of housed patients (3%) (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.43-1.74). We also found no difference in admission rates for PEH (44%) versus housed patients (45%). There was a reduced rate of critical care admission for PEH compared with housed patients (OR 0.66, 95% CI 0.44-1.00), and a trend toward decreased use of mechanical ventilation for PEH versus housed patients, which was not significant (OR 0.60, 95% CI 0.35-1.02).

INTERPRETATION: We found no difference in mortality for PEH with COVID-19 compared with those who were housed. A signal for reduced critical care admission among PEH may reflect differential treatment unrelated to clinical characteristics that we matched for. Future research on resource allocation during pandemics could shed light on potential inequities for vulnerable populations and how best to address them.

PMID:40064502 | DOI:10.1503/cmaj.241282

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Nevin Manimala Statistics

Exploring the potential of Trichoderma secondary metabolites against Tetranychus urticae (Acari: Tetranychidae)

J Invertebr Pathol. 2025 Mar 8:108299. doi: 10.1016/j.jip.2025.108299. Online ahead of print.

ABSTRACT

This study aimed to determine 1) the effects of fungal filtrates containing secondary metabolites from five different isolates of four different Trichoderma species (Trichoderma afroharzianum, T. guizhouense, T. harzianum, and T. virens) grown in different liquid media [malt extract broth (MEB), potato dextrose broth (PDB), yeast peptone glucose (YPG), minimal medium (MM), czapek-dox broth (CDB)] on Tetranychus urticae female, and 2) the effects of Trichoderma filtrates obtained from YPG liquid media on the different biological stages of T. urticae in Petri dish and pot experiments. Results showed that the Trichoderma filtrates produced in the YPG medium exhibited the highest mortality rate of 67.6-83.1 % against T. urticae females at 7 days post-application (dpa) compared to other media. In Petri dish experiments, the mortality rates of Trichoderma filtrates on egg, larva, protonymph and deutonymph stages of T. urticae at 7 dpa were 54.0-57.8 %, 71.5-76.0 %, 72.5-79.8 % and 72.8-80.8 %, respectively. Significant differences were observed between the Trichoderma species and control (P < 0.01) but not among the Trichoderma species (P > 0.05). Trichoderma afroharzianum (83 %) and T. virens (84 %) showed the highest mortality rate on T. urticae adult females at 7 dpa and statistically significant differences were observed among Trichoderma species. Pot experiments revealed that the number of viable T. urticae eggs and mobile stages was significantly lower for T. afroharzianum (110.3 eggs, 105.8 mobile stages) and T. virens (118.5 eggs, 115.3 mobile stages) compared to the control (518.9 eggs, 452.5 mobile stages) at 7 dpa. Significant differences were observed between Trichoderma species and control, but not between T. afroharzianum and T. virens. These findings suggest that Trichoderma secondary metabolites are highly effective against economically important pest such as T. urticae, demonstrating their potential as bio-acaricides. Future research should focus on identifying the specific acaricidal compound(s) within these filtrates.

PMID:40064463 | DOI:10.1016/j.jip.2025.108299

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Nevin Manimala Statistics

Ensuring internal quality control practices in medical Laboratories: IFCC recommendations for practical applications based on ISO 15189:2022

Clin Chim Acta. 2025 Mar 8:120240. doi: 10.1016/j.cca.2025.120240. Online ahead of print.

ABSTRACT

This document describes the guidance on implementing and monitoring an IQC strategy that fulfills the requirements of the Standard ISO 15189:2022. It also explores the practical application of these principles in daily IQC processes within medical laboratories. The goal is to provide a practical, user-friendly resource that not only explains the Standard’s requirements but also equips laboratory professionals with the tools and knowledge needed to enhance diagnostic reliability. To support laboratory professionals in this task, this document follows the structure and content of the ISO 15189:2022 Standard and provides a risk-based approach in consideration of the practical needs for quantitative results. Specific aspects such as the selection and assessment of IQC materials, the definition of control frequency, the definition of acceptable limits, the application of statistical rules, results from different sources comparability and strategies for handling non-conformities, quality indicators and determination of uncertainty of measurement are discussed in depth. Where relevant, excerpts from the ISO 15189:2022 Standard are included, with clarifications and actionable recommendations to facilitate implementation. This document focuses on the crucial role of IQC in the accreditation process, particularly in the identification of risks, their mitigation through corrective actions and the implementation of improvements to prevent errors and control potential risks in the medical laboratory, ensuring patient safety in daily practice.

PMID:40064457 | DOI:10.1016/j.cca.2025.120240