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Nevin Manimala Statistics

Predicting venous thromboembolism among hospitalized adults: a protocol for development and validation of an implementable real-time prognostic model

Diagn Progn Res. 2025 Sep 8;9(1):19. doi: 10.1186/s41512-025-00205-8.

ABSTRACT

BACKGROUND: Hospital-acquired venous thromboembolism (HA-VTE) is a leading cause of morbidity and mortality among hospitalized adults. Numerous prognostic models have been developed to identify those patients with elevated risk of HA-VTE. None, however, has met the necessary criteria to guide clinical decision-making. This study outlines a protocol for refining and validating a general-purpose prognostic model for HA-VTE, designed for real-time automation within the electronic health record (EHR) system.

METHODS: A retrospective cohort of 132,561 inpatient encounters (89,586 individual patients) at a large academic medical center will be collected, along with clinical and demographic data available as part of routine care. Data for temporal, geographic, and domain external validation cohorts will also be collected. Logistic regression will be used to predict occurrence of HA-VTE during an inpatient encounter. Variables considered for model inclusion will be based on prior demonstrated association with HA-VTE and their availability in both retrospective EHR data and routine clinical care. Least absolute shrinkage and selection operator (LASSO) with tenfold cross-validation will be used for initial variable selection. Variables selected by the LASSO procedure, along with those deemed necessary by clinicians, will be used in an unpenalized multivariable logistic regression model. Discrimination and calibration will be reported for the derivation and validation cohorts. Discrimination will be measured using Harrell’s C statistic. Calibration will be measured using calibration intercept, calibration slope, Brier score, integrated calibration index, and visual examination of non-linear calibration curve. Model reporting will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines for clinical prediction models using machine learning methods (TRIPOD + AI).

DISCUSSION: We describe methods for developing, evaluating, and validating a prognostic model for HA-VTE using routinely collected EHR data. By combining best practices in statistical development and validation, knowledge engineering, and clinical domain knowledge, the resulting model should be well suited for real-time clinical implementation. Although this protocol describes our development of a model for HA-VTE, the general approach can be applied to other clinical outcomes.

PMID:40916049 | DOI:10.1186/s41512-025-00205-8

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Injectable contraceptive continuation and user experiences in Punjab, Pakistan: a non-randomized prospective cohort study protocol

BMC Womens Health. 2025 Sep 7;25(Suppl 1):427. doi: 10.1186/s12905-025-03969-9.

ABSTRACT

BACKGROUND: Evidence from multiple pilots and post-introduction scale-up initiatives have demonstrated that self-administered subcutaneous depot-medroxyprogesterone acetate (DMPA-SC) has potential to improve contraceptive continuation rates and expand contraceptive access to populations with limited utilization of facility-based health services. Only a few of these studies have been conducted in South Asian countries, and none where most contraceptive use is of non-hormonal methods that require limited to no contact with the health system, leaving policymakers in countries like Pakistan with limited context-specific evidence to guide decisions on whether, how, and for whom to introduce DMPA-SC.

METHODS: A prospective cohort study will be conducted in 41 health facilities and surrounding communities in Punjab, Pakistan. The primary objective of the study is to compare the 12-month contraceptive continuation rate for women who receive DMPA-SC with that for women who receive intramuscular depot-medroxyprogesterone acetate (DMPA-IM). The secondary objectives are to compare characteristics and experiences of participants who opt for DMPA-SC with those of women who opt for DMPA-IM, which must be administered by a health worker. Additionally, a sub-study is planned to assess how well women opting for self-injection of DMPA-SC adhere to standards for commodity storage, injection timing, injection technique and waste disposal.

DISCUSSION: This research offers an opportunity to contribute to global efforts to reduce inequities in access to contraceptive method choices, while generating actionable evidence to inform health sector decision-making in Pakistan. Although study sites are limited to health facilities where a woman’s first self-injection of DMPA-SC is supervised by a nurse, midwife, medical officer, Lady Health Visitor, Family Welfare Worker or Family Welfare Councilor, the research protocol and findings will provide a foundation for future studies testing alternative service provision and self-injection support models.

TRIAL REGISTRATION: Registered on clinicaltrials.gov as an observational study (NCT05774626).

PMID:40916043 | DOI:10.1186/s12905-025-03969-9

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Access to contraceptive services during the COVID-19 pandemic: clients’ perspective at primary health care level from India, Nigeria and Tanzania

Reprod Health. 2025 Sep 7;22(Suppl 3):159. doi: 10.1186/s12978-025-02123-w.

ABSTRACT

BACKGROUND: The COVID-19 pandemic disrupted the provision of sexual and reproductive health services, including contraceptive and family planning (FP) services. The World Health Organization conducted a multi-country study in India, Nigeria and Tanzania to assess the impact of the pandemic on the health system’s capacity to provide contraceptive and FP services. In this paper, we share the results of a qualitative study aimed at understanding clients’ perspectives at the primary healthcare level on accessing contraceptive services in COVID-19-affected areas in the three aforementioned countries.

METHODS: We conducted interviews with 644 clients seeking contraceptive services across 11, 6 and 33 primary health facilities in India, Nigeria and Tanzania. A total of 44 focus group discussions (FGDs) and 128 in-depth interviews were conducted with clients at the facility and 22 FGDs within the community. Data collection took place from May 2022 to August 2022. Ethical approval was obtained from the WHO Ethics Review Committee and national regulatory bodies. All interviews were analysed using the general approach of content analysis.

RESULTS: Clients at primary health care facilities faced several challenges in accessing contraceptive services. These challenges were grouped into two main categories. The first was related to the unprepared health system (supply), such as a shortage of health workers, stock out of contraceptives or high cost of FP services. The second category was outside the remit of the health system and included insufficient knowledge amongst clients about the availability of FP services, socio-cultural issues like spousal and in-laws’ dominance on decision making, restriction in movement due to lockdown and fear of COVID-19 infection.

CONCLUSIONS: This study highlights the obstacles clients faced in accessing contraceptives during the COVID-19 pandemic in Nigeria, India, and Tanzania. To address these barriers in future crises, ministries of health must establish functional emergency preparedness across all healthcare levels. These plans should prioritize both on the sufficient number/gender of skilled health providers and the availability of contraceptives till the last mile. Utilizing e-health can help keep communities well informed on where, how and when to avail FP services during such emergencies. Health educational programs should actively engage men to gain further support.

PMID:40916041 | DOI:10.1186/s12978-025-02123-w

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Diet-microbiome synergy: unraveling the combined impact on frailty through interactions and mediation

Nutr J. 2025 Sep 7;24(1):135. doi: 10.1186/s12937-025-01201-w.

ABSTRACT

OBJECTIVE: This study analyzed data from the US population to examine how oral microbiome diversity and diet quality individually and synergistically affect frailty.

METHODS: This study included 6,283 participants aged 20 years or older from the 2009-2010 and 2011-2012 NHANES cycles. A frailty index (FI) consisting of 36 items was developed, with items related to nutritional status excluded. The diversity of the oral microbiome was assessed using α-diversity, including observed ASVs, the Shannon-Weiner index, Faith’s phylogenetic diversity (PD), and the Simpson index. Dietary quality was assessed using Dietary Inflammatory Index (DII), Dietary Approaches to Stop Hypertension (DASH), Mediterranean Diet Score (MED), and Alternate Healthy Eating Index (AHEI). Multivariable logistic models were employed to examine the separate and combined associations of oral microbiome diversity and four dietary quality scores with FI, with interaction effects were explored. Several subgroup analyses and sensitivity analyses were conducted to assess the robustness of our findings. Furthermore, the mediation analysis was used to explore oral microbiome diversity as a mediator in the relationship between dietary scores and FI.

RESULTS: Both oral microbiome diversity and dietary quality scores showed significant individual associations with FI. Jointly, those in the highest tertile of oral microbiome diversity and the lowest tertile of DII had lower FI [βObserved ASVs (95% CI) = -2.544(-3.678,-1.411); βFaith’s PD (95% CI) = -2.688(-3.783,-1.593); βShannon-Weiner index (95% CI) = -2.359(-3.333,-1.386); βSimpson index (95% CI) = -1.93(-2.879,-0.981)], compared to participants in the lowest tertile of oral microbiome diversity and the highest tertile of DII. A significant interaction between oral microbiome diversity (Observed ASVs and Faith’s PD) and DII in relation to FI reduction was found (P for interactionObserved ASVs*DII = 0.032, P for interactionFaith’s PD*DII = 0.014). Other dietary scores showed similar joint associations of oral microbiome diversity with FI, but no significant interactions were observed. Further mediation analysis indicated that the proportion of DII’s effect on FI mediated through Observed ASVs, Faith’s PD, and the Shannon-Weiner index was 8.7%, 7.5%, and 3.4%, respectively.

CONCLUSION: This study demonstrates that a high-quality diet and greater α-diversity of oral microbiota are significantly associated with a reduced risk of frailty. Notably, the interaction between DII and the diversity of the oral microbiota exerts a particularly substantial influence on frailty risk.

PMID:40916036 | DOI:10.1186/s12937-025-01201-w

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Associations between comorbid conditions with mild cognitive impairment and Alzheimer’s disease by race-ethnicity and sex based on NACC data

Alzheimers Dement. 2025 Sep;21(9):e70650. doi: 10.1002/alz.70650.

ABSTRACT

INTRODUCTION: We investigated the associations between diabetes (type 2), hypertension and hypercholesterolemia with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) diagnoses by race-ethnicity and sex.

METHODS: Data (n = 22,950) were derived via the National Alzheimer’s Coordinating Center. Logistic regression was used to assess the relationship between each comorbid condition and MCI and AD.

RESULTS: For non-Hispanic White (NHW) and non-Hispanic Black (NHB) males, diabetes and hypertension had a significant positive association with MCI. For NHW females, diabetes, hypertension, and hypercholesterolemia were significantly associated with increased MCI. Diabetes was significantly associated with AD in Asian and Pacific Islander (API) males and NHW females.

DISCUSSION: Targeted interventions aimed at curbing diabetes and hypertension onset for NHW and NHB males, and potentially reducing all comorbid conditions for NHW females may reduce MCI outcomes. Heterogeneity in the Hispanic and API diasporas should be considered when delineating comorbid conditions with MCI and/or AD.

HIGHLIGHTS: For non-Hispanic White (NHW) and non-Hispanic Black (NHB) males, diabetes and hypertension were associated with MCI. Diabetes, hypertension, and hypercholesterolemia were associated with mild cognitive impairment (MCI) for NHW females. Only hypertension was associated with MCI in NHB females. Diabetes was associated with Alzheimer’s disease (AD) in NHW females and Asian and Pacific Islander (API) males.

PMID:40916002 | DOI:10.1002/alz.70650

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Nevin Manimala Statistics

Insights Into the Separate and Joint Effects of Cadmium and Cesium on the Risk of Circadian Syndrome and the Underlying Mechanism: An Integrated Epidemiological and Network Toxicological Study

Biol Trace Elem Res. 2025 Sep 8. doi: 10.1007/s12011-025-04808-6. Online ahead of print.

ABSTRACT

The uncharted effects of cadmium and cesium on circadian syndrome (CircS), an emerging circadian rhythm disorder drawing considerable attention, and underlying mechanisms warrant exigent elaboration. Data of 11141 subjects from National Health and Nutrition Examination Survey 2005-2018 were incorporated to investigate separate-, joint-/interaction-, and mixture-effects of urinary cadmium and cesium on prevalent CircS risk exploiting survey weight regression and quantile g-computation. The underlying mechanisms were probed by network toxicological analysis. Separately, elevated cadmium or cesium was related to elevated (odds ratio = 1.32; 95% confidence interval: 1.15 ~ 1.52) or decreased (0.74; 0.58 ~ 0.94) CircS risk. Jointly, the effect of elevated cadmium on CircS was interactively (Pinteraction = 0.002) exacerbated by decreased cesium with participants with high-cadmium and low-cesium manifested the highest CircS risk (1.71; 1.27 ~ 2.34), and mixture of cadmium and cesium was related to elevated CircS risk (1.30; 1.21 ~ 1.40). Hypoxia-inducible factor-1 (HIF-1), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and mitogen-activated protein kinases (MAPK) signaling pathways were enriched and common (tumor necrosis factor [TNF], interleukin-6 [IL-6], tumor protein-53 [TP53]) and unique (HIF1A for cadmium, albumin [ALB] for cesium) targets were identified in linking cadmium and cesium with CircS. Separate exposure to cadmium or cesium was associated with increased or decreased CircS risk, while joint exposure to mixture of cadmium and cesium was interactively related to elevated CircS risk. Cadmium and cesium might affect CircS through mechanisms of modulating HIF-1, MAPK, and PI3K-Akt signaling pathways and shared (TNF, IL-6, and TP53) and unique (HIF1A for cadmium while ALB for cesium) targets.

PMID:40915987 | DOI:10.1007/s12011-025-04808-6

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Right ventricular myocardial blood flow estimated by 13N-ammonia positron emission tomography in patients with coronary artery disease

EJNMMI Rep. 2025 Sep 8;9(1):32. doi: 10.1186/s41824-025-00265-5.

ABSTRACT

BACKGROUND: Because the myocardium thickness and blood flow of the right ventricular (RV) are lower than those of the left ventricle, it is challenging to perceive the RV myocardium in normal individuals. This study aimed to measure the myocardial perfusion in the RV (myocardial blood flow [MBF]RV, myocardial flow reserve [MFR]RV) from 13N-ammonia PET images and investigate the associations between the MBFRV and MFRRV in patients with and without coronary artery disease (CAD) in the right coronary artery (RCA) region. A total 121 MBFRV and MFRRV were retrospectively measured from PET images by referring to the radioactivity and clinical blood flow values of the left ventricle. Adenosine-stressed and resting MBFRV and MFRRV were statistically compared among patients with RCA-MFR < 2.0 (group 1 [n = 61]), without RCA-MFR < 2.0 but with reduced MBF (group 2 [n = 16]), and without MFR < 2.0 (group 3 [n = 44]) using one-way analysis of variance with Tukey or Dunn post hoc analyses.

RESULTS: Stress MBFRV was lower in Group 1 than in Group 3, whereas resting MBFRV was higher in Group 1 than in Group 3. MFRRV gradually decreased from Group 3 to Group 1.

CONCLUSIONS: This study demonstrated the potential clinical applications of RV myocardial perfusion imaging using PET data. Our results highlight the importance of evaluating the MBFRV, particularly in patients with CAD. In CAD cases, the MFRRV was significantly reduced, with a more pronounced decrease, reflecting the severity of the disease. Additionally, increased resting MBFRV in patients with CAD may indicate compensatory mechanisms or microcirculatory disorders. These findings provide a foundation for further exploration of MBFRV and support the development of robust automated processing techniques to enhance clinical applicability.

PMID:40915986 | DOI:10.1186/s41824-025-00265-5

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3D Method for the Volumetric Evaluation and Visualisation of Dental Biofilms: A Proof-of-Principle Study

J Clin Periodontol. 2025 Sep 7. doi: 10.1111/jcpe.70019. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Traditional and planimetric plaque indices rely on plaque-disclosing agents and cannot quantify three-dimensional (3D) structures of dental biofilms. We introduce a novel computer-assisted method for evaluating and visualising plaque volume using intraoral scans (IOSs).

MATERIALS AND METHODS: This was a 4-day, non-brushing, plaque-regrowth study (n = 15). All plaque was removed at baseline (T0). IOSs at T0 and after 4 days (T4) were used for volumetric plaque assessment in six steps: model acquisition, model superimposition, computer-aided determination of tooth-surface margins, tooth-surface superimposition, visualisation and volumetric evaluation of biofilms. Plaque formation at T4 was additionally assessed with the Turesky Modification of the Quigley-Hein Plaque Index (TMQHPlI). We used Pearson’s correlation coefficients and multilevel models to investigate the relationships between TMQHPlI, volumetric plaque index (VPI) and the adjusted volumetric plaque index (AVPI, plaque volume/area).

RESULTS: VPI and AVPI positively correlated with the TMQHPlI, showing higher variability at lower TMQHPlI scores. VPI had a lower threshold for plaque detection and higher sensitivity than the TMQHPlI. VPI and TMQHPlI were highest on vestibular, maxillary and molar surfaces.

CONCLUSION: VPI quantifies biofilm deposits, is a more precise measure for plaque detection than the TMQHPlI and can be visualised using colour-coded maps displaying areas of equal plaque thickness.

PMID:40915977 | DOI:10.1111/jcpe.70019

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The Interplay Between Lifestyle and Oral/Faecal Microbial Profiles Among Periodontal Disease Patients: A Cross-Sectional Study

J Clin Periodontol. 2025 Sep 7. doi: 10.1111/jcpe.70029. Online ahead of print.

ABSTRACT

AIM: To characterise periodontal and faecal microbiomes of individuals with periodontal health (PH) and diseases, and evaluate associations with periodontal, sociodemographic, anthropometric, nutritional and lifestyle factors.

MATERIALS AND METHODS: Dental biofilm and faecal samples from individuals (n = 24/group) with PH, gingivitis (GG) and periodontitis (PE) were sequenced (16S rRNA). Anthropometric data and questionnaires on demographics, lifestyle, diet and intestinal habits were collected. Data were statistically analysed (p < 0.05).

RESULTS: GG and PE groups showed higher age, BMI, waist/abdominal circumferences and trans-fat intake and lower selenium and vitamin E intake compared to PH. Individuals with PE had higher hip circumference and lower income, education and intake of iron as well as vitamins A and B9. PE microbiomes (oral and faecal) showed distinct compositions, with the highest number of unique oral species. Faecal richness was lower in PE and GG compared to PH. Specific microbial taxa correlated with periodontal status and host factors.

CONCLUSION: Periodontal and faecal microbiomes vary across periodontal conditions. Discriminant analysis classified 77% of individuals by periodontal status, with key markers for PE including older age, poor dietary quality and distinct microbial oral and faecal signatures. These findings highlight the role of clinical, dietary and microbial factors in periodontal disease profiling.

PMID:40915974 | DOI:10.1111/jcpe.70029

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Mendelian Randomization Study: The Impact of Gut Microbiota on Survival in HR+ Breast Cancer Patients Under Different Treatment Regimens Through the Modulation of Immune Cell Phenotypes

Clin Breast Cancer. 2025 Aug 5:S1526-8209(25)00221-6. doi: 10.1016/j.clbc.2025.07.024. Online ahead of print.

ABSTRACT

BACKGROUND: Emerging evidence suggests that the gut microbiota (GM) may influence the progression of breast cancer by modulating immune responses. Given the vast diversity of GM and immune cell phenotypes, this study aimed to utilize the most advanced and comprehensive data to explore the causal relationships among the GM, immune cell phenotypes, and survival rates in hormone receptor-positive (HR+) breast cancer patients under different treatment regimens.

METHODS: We investigated the causal relationships between the GM, immune cell phenotypes, and survival rates in HR+ breast cancer patients treated with 11 distinct therapeutic strategies using Mendelian randomization. Inverse variance weighted analysis served as the primary statistical method. Additionally, we explored whether immune cell phenotypes act as mediators in the pathway from the GM to HR+ breast cancer survival rates.

RESULTS: In this comprehensive study, we identified 116 distinct GM species that established causal links with survival rates across 11 different subgroups of HR+ breast cancer patients. Furthermore, we discovered 13 potential pathways through which the GM might influence immune cell phenotypes, thereby affecting patient survival rates.

CONCLUSION: The GM is causally associated with survival rates in HR+ breast cancer patients treated with 11 different therapeutic strategies, and immune cell phenotypes serve as mediators in the pathway from the GM to HR+ breast cancer survival rates.

PMID:40915962 | DOI:10.1016/j.clbc.2025.07.024