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Nevin Manimala Statistics

Covariate adjustment in LGBTQ+ health disparities research: aligning methods with assumptions

Am J Epidemiol. 2025 Sep 8:kwaf197. doi: 10.1093/aje/kwaf197. Online ahead of print.

ABSTRACT

In 2016, the NIH designated LGBTQ+ individuals (ie, lesbian, gay, bisexual, transgender, queer, and all sexual and gender minorities) as a health disparities population. The growing interest in studying the health of LGBTQ+ populations merits revisiting the methodological approaches researchers employ. We elucidate how researchers can identify appropriate adjustment sets for causal questions using directed acyclic graphs (DAGs). To illustrate these points, we simulated a simplified example using pregnancy loss as the outcome wherein we generate 1000 datasets with a sample size of 10 000 individuals. We motivate why covariates that are commonly used in LGBTQ+ health disparities research (eg, use of medically assisted reproduction) are mediators, not confounders, and how adjusting for these variables in causal research can induce bias by blocking part of the indirect effect of exposure on the outcome. Next, we illustrate the complexity of mediation analyses with social exposures due to mediator-outcome confounding induced by exposure and compare potential approaches. Then we demonstrate how collider stratification bias can arise from our sample recruitment and selection. Finally, we demonstrate how incorporating heterosexism (ie, stigma and discrimination) as an unobserved node in our DAG can guide decision-making on appropriate adjustment sets.

PMID:40916718 | DOI:10.1093/aje/kwaf197

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Nevin Manimala Statistics

Multi-Center Health Informatics to Examine the Implementation of Guideline-Directed Medical Therapy in Chronic Kidney Disease

J Prim Care Community Health. 2025 Jan-Dec;16:21501319251365314. doi: 10.1177/21501319251365314. Epub 2025 Sep 8.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) management was largely centered around renin-angiotensin-aldosterone system inhibitors (RAASi) optimization, until recent emergence of novel therapeutics. However, slow adoption of guideline-directed therapy leaves patients vulnerable to disease progression. In 2022, a data-driven informatics approach was introduced to track real-time adherence to best practices.

METHODS: This multi-center, ambidirectional cohort study analyzed data from a shared electronic health record system in a public healthcare cluster in Singapore, comprising 7 primary care institutions and 3 tertiary care hospitals. Patients aged ≥21 with CKD, managed between 1st March 2022 and 31st March 2024, were included. Prescription trends for RAASi, sodium-glucose co-transporter-2 inhibitors (SGLT2i), non-steroidal mineraloreceptor antagonists, and statins were examined, alongside albuminuria monitoring and comprehensive care uptake.

RESULTS: Among 34 217 patients, mean age was 72 ± 12 years; 57% received RAASi, 21% SGLT2i, and 66% statins. Among those meeting therapeutic indications, RAASi uptake remained stable at 74%, with 40% receiving ceiling doses. SGLT2i uptake doubled but remained below 40%, with lower adoption in non-diabetic and non-obese patients. Only 21% of albuminuric CKD G1-3b patients received optimal combination therapy with RAASi, SGLT2i, and statins despite only 4% hyperkalemia prevalence and 2% with systolic BP <110 mmHg. Among albuminuric CKD G3 patients with 5-year end-stage kidney disease risk ≥15%, 28% received optimal therapy. One-third lacked albuminuria monitoring and were less likely to receive comprehensive therapy.

CONCLUSIONS: Gaps persist in CKD care, particularly among non-diabetic, non-obese patients, and those without albuminuria monitoring. Health informatics-driven interventions can facilitate real-time process evaluation and adherence to best practices amid evolving treatment landscapes.

PMID:40916713 | DOI:10.1177/21501319251365314

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Nevin Manimala Statistics

CD63 is a diagnostic marker of prostate cancer and a prognostic marker of biochemical progression following radical prostatectomy

Histol Histopathol. 2025 Sep 8:18981. doi: 10.14670/HH-18-981. Online ahead of print.

ABSTRACT

AIMS: We aimed to analyze CD63, a cell surface protein that has been associated with tumor aggressiveness in several cancers, including breast, colorectal, and lung cancer, as well as melanoma, in prostate cancer.

METHODS: CD63 expression was analyzed immunohistochemically in a cohort of primary prostate cancers from 281 patients. The results were correlated with clinico-pathologic parameters, including biochemical recurrence. In addition, CD63 expression in 251 of the 281 patients with prostate cancer was compared with CD63 expression in matched benign tissue samples (490 tissue samples). The analysis was performed automatically using the open-source software QuPath© and tested for statistical significance. For comparison with the diagnostic markers AMACR and GOLPH2, CD63 was analyzed in an additional cohort of 198 Prostate cancers.

RESULTS: CD63 expression was found in 100% of prostate cancer cases and benign tissue spots. Increased CD63 expression was significantly associated with higher tumor stage (pT), tumor grade (ISUP), as well as shorter progression-free survival (PFS). Compared with the CD63 intensity of benign tissue, expression in tumor tissue was higher in >80% of cases. In addition, combining the expression of CD63 and AMACR, positivity reached 97.2%, making CD63 a promising diagnostic biomarker in challenging cases.

CONCLUSIONS: CD63 is commonly overexpressed in prostate cancer, and higher levels are associated with earlier biochemical tumor progression; hence, CD63 is a promising diagnostic and prognostic biomarker in primary prostate cancer.

PMID:40916710 | DOI:10.14670/HH-18-981

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Nevin Manimala Statistics

Sleep Quality in Chronic Pain Patients With and Without Strong Opioid Use: An Observational Study Using a Wearable Device

Neuropsychopharmacol Rep. 2025 Sep;45(3):e70052. doi: 10.1002/npr2.70052.

ABSTRACT

BACKGROUND: Although opioid analgesics may influence sleep in patients with chronic pain, the association between strong opioid use and sleep characteristics remains unclear. This study aimed to explore differences in sleep status among chronic pain patients with varying levels of opioid use.

METHODS: A total of 29 patients with chronic non-cancer pain who had been under treatment for more than 6 months were included. Patients were divided into four groups based on their opioid use: non-opioid users (n = 11), weak opioid users (n = 8), and strong opioid users receiving either < 60 mg/day (n = 5) or ≥ 60 mg/day (n = 5) in morphine-equivalent doses. Pain and psychological factors were assessed using the Numerical Rating Scale, Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, and Japanese Perceived Stress Scale. Subjective sleep status was assessed using the Athens Insomnia Scale. Objective sleep parameters, including total sleep duration, wakefulness after sleep onset (WASO), and sleep efficiency, were measured over seven nights using the wearable device. Sleep data were analyzed using a linear mixed-effects model with the opioid-naive group as the reference. Model 1 was unadjusted; Model 2 adjusted for age, sex, pain intensity, catastrophizing, anxiety, depression, and stress.

RESULTS: Patients in the ≥ 60 mg/day group showed shorter total sleep duration, longer WASO, and lower sleep efficiency in Model 1 compared to non-opioid users. These trends remained in Model 2, although statistical significance decreased. In contrast, those receiving < 60 mg/day showed trends toward shorter WASO and higher sleep efficiency. Subjective insomnia symptoms were more frequent in both strong opioid groups, especially in the high-dose group.

CONCLUSION: Among patients with chronic non-cancer pain, high-dose strong opioid use tended to be associated with poorer sleep, while low-dose use was linked to more favorable sleep characteristics.

PMID:40916701 | DOI:10.1002/npr2.70052

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Nevin Manimala Statistics

Pacing to pink noise enhances gait recovery from a mechanical perturbation

J Exp Biol. 2025 Sep 8:jeb.250650. doi: 10.1242/jeb.250650. Online ahead of print.

ABSTRACT

Effective locomotion requires physiological systems to adapt to instabilities. While gait perturbation recovery often appears rapid, it is possible that longer-lasting effects may be present. Therefore, this study explored recovery trends of gait dynamics following an experimenter-induced perturbation. Further investigation pertained to how responses to perturbations are influenced by walking to differently correlated auditory pacing cues (white noise, pink noise, isochronous, no cues) that altered stride-to-stride variability. The recovery rate of the temporal gait dynamics was measured 20 minutes post-perturbation using an Interrupted Time Series Analysis, a statistical method that evaluates the impact of an intervention by comparing trends in the data before and after the intervention is introduced. Pink noise gait, though seemingly affected by the perturbation initially, exhibited the fastest recovery to pre-perturbation gait dynamics. Conversely, white noise gait, despite appearing less affected at first, failed to completely recover, indicating a lasting perturbation effect. Isochronous gait remained unresponsive; an inflexibility that hinders adaptability to varying situations. The proposed statistical method reveals pre- and post-perturbation differences in gait dynamics and recovery rates, highlighting that pink noise gait offers faster adaptability to unexpected perturbations without long-term changes in gait dynamics.

PMID:40916693 | DOI:10.1242/jeb.250650

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Nevin Manimala Statistics

Role of Local Factors on the Occurrence of Peri-Implantitis: A Cross-Sectional Analysis

Clin Oral Implants Res. 2025 Sep 8. doi: 10.1111/clr.70036. Online ahead of print.

ABSTRACT

OBJECTIVE: A cross-sectional study was made to evaluate the role of local factors, including surgical, implant, and prosthesis-related parameters, in the presence of peri-implantitis.

METHODS: Consecutive partially edentulous patients with ≥ 1 implant presenting peri-implantitis were included. Clinical and radiographic data were collected to characterize local factors. Overall, 28 site-specific variables were analyzed for peri-implantitis and non-peri-implantitis implants. Simple and multiple logistic regression analyses were performed to explore potential associations. The diagnostic accuracy of those variables that demonstrated statistical significance in the multiple logistic regression analysis was further tested.

RESULTS: In total, 100 patients with 452 implants met the inclusion criteria. Of these, 227 implants (50.2%) were diagnosed with peri-implantitis, while 225 (49.8%) did not present peri-implantitis. The multiple logistic regression analysis demonstrated statistical significance for the following factors: (1) medial implant position within the prosthesis (OR = 3.9) was more prone to develop peri-implantitis; (2) internal Morse taper implant connection was the least likely to develop peri-implantitis (OR = 0.43); (3) mesio-distally centered implants were less prone to exhibit peri-implantitis (OR = 0.46); (4) bucco-lingual centered implants were less prone to exhibit peri-implantitis (OR = 0.29); (5) implants positioned inside (≥ 2 mm) the bony housing were less prone to exhibit peri-implantitis (OR = 0.13); and (6) implants tilted 10°-30° (OR = 5.84) and ≥ 30° (OR = 7.43) were more prone to exhibit peri-implantitis. Moreover, a prediction model based on the aforementioned factors yielded a high level of accuracy.

CONCLUSIONS: Implant malpositioning is a critical factor associated with peri-implantitis.

PMID:40916656 | DOI:10.1111/clr.70036

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Nevin Manimala Statistics

Effects of Physical Activity on Medical Expenses among Individuals with Obesity in Korea: Insights from a Nationwide Study

J Obes Metab Syndr. 2025 Sep 8. doi: 10.7570/jomes250520. Online ahead of print.

ABSTRACT

BACKGROUND: Research on the relationship between physical activity and medical expenses among individuals with obesity has been sparse. This study investigates that association using nationwide data from Korea.

METHODS: We analyzed data from the National Sample Cohort of the Korean National Health Insurance Service, including 112,531 adults with obesity who underwent at least two health screenings within a 2-year interval between 2009 and 2015. Participants were categorized into four groups based on changes in their regular physical activity during 2 years: non-exercisers, quitters, starters, and maintainers. A two-part model was used to assess the average and excess annual medical expenses per person, including outpatient and hospitalization expenses.

RESULTS: Lower levels of physical activity correlated with an increase in both average and excess annual medical expenses per person (P for trend <0.001). Non-exercisers showed the highest average annual medical expenses per person, followed by quitters, starters, and maintainers. The most substantial increases in overall medical expenses were observed among quitters, followed by non-exercisers, starters, and maintainers. These associations were prominent in individuals aged ≥65 years and those with both type 2 diabetes mellitus and hypertension.

CONCLUSION: In this nationwide study of individuals with obesity, lower physical activity levels were associated with increased medical expenses. Consistently engaging in physical activity might significantly lower medical expenses, particularly among elderly people and individuals with comorbidities. These findings highlight the importance of promoting This is a PDF file of an article accepted, but it is not yet the definitive version of record. sustained physical activity as a strategy for managing healthcare costs among individuals with obesity.

PMID:40916607 | DOI:10.7570/jomes250520

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Nevin Manimala Statistics

Association between Relative Skeletal Muscle Mass and Metabolic Dysfunction-Associated Steatotic Liver Disease Development in a Community-Based Population

J Obes Metab Syndr. 2025 Sep 8. doi: 10.7570/jomes25009. Online ahead of print.

ABSTRACT

BACKGROUND: This study explores how relative skeletal muscle mass is associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and the remission of baseline MASLD in a community-based population cohort.

METHODS: The study included 1,544 participants with an average age of 58 years. All participants underwent baseline and follow-up assessments in 2015 or 2016. Appendicular skeletal muscle mass was measured using an automatic bioelectrical impedance analysis (BIA), and total skeletal muscle mass was calculated using the BIA equation. Relative skeletal muscle mass was evaluated in two ways: divided by weight and divided by visceral fat area (VFA). Liver fat content was assessed using ultrasonography, and the NAFLD fibrosis score was calculated to quantify the degree of liver fibrosis.

RESULTS: During a median follow-up of 2.1 years, each one-standard deviation increase in relative total skeletal muscle mass was associated with a decreased risk of MASLD incidence among males (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43 to 0.74, adjusted for weight; and HR, 0.23; 95% CI, 0.13 to 0.42, adjusted for VFA) and females (HR, 0.62; 95% CI, 0.47 to 0.83, adjusted for weight; and HR, 0.37; 95% CI, 0.19 to 0.70, adjusted for VFA). In both sexes, the increase in relative appendicular skeletal muscle mass was also associated with a reduced MASLD risk. We found statistically significant inverse associations between relative skeletal muscle mass and both liver fat content and liver fibrosis.

CONCLUSION: Low relative muscle mass is associated with an increased risk of MASLD incidence and persistence. Therefore, increasing skeletal muscle mass over time might aid in the prevention and management of MASLD.

PMID:40916605 | DOI:10.7570/jomes25009

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Towards a National Longitudinal Tracking Framework of Health Graduate Practice Locations

Aust J Rural Health. 2025 Oct;33(5):e70085. doi: 10.1111/ajr.70085.

ABSTRACT

AIMS: Workforce maldistribution is a challenge to the equitable provision of healthcare in Australia. This Commentary details how a multi-university, large-scale, and growing data asset is positioned to contribute strategically and operationally to addressing national workforce priorities.

CONTEXT: The Nursing and Allied Health Graduate Outcome Tracking (NAHGOT) study is a prospective longitudinal research project with a commitment to nationwide geographical coverage. NAHGOT links practice location data (the outcome) from the Australian Health Practitioner Regulation Agency (Ahpra) with university administrative records, such as admission and placement data (explanatory variables). NAHGOT also links external surveys and publicly available spatial data describing socio-economic conditions and access to services. There are seven universities formally part of the collaboration, with five others in the process of joining. NAHGOT has established a framework including project governance, data linkage and management protocols, and a central repository for de-identified data.

APPROACH: The background of NAHGOT, the benefits to the Rural Health Multidisciplinary Training program, current limitations and challenges, and the case for scale-up and future direction are described.

CONCLUSION: Universities are uniquely positioned to lead graduate tracking as they have access to a suite of key explanatory variables not available elsewhere. Increasing the number of participating universities within NAHGOT is a priority, as is broadening the pool of disciplines beyond those covered by Ahpra. The geo-enrichment of placement and practice data is also a priority. This will allow a more granular understanding of local workforce dynamics that can be overlooked if analysis is limited to existing geographical classifications.

PMID:40916591 | DOI:10.1111/ajr.70085

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Epidemiology and Genetic Surveillance of Human Hepatitis E Virus Infections in Shandong Province, Eastern China, 2019-2023

J Med Virol. 2025 Sep;97(9):e70595. doi: 10.1002/jmv.70595.

ABSTRACT

Hepatitis E virus (HEV) has emerged as a major agent of acute viral hepatitis, with zoonotic genotype 4 (HEV-4) representing a public health concern in China. In this study, we integrated province-wide enhanced hepatitis E surveillance data and molecular profiling from Shandong Province of eastern China, 2019-2023, with the aim of elucidating the epidemiology, genetic diversity, and clinical correlations of autochthonous HEV infections. In total, 5826 cases were reported during the study period, with 72.8% in males and 90.6% aged ≥ 40 years. 695 sequences were obtained from 553 males, 142 females, and an age range of 3-96 years (median 59 years). HEV-4d was predominant (84.0%), followed by 4b (9.9%), 4a (3.7%), and 4h (1.6%). Three HEV-3 strains and two imported HEV-1 strains were also identified. A high degree of nucleotide similarity was observed between dominant HEV-4d strains circulating in human populations and indigenous strains previously isolated from swine, cattle, and sheep within the province. Comparative analysis revealed no statistically association between the four principal HEV-4 subtypes and specific clinical manifestations, likely reflecting conserved pathogenic potential across these subtypes. Ongoing molecular surveillance is essential to monitor evolutionary trends and transmission dynamics of HEV within the framework of One Health.

PMID:40916566 | DOI:10.1002/jmv.70595