Category: Statistics

Ann Work Expo Health. 2026 May 12;70(4):wxag036. doi: 10.1093/annweh/wxag036.

ABSTRACT

INTRODUCTION: The cohort of chrysotile cohort workers from Quebec was established in the 1960s. It remains one of the most influential investigations into health risk of chrysotile asbestos. The cohort principally relies on measurements of asbestos-containing dust via impingers (as million particles per cubic foot of inhaled air, mpcf) for exposure assessment, though counts of fibers (fibers per cubic centimeter of inhaled air, longer than 5 µm with aspect ratio greater than 3:1 f/cm3) are more toxicologically relevant.

OBJECTIVE: To develop an empirical model that predicts exposure to fibers as a function of dust levels and workplace in chrysotile asbestos mining operations in Quebec. The model is intended to be used in re-analysis of epidemiologic data that accounts for measurement error in exposure.

METHODS: We obtained a copy of 623 individual parallel measurements of dust and fibers collected in Quebec in the 1970s and their contextual information. We fitted mixed-effects linear models that predict fiber concentrations as a function of the counts of dust particles, with random effect of sampling site. To evaluate the general model performance, we conducted a 10-fold cross-validation.

RESULTS: Fiber concentrations ranged from 0.06 to 307 f/cm3. Dust counts ranged from 0.04 to 9.12 mpcf. The average fiber-to-dust ratio of (f/cm3)/mpcf) was 12 (SD 16, median 7), ranging from 0.07 to 227. We estimated a positive association between logarithms of fiber and dust counts, which is not materially affected by adjustment for workplaces. The model with the logarithms of dust levels per se explained 24% of between-site variance and 12% of within-site variance in the logarithms of fiber concentrations. The average cross-validated R2 was 68%.

DISCUSSION: We confirmed observations that the ratio of fibers to dust counts of chrysotile asbestos is not constant but depends on a variety of work characteristics, including the number of dust particles. Our results are consistent with similar analyses conducted by others. However, we could not access all side-by-side impinger and fiber measurements that existed based on published reports, and available measurements do not cover all the times and workplaces where members of the cohort of Quebec millers and miners were exposed to chrysotile. Our models of exposure to fibers have a general form that adheres to multiplicative Berkson-type error. We cannot rule out the dependence of this error on risk of health outcomes.

CONCLUSION: We conclude that it is possible to calibrate impinger counts of dust to the fiber concentrations in the air for chrysotile asbestos mined and processed in Quebec in the 1970s and quantify the associated uncertainty.

PMID:42166758 | DOI:10.1093/annweh/wxag036

JMIR Res Protoc. 2026 May 21;15:e82436. doi: 10.2196/82436.

ABSTRACT

BACKGROUND: Branched-chain amino acids (BCAAs) are essential amino acids for protein metabolism. Preclinical research in mice suggested that BCAA intake relative to other amino acids, in the context of a high-carbohydrate diet, was associated with hyperphagia, obesity, and reduced lifespan. These effects were not attributed to BCAAs alone, nor did they manifest through canonical mechanistic target of rapamycin-insulin-like growth factor 1 pathways; rather, they resulted from indirect effects of other amino acids, notably tryptophan, on appetite. As population aging and obesity-related chronic diseases present significant public health challenges, understanding appetite regulation is critical. To date, no clinical trial has examined the effects of BCAAs on appetite regulation in older adults. On the basis of our preclinical results, we hypothesized that, compared to the control diet, a diet supplemented either with BCAA or with BCAAs and methionine would increase appetite and energy intake, whereas supplementation with BCAA and tryptophan would not increase appetite.

OBJECTIVE: We aimed to translate these preclinical findings to humans by examining the effects of BCAAs per se and in combination with tryptophan and methionine on appetite and other health measures in a cohort of older participants.

METHODS: This randomized controlled clinical trial recruited 110 adults (aged 65-80 y; BMI 20-35 kg/m2). Participants were randomly allocated to four 4-week intervention groups: (1) control (no supplementation), (2) BCAAs, (3) BCAAs+tryptophan, or (4) BCAAs+methionine. All participants received a controlled diet, with intervention groups additionally receiving amino acid supplements. The primary outcomes are appetite assessed via self-reports and fibroblast growth factor 21 levels (a marker of protein appetite), and energy intake quantified from dietary intake data. Secondary outcomes include body composition, cardiometabolic health, gut microbiota, blood biomarkers, sleep, and physical performance. Descriptive statistics will be used to summarize participant characteristics. Linear mixed models will assess intervention effects, with and without adjustment for relevant covariates. Diet-specific self-reported appetite and palatability scores will be analyzed using generalized additive mixed models.

RESULTS: The trial was registered on April 12, 2021. Recruitment commenced in April 2022 and was completed in November 2025, with 308 individuals screened and 100 completing the study. Data analyses are planned for completion by December 2026, with results expected to be published in 2027. Data cleaning and analysis are currently in progress and are expected to be completed by December 2026, with trial results expected to be published in 2027.

CONCLUSIONS: This study will clarify the effects of BCAAs, either alone or in combination with tryptophan or methionine, on appetite and related outcomes in an older population. The findings may inform nutritional strategies targeting appetite regulation and metabolic health to support healthy aging.

PMID:42166751 | DOI:10.2196/82436

Pain Med. 2026 May 21:pnag066. doi: 10.1093/pm/pnag066. Online ahead of print.

ABSTRACT

BACKGROUND: Intravenous (IV) lidocaine has emerged as a non-opioid alternative for chronic pain management. However, the safety profile of repeated, long-term administration, particularly regarding cumulative exposure and cardiovascular comorbidities, remains poorly defined.

OBJECTIVE: To identify risk factors for serious adverse outcomes (SAOs) following IV lidocaine infusion in chronic pain patients.

METHODS: A retrospective cohort study examined 1,093 patients treated with IV lidocaine at a hospital-based pain clinic in Israel (2014-2022), totaling 15,820 infusions. SAOs were defined as emergency department visits within 14 days of infusion. Multivariable logistic regression and Generalized Estimating Equations (GEE) were used to assess predictors, including cardiovascular disease, cerebrovascular accident (CVA) history, diabetes mellitus, and cumulative infusion count, to distinguish between true dose-frequency effects and artifacts of cumulative exposure time. A secondary analysis retained only events plausibly attributable to lidocaine based on its pharmacological profile.

RESULTS: Fifty-five patients (5.0%) experienced SAOs. Cumulative exposure exceeding 50 infusions was the strongest predictor of adverse outcomes (OR = 12.58, p < 0.001). A GEE model accounting for repeated measures revealed that the risk per individual infusion remained stable and did not increase with the infusion sequence number (OR = 1.00, p = 0.854). CVA history was initially significant but lost significance in the secondary analysis when restricted to plausibly lidocaine-related events (n = 30), suggesting the association reflected disease progression rather than treatment effect. Conversely, pre-existing cardiovascular disease emerged as a significant predictor only in the refined analysis (OR = 3.88, p = 0.008), consistent with lidocaine’s known cardiac electrophysiological effects.

CONCLUSIONS: IV lidocaine demonstrates a favorable safety profile with low SAO incidence. While the statistical probability of an event increases with total exposure time, the per-infusion risk remains stable across the treatment course suggesting an absence of cumulative physiological toxicity. Pre-existing cardiovascular disease, specifically ischemic heart disease and arrhythmias, remains a primary risk factor. These findings support the use of enhanced cardiac monitoring for patients with these specific cardiovascular comorbidities and periodic risk-benefit reassessments for high-utilization patients.

PMID:42166744 | DOI:10.1093/pm/pnag066

J Gerontol A Biol Sci Med Sci. 2026 May 21:glag131. doi: 10.1093/gerona/glag131. Online ahead of print.

ABSTRACT

BACKGROUND: Frailty, an age-related loss of the ability to withstand stressors, is commonly measured using health deficit indices, often using survey or questionnaire data. We aimed to develop an electronic frailty index (eFI) using electronic health record (EHR) data linkages in the UK Biobank and assess its association with mortality.

METHODS: We calculated an eFI using 43 deficits, each corresponding to phecodes mapped to the United Kingdom (UK) and international classification coding systems. We compared this eFI to a validated 49-item survey-based FI for the UK Biobank and assessed associations of the eFI with risk of all-cause mortality (follow-up ≤ 10.2 years) and mortality following a stressor (heart attack or stroke) using Cox proportional hazard models.

RESULTS: Mean eFI in this cohort (N = 208,982) was 0.058 (SD = 0.06) and was higher in females than males. A 10% higher baseline frailty was associated with higher risk of all-cause mortality (HR(95%CI)=2.00(1.93-2.07)), although the magnitude of this association decreased when adjusting for socioeconomic-related covariates (HR(95%CI)=1.44(1.38-1.51)). Associations were stronger in men than women. eFI predicted mortality following both heart attack and stroke (HR(95%CI)=1.59(1.25-2.04) and HR = 1.33(1.13-1.57), respectively).

CONCLUSIONS: This EHR-based eFI has robust associations with mortality, suggesting that it can be used as a valid measure of frailty in the UK Biobank and can potentially be applied to other datasets with EHR data.

PMID:42166742 | DOI:10.1093/gerona/glag131

Aging Cell. 2026 Jun;25(6):e70517. doi: 10.1111/acel.70517.

ABSTRACT

In this cross-sectional cohort we analyzed data from 4260 “health enthusiasts” who purchased at least one saliva-based DNA epigenetic test between 2020 and 2025 and completed detailed lifestyle and supplement questionnaires. A proprietary 9-CpG clock with a mean absolute error of 5.4 years served as the primary biomarker of biological age. High prevalence (71%) of supplement use in this cohort increased our power to study the effects of supplements compared to earlier studies that focused on the general population. We tested the association between 84 commonly used supplements and biological age measured as Age Residual. In our cross-sectional analysis, a commercially available, delayed-release calcium-alpha-ketoglutarate (dAKG) + vitamin supplement (“Rejuvant”) was associated with an average 1.8-year lower Age Residual. The difference remained significant in models adjusted for age, sex, smoking, health status and additional covariates. In contrast, participants who reported taking regular AKG showed a much smaller and statistically insignificant benefit. Among medications, there was a non-significant benefit of antihistamine use, although the analysis was sample-size limited. In a longitudinal subset, intake of coenzyme Q10 (CoQ10) and dAKG was associated with increased odds of a lower Age Residual, but the results were not significant after multivariate correction. In conclusion, this study underscores the utility of an inexpensive saliva-based epigenetic test for population-level aging research and the benefits of health enthusiast cohorts. It highlights AKG and CoQ10, among others, as promising supplements warranting further investigation. Limitations like healthy user and recruitment bias remain and will require future controlled trials to fully address.

PMID:42166733 | DOI:10.1111/acel.70517

Gerontologist. 2026 May 21:gnag111. doi: 10.1093/geront/gnag111. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: We tested the feasibility and preliminary effects of the Mindfulness Self-Compassionate Care (MASC) program for dementia caregivers’ stress triggered by the care recipients’ neuropsychiatric symptoms.

RESEARCH DESIGN AND METHODS: Single-blind Stage 1B pilot randomized (2:1) controlled trial compared 6 weeks of MASC (n = 45) with a time and dose-matched education control (n = 23; Healthy Living for Caregivers [HLC]). T-tests examined within and between-group differences.

RESULTS: Most feasibility benchmarks were met. Mechanistic targets of mindfulness (p < .001; d = .58), self-compassion (p =.04; d = .32), self-efficacy (p < .001, d=.58), and distress from neuropsychiatric symptoms (p=.04, d=.33) showed small to medium pre-post improvements in the MASC group. Mechanistic validity was established through significant correlations between change in stress and change in mindfulness (r =-.58, p <.001), compassion (r =-.43, p =.003), self-compassion (r =-.77, p = <.000), self-efficacy (r =-.50, p =.001), and distress from dementia related neuropsychiatric symptoms (r =.33, p =.03). Pre-post improvements in MASC were not statistically significantly different compared with HLC for stress (t (64) =-1.07, p= .29) or other outcomes.

DISCUSSION AND IMPLICATIONS: The current study demonstrated feasibility and mechanistic target engagement and validity for MASC. As expected in an underpowered feasibility trial, clinical outcomes did not improve more than control, but trends favored MASC. These findings support a fully powered Stage 2 trial to test the efficacy of MASC compared with HLC.

PMID:42166728 | DOI:10.1093/geront/gnag111

Am J Respir Crit Care Med. 2026 May 21:aamag253. doi: 10.1093/ajrccm/aamag253. Online ahead of print.

NO ABSTRACT

PMID:42166725 | DOI:10.1093/ajrccm/aamag253

Genetics. 2026 May 21:iyag132. doi: 10.1093/genetics/iyag132. Online ahead of print.

ABSTRACT

In many bacterial species, strong genetic structure is present, where individuals are clustered into genetically distinct groupings within the species. However, high rates of homologous recombination have also been observed in many of these species, high enough that simple models of evolution predict that such genetic structure should be eliminated. One proposed resolution to this contradiction is the presence of recurrent bursts of reproduction caused by rapid adaptation or microepidemics. We investigate this hypothesis using coalescent simulations of the simplest bursty reproduction model. Our simulations show that bursts of reproduction can indeed create genetic structure even when recombination is so frequent that all structure would be eliminated in the absence of bursts. This genetic structure is only possible when there is a burst of reproduction that is sufficiently large and recent in the population’s history. We describe the mechanism by which a burst creates genetic structure and analyze its distinctive effect on the patterns of diversity, focusing on the distribution of pairwise genetic distances and its relationship to the fraction of identical blocks along the genome. Interestingly, genetic structure from bursts of reproduction can appear among pairs of samples which do not share any genetic material by clonal descent, a feature which cannot be observed in populations whose structure is just a consequence of limited recombination. However, we find that for other statistics beyond the distribution of pairwise distances, the simplest model of bursty reproduction cannot entirely reproduce the distributions observed in nature.

PMID:42166720 | DOI:10.1093/genetics/iyag132

JMIR Med Educ. 2026 May 21;12:e85892. doi: 10.2196/85892.

ABSTRACT

BACKGROUND: Mobile learning (mLearning) is widely used in medical education. Previous research has focused on technology acceptance and intervention effectiveness, but rarely on their integration. Using realist evaluation, this study investigated the conditions under which mLearning is adopted and associated with learning-related outcomes in an authentic curricular setting.

OBJECTIVE: This study aimed to examine how learner context and engagement patterns shape mLearning use and outcomes, while secondarily contextualizing its association with examination performance.

METHODS: A quasi-experimental study was conducted among fifth-semester undergraduate medical students at a German medical school across 2 consecutive summer semesters (2023 and 2024). Students were offered a voluntary, app-based mLearning course in microbiology, delivered via the eSquirrel platform. The course comprised interactive tasks, incorporating elements of gamification and spaced-repetition features. Data sources included nonreactive in-app usage logs, baseline academic performance data, demographic information, and postsemester questionnaire responses. Usage profiles were derived using cluster analysis. Context-mechanism-outcome patterns were explored by relating app usage status to academic performance and survey responses.

RESULTS: Of the 245 eligible students, 220 (89.8%) participated in the study; 110 (50%) used the app. In 2024, app users (n=64, 58%) initially appeared to outperform nonusers (n=46, 42%) in the oral microbiology examination (mean grade 2.3, SD 1.1 vs 2.8, SD 1.3; t63,0=1.90; 1-sided P=.03). After adjustment, these differences were largely explained by baseline academic performance, with only limited evidence of an independent intervention effect. Cluster analysis of app users identified 3 engagement profiles: continuous low-intensity use (n=60, 54%), increased use before the examination (n=31, 28%), and use at the beginning of the semester (n=19, 17%). Cluster 2 reported the greatest enjoyment, satisfaction, perceived learning gains, and examination performance in microbiology.

CONCLUSIONS: Nonreactive in-app usage data provided valuable insights into student engagement. The effectiveness of mLearning was not universal. Examination-oriented use, associated with more strategic and self-regulated study behavior, was linked to more favorable learning outcomes. Future research needs to address equity concerns, as higher-performing students tended to benefit most, as well as explore adaptive, context-sensitive approaches to support diverse learners.

PMID:42166712 | DOI:10.2196/85892

Eur Heart J. 2026 May 21:ehag336. doi: 10.1093/eurheartj/ehag336. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Myocardial infarction (MI) stands as a prominent manifestation of cardiovascular events. Most of the regenerative effects of stem cell therapies for MI are paracrine. A clinically translatable strategy that harnesses regenerative secretome while enabling minimally invasive delivery is needed. This study evaluated Regenerative Encapsulated Secretome as Cardiac Acellular Therapy (RESCAT), a formulation composed of cardiac stromal cell-derived secretome encapsulated in microparticles and embedded within a hyaluronic acid hydrogel, delivered via intrapericardial injection in a porcine model of MI.

METHODS: MI was induced using minimally invasive techniques. RESCAT was administered through clinically feasible intrapericardial delivery. Cardiac structure and function were assessed longitudinally in vivo. After the endpoint, infarct size and cardiomyocyte cell-cycle activity were assessed with histology. Single-nucleus RNA sequencing was performed to characterize cardiomyocyte transcriptional states and identify molecular pathways associated with therapeutic response.

RESULTS: RESCAT-treated pigs showed improved cardiac function and reduced infarct size compared with control groups. Enhanced cardiomyocyte cell-cycle activity and alterations in cardiomyocyte functional state were also observed. Single-nucleus transcriptomic analysis identified an FN1-expressing cardiomyocyte subtype linked to the activation of the PI3K-Akt pathway, which plays a role in cell survival and growth.

CONCLUSIONS: Intrapericardial delivery of RESCAT promotes functional and structural cardiac recovery in a clinically relevant porcine MI model. These findings support a minimally invasive, off-the-shelf acellular therapeutic strategy that enhances endogenous repair mechanisms and provides a foundation for translational development in ischaemic heart disease.

PMID:42166700 | DOI:10.1093/eurheartj/ehag336