Nevin Manimala

JMIR Hum Factors. 2026 May 21;13:e60551. doi: 10.2196/60551.

ABSTRACT

BACKGROUND: Telemedicine has rapidly expanded; however, standardized, telemedicine-specific patient-reported experience measures tailored to outpatient workflows are limited in many settings.

OBJECTIVE: This study aimed to develop and psychometrically validate the Telemedicine Service Experience Questionnaire (TSEQ) for Chinese outpatients using telemedicine services.

METHODS: We conducted a web-based survey among outpatients who completed a telemedicine consultation at Peking Union Medical College Hospital between July 1, 2021, to August 31, 2021, and who had used telemedicine services, using an adapted Chinese Patient Experience Questionnaire that encompasses 15 questions across 4 dimensions, to investigate patients’ telemedicine consultation experiences. Item generation was informed by a literature review, workflow mapping, and expert review. We evaluated the factor structure using exploratory factor analysis and confirmatory factor analysis on the full sample with cross-validation. Reliability was assessed using Cronbach α and item-total correlations.

RESULTS: In total, 3338 participants completed the survey (mean age 45.3, SD 17.8 y; n=2182, 65.4% female participants; n=1827, 54.8% with college education or above). The exploratory factor analysis of the final 14-item scale resulted in 4 factors. After scrutinizing the content, these factors were labeled “Service Efficiency,” “Post-treatment,” “Information Guidance,” and “Humanistic Care,” and they demonstrated good internal consistency (Cronbach α values of 0.876, 0.840, 0.962, and 0.876, respectively). Moreover, as the average variance extracted values were greater than 0.5 and the composite reliability values were greater than 0.7, the TSEQ scale has high convergent validity. Our findings suggest that the psychometric properties of the 14-item TSEQ are valid and reliable for assessing telemedicine service experience among Chinese outpatients.

CONCLUSIONS: The TSEQ demonstrates a stable multidomain structure with satisfactory reliability and validity for evaluating outpatient telemedicine service experience in China. The instrument can support routine quality monitoring and guide targeted workflow improvements. Future studies should validate the TSEQ in multisite and postpandemic samples and examine measurement invariance across key subgroups.

PMID:42166784 | DOI:10.2196/60551

J Chem Inf Model. 2026 May 21. doi: 10.1021/acs.jcim.6c00481. Online ahead of print.

ABSTRACT

Nuclear magnetic resonance (NMR) structure determination is an important problem in education, industry, and research. Solving NMR spectra requires expert knowledge, critical thinking, and careful evaluation of multiple features of spectral data. This study explores the capabilities of large language models (LLMs) and large reasoning models (LRMs) for solving NMR spectral tasks. We selected 112 problems from NMR-Challenge.com, which has been used by students practicing NMR structure elucidation, collecting >1 million human responses, and developed a plain text problem format for evaluating LLM reasoning in this domain. We evaluated 10 LLMs (GPT-4o, GPT-4o-mini, o1, o1 mini, o3 mini, Claude-3.5 Sonnet, Gemini 2.0 Flash, Meta Llama 3, ChemDFM-R, and ether0), comparing 5 prompts to spur chain-of-thought reasoning in different ways, especially comparing the influence of providing background NMR chemistry knowledge, reasoning strategy, or both. Newer models trained to emphasize reasoning performed better, and increasing reasoning effort led to modest improvements, but prompting and varying temperature did not have an effect. We also evaluated undergraduate organic chemistry students in a controlled setting and analyzed answer submission statistics from global submissions to NMR-Challenge.com, to characterize human performance on these problems. The top-performing students surpassed smaller models like GPT-4o by 24%, 33%, and 29% on the Easy, Moderate, and Hard sets, respectively. However, reasoning models like o1 exceeded student performance by 13%, 14%, and 19%, respectively. Patterns in mistakes made by humans and LLMs reveal that errors made by LLMs are similar to those typically made by humans, for instance, incorrect positioning of substituents on benzene and incorrect orientation of carboxyl groups in esters. However, LLMs still “think” differently from humans, in some cases, providing answers that no human submitted via the website. This work also illustrates how NMR spectral problems can be used to benchmark LLMs on reasoning-heavy tasks in chemistry, though for this particular set of problems, early 2025 LLMs already exceed undergraduate student performance.

PMID:42166780 | DOI:10.1021/acs.jcim.6c00481

Health Rep. 2026 May 20;37(5):15-25. doi: 10.25318/82-003-x202600500002-eng.

ABSTRACT

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in Canada. Breast density substantially influences breast cancer risk and mammography performance. However, OncoSim-Breast, a Canadian microsimulation model representing breast cancer control, including cancer onset, screening, and survival, has not previously explicitly accounted for breast density. This study describes the incorporation of density-specific parameters into the OncoSim-Breast model.

DATA AND METHODS: Breast density-specific inputs were integrated into OncoSim-Breast using data from five Canadian provinces. Three key parameters – prevalence, relative risk of breast cancer, and digital mammography performance (sensitivity and specificity) – were estimated by age group and breast density category, following the American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) classification (categories A to D). Calibration experiments and internal validations were conducted to ensure the updated OncoSim-Breast model aligned with observed data from the Canadian Cancer Registry.

RESULTS: The prevalence of dense breasts declined with age: BI-RADS categories C and D accounted for 58% of women younger than 50 years and 26% of those aged 70 and older. Digital mammography sensitivity also decreased with increasing density: among women younger than 50 years, sensitivity was 88% for Category A and 69% for Category D. The updated OncoSim-Breast model accurately replicated age-specific incidence, age-adjusted incidence, and stage distribution based on historical data from the Canadian Cancer Registry (2010 to 2019).

INTERPRETATION: Incorporating breast density-specific parameters substantially improved the accuracy and policy relevance of OncoSim-Breast. The updated model provides a validated tool to inform screening policy decisions for Canadian women, allowing consideration for the effect of the variability of breast density among women.

PMID:42166779 | DOI:10.25318/82-003-x202600500002-eng

Health Rep. 2026 May 20;37(5):3-14. doi: 10.25318/82-003-x202600500001-eng.

ABSTRACT

BACKGROUND: Previous work has noted variability in cancer incidence and cancer-related outcomes according to place of residence. This study examined geographic variability in the incidence and mortality of breast cancer among females in Canada.

DATA AND METHODS: Data from the 2021 Canadian Cancer Registry (breast cancer incidence) and the Canadian Vital Statistics – Death database (breast cancer mortality) were examined across provinces and territories, community sizes, and peer groups (i.e., clusters of health regions with similar socioeconomic and demographic characteristics). Age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) per 100,000 females per year and their rate ratios were calculated, as well as age group-specific and age-standardized stage-specific incidence rates.

RESULTS: From 2010 to 2020, the invasive breast cancer ASIR was 140.1 per 100,000 females annually, with marked geographic and community variation. Mean age at diagnosis was 62.7 years, and it was lowest in northern and remote regions. Three-quarters of cases were stages I and II, though stage-specific ASIRs varied. Overall ASIRs were highest in peer groups B (urban centres with large immigrant and racialized populations) and D (rural regions in Quebec, Ontario and the Prairies). They were lowest in peer groups F (Northern and remote regions with young populations), G (Montréal, Toronto, and Vancouver), and H (urban centres in Ontario and British Columbia). From 2010 to 2022, the ASMR was 28.3 per 100,000, highest in rural Eastern Peer Group E and lowest in large urban centres.

INTERPRETATION: The study found significant variability in female breast cancer incidence and mortality across the geographical classifications considered, highlighting the need for a closer look at regional- and individual-level factors and their respective associations with cancer incidence and outcomes.

PMID:42166778 | DOI:10.25318/82-003-x202600500001-eng

JMIR Mhealth Uhealth. 2026 May 21;14:e87628. doi: 10.2196/87628.

ABSTRACT

BACKGROUND: Frailty is highly prevalent in survivors of multiple myeloma (MM) after autologous hematopoietic cell transplantation and is associated with poor functional recovery and adverse clinical outcomes. Although exercise is known to improve physical function, traditional center-based rehabilitation models are often inaccessible to this population during early posttransplant recovery. Mobile health (mHealth)-supported exercise may offer a scalable alternative; however, evidence in hematologic malignancies remains limited.

OBJECTIVE: This study aimed to evaluate the effects of a 16-week mHealth-supported exercise rehabilitation program on frailty phenotype and physical function in survivors of MM within 180 days after autologous hematopoietic cell transplantation.

METHODS: In this single-center randomized controlled trial, participants who self-reported as prefrail or frail were randomized 1:1 to an mHealth-supported exercise group (n=16) or usual care control (n=16). Remote assessments were conducted at baseline (week 0), midpoint (week 9), and follow-up (week 17). The intervention consisted of 8 weeks of supervised tele-exercise (3 sessions/week, 50 minutes/session), followed by 8 weeks of independent home-based exercise using the same mHealth platform. Exercise intensity was prescribed using a repetitions-in-reserve-based rating of perceived exertion approach with symptom-guided progression. The primary outcome was change in the 5-component Fried frailty phenotype score (0-5). Secondary outcomes included Short Physical Performance Battery components, chair stand time, gait speed, and handgrip strength. Intention-to-treat analyses were conducted using generalized estimating equations to evaluate between-group differences over time.

RESULTS: Participants had a mean age of 64.6 (SD 7.1) years and were enrolled a mean of 136 (SD 36.3) days posttransplant. At baseline, 94% (30/32) of participants were classified as frail. Adherence to the supervised sessions was 85% (326/384 sessions), and adherence during the unsupervised phase was 78% (298/384 sessions). The exercise group demonstrated a significantly greater reduction in frailty score compared with control from baseline to week 17 (P<.001). Between-group difference estimates showed a clinically meaningful improvement favoring exercise at both week 9 and week 17 (P<.001). Chair stand time improved significantly in the exercise group compared with control, with faster completion times observed at week 9 and sustained through week 17 (P=.002). Improvements in other Short Physical Performance Battery components and handgrip strength favored the exercise group but did not reach statistical significance. No serious adverse events occurred.

CONCLUSIONS: A 16-week mHealth-supported, progressively prescribed exercise rehabilitation program was feasible, safe, and effective in reversing frailty phenotype and improving functional mobility in survivors of MM early after autologous transplantation. This approach provides a scalable model for delivering structured rehabilitation during a high-risk recovery window. Larger trials incorporating attention-matched controls and longer follow-up are warranted.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05142371; https://clinicaltrials.gov/study/NCT05142371.

PMID:42166768 | DOI:10.2196/87628

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