Tag: nevin manimala

JAMA Netw Open. 2026 May 1;9(5):e2613292. doi: 10.1001/jamanetworkopen.2026.13292.

ABSTRACT

IMPORTANCE: Electronic cigarettes (EC) have been shown to expose users to fewer tobacco-related toxicants compared with combustible cigarettes. The current generation of ECs has rapidly shifted toward pod-based nicotine salt formulation ECs, and more research is needed to understand the impacts of using these EC products among those who smoke.

OBJECTIVE: To determine the short-term effects of switching from cigarettes to a pod-based 5% nicotine EC, compared with a 0% nicotine EC.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, parallel-arm, randomized, placebo-controlled trial with follow-up at 6 weeks (randomized phase) and 10 weeks (postrandomized phase) was conducted at a single-site academic medical center in Pennsylvania from April 22, 2022, to December 12, 2023. Participants included adults who smoked more than 4 cigarettes per day (CPD) and expressed interest in switching completely to an EC. Data were analyzed from August 23, 2024, to December 1, 2025.

INTERVENTIONS: Participants were allocated 1:1 to the standardized research EC (SREC) with 5% nicotine or 0% nicotine for 6 weeks.

MAIN OUTCOMES AND MEASURES: The primary outcome was concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine corrected for creatinine level at 6 weeks. Secondary outcomes included exhaled carbon monoxide (CO), cotinine level, CPD, CO-verified cigarette abstinence, and levels of volatile organic compounds.

RESULTS: A total of 104 participants (52 per group) were randomized, of whom 68 (65.4%) were female, with a mean (SD) age of 50.9 (10.0) years. At 6 weeks, the 5% SREC group did not have significantly lower NNAL levels (mean difference [MD], -116.6 [95% CI, -245.4 to 12.2] pg/mg; P = .08). However, a greater proportion of participants in the 5% SREC group were abstinent from cigarettes (19 of 52 [36.5%] vs 6 of 52 [11.5%]; P = .005), compared with the 0% SREC group. The 5% SREC group had greater cotinine levels (MD, 2367.8 [95% CI, 407.5-4328.2] ng/mg; P = .02); however, there were no differences in CPD (MD, -0.9 [95% CI, -3.9 to 2.1] CPD; P = .55) or exhaled CO levels (MD, -5.1 [95% CI, -12.9 to 2.6] ppm; P = .19) between groups. Levels of cyanoethyl mercapturic acid (CYMA) (MD, -49.0 [95% CI, -90.4 to -7.6] ng/mg; P = .02) and 3-hydroxypropyl mercapturic acid (3HPMA) (MD, -290.8 [95% CI, -514.0 to -67.6] ng/mg; P = .01), biomarkers of acrylonitrile (a carcinogen) and acrolein (a cardiac toxicant) exposure (both of which are respiratory toxicants), were lower in the 5% SREC group compared with the 0% SREC group.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of adults who smoke, switching from cigarettes to a 5% SREC vs a 0% SREC resulted in reduced exposure to some toxicants delivered by cigarette smoking and an increased rate of smoking cessation. ECs that deliver nicotine like a cigarette may have an important role in reducing the harmful toxicant exposure caused by cigarette smoking.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03625986.

PMID:42154468 | DOI:10.1001/jamanetworkopen.2026.13292

JAMA Netw Open. 2026 May 1;9(5):e2613399. doi: 10.1001/jamanetworkopen.2026.13399.

ABSTRACT

IMPORTANCE: Previous evidence suggests a bidirectional association between physical activity and cognitive function. It remains unclear whether long-term cognitive trajectories are associated with later differences in how older adults allocate time during the day between physical activity, sedentary behavior, and sleep.

OBJECTIVE: To assess whether long-term cognitive trajectories are associated with the subsequent amount of daily time in physical activity, sedentary behavior, and sleep.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included community-dwelling adults aged 50 years or older at baseline and residing in England, using cognitive data from waves 1 (2002 to 2003) to 9 (2018 to 2019) and accelerometer data from wave 10 (2021 to 2023) of the English Longitudinal Study of Ageing.

EXPOSURES: Participant-specific annual rate of change in episodic memory (assessed via immediate and delayed recall) and verbal fluency (assessed via animal naming), estimated using linear mixed-effects models.

MAIN OUTCOMES AND MEASURES: The movement behavior composition, comprising mean daily minutes of moderate to vigorous physical activity, light physical activity, sedentary behavior, and sleep time. Differences were estimated in time spent in each behavior between a less favorable memory or fluency trajectory (corresponding to the 25th percentile for participant-specific memory or fluency change), median trajectory (50th percentile), and a more favorable trajectory (75th percentile).

RESULTS: The study included 2529 participants (1394 [55.1%] female, 1135 [44.9%] male) with a mean (SD) baseline age of 56.1 (5.4) years. Compared with the less favorable memory trajectory, the more favorable trajectory was associated with 14 (95% CI, 8 to 21) more minutes of light physical activity and 12 (95% CI, -20 to -5) fewer minutes of sedentary behavior per day, with larger differences among participants older than 70 years (eg, 20 [95% CI, 11 to 30] more minutes light physical activity). Memory-related differences in moderate to vigorous physical activity and sleep were comparatively minor. Fluency showed similar patterns to memory, but time-use differences between trajectories were smaller.

CONCLUSIONS AND RELEVANCE: In this cohort study of older adults, participants with less favorable long-term memory trajectories were subsequently less active and more sedentary, suggesting that later-life activity patterns may partly reflect cognitive change.

PMID:42154466 | DOI:10.1001/jamanetworkopen.2026.13399

JAMA Netw Open. 2026 May 1;9(5):e2613616. doi: 10.1001/jamanetworkopen.2026.13616.

ABSTRACT

IMPORTANCE: Geographic variation in amputations following diabetic lower-extremity (DLE) wounds is substantial. Understanding the sociodemographic and health care factors associated with variations can inform policy to reduce amputations.

OBJECTIVE: To examine associations of regional patient and health care system characteristics with major amputations following DLE wounds.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted among Medicare fee-for-service beneficiaries aged 66 years and older with DLE wounds from 2017 to 2019. Data were aggregated at the hospital referral region (HRR) level. Analyses were performed between February 2025 and February 2026.

EXPOSURE: Diagnosis of a DLE wound.

MAIN OUTCOME AND MEASURES: The outcome was the HRR-year proportion of DLE wounds undergoing major amputation within 12 months after diagnosis. Key measures included HRR-year percentages of Black and Hispanic Medicare beneficiaries with DLE wounds, an economic deprivation index, clinician supply per 10 000 Medicare beneficiaries (primary care, endocrinology, podiatry, and revascularization-performing specialists), and the percentage of hospitals with wound management programs. Spatial-temporal bayesian models estimated associations of HRR-year amputations with these measures and were reported as odds ratios (ORs) with 95% credible intervals (CrIs).

RESULTS: The study cohort included 707 971 Medicare DLE wounds (median [range] age, 76 [65-11]; median [range] sex, 55.0% [44.0%-68.0%] male) in 306 HRRs with wide variation in median (range) racial composition (5.2% [0.0%-53.1% Black and 1.4% [0.0%-87.0%] Hispanic), economic deprivation index (60.6 [7.2-87.8]), specialist supply per 10 000 Medicare beneficiaries (podiatry: 4.0 [1.1-16.3]; endocrinology: 1.4 [0.2-5.4]; revascularization-performing specialties: 8.0 [3.9-28.0]) and the percentage of hospitals with wound management programs (63.4% [25.0%-100%]). The median (range) HRR-year proportion of DLE wounds followed by major amputation was 3.0% (0.3%-9.3%). In bayesian models, the percentages of Black (OR, 5.19; 95% CrI, 3.78-7.12) and Hispanic patients (OR, 2.39; 95% CrI, 1.73-3.29) and economic deprivation (OR, 1.29; 95% CrI, 1.02-1.62) had positive associations with amputations. Among health care factors, only HRR-level podiatrist supply had a negative association with amputations (OR, 0.74; 95% CrI, 0.66-0.82), corresponding to an estimated 19.1%, 6.6%, and 3.2% reduction in amputation odds with 1 additional podiatrist per 10 000 Medicare beneficiaries in low-, medium-, and higher-supply markets (approximately 1, 4, and 9 podiatrists per 10 000 beneficiaries).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of Medicare beneficiaries with DLE wounds, beyond social determinants of health, higher podiatrist supply was associated with fewer amputations. These findings suggest that increasing access to podiatry may reduce amputations among patients with DLE wounds.

PMID:42154463 | DOI:10.1001/jamanetworkopen.2026.13616

Clin Rheumatol. 2026 May 19. doi: 10.1007/s10067-026-08159-y. Online ahead of print.

ABSTRACT

PURPOSE: The primary objectives of this study were: (1) to describe the clinical characteristics and disease burden in a cohort of patients with SAPHO syndrome; (2) to evaluate the impact of SAPHO syndrome on quality of life using DLQI and HAQ; and (3) to identify independent risk factors associated with impaired quality of life.

METHODS: We retrospectively analyzed clinical data from 225 SAPHO patients at two tertiary hospitals using Dermatology Life Quality Index (DLQI) and Health Assessment Questionnaire (HAQ) scores. Correlation and regression analyses identified factors influencing QoL and physical function.

RESULTS: There was no significant correlation between bone pain location and total HAQ scores (P = 0.264); skin lesion types showed a significant correlation with DLQI scores (P = 0.039), and PPP was the main factor leading to impaired skin-specific quality of life.Patients were predominantly female (65.3%; mean onset age 35 ± 13 years). Palmoplantar pustulosis (92.9%) and sternoclavicular joint involvement (59.6%) were predominant. There is a statistically significant association between treatment type and DLQI score (P = 0.028), with a significant correlation with HAQ score (P = 0.05).Median DLQI was 17 (78.5% moderate-severe) and HAQ 0.12. Alcohol and education correlated with DLQI (P < 0.05), with education as an independent factor (P = 0.002). Duration and alcohol correlated with HAQ (P < 0.05), with alcohol as an independent factor (P = 0.036).

CONCLUSION: SAPHO significantly impacts patients’ quality of life, worsened by modifiable factors like alcohol and education; targeted interventions may improve prognosis.

PMID:42154424 | DOI:10.1007/s10067-026-08159-y

Ir J Med Sci. 2026 May 19. doi: 10.1007/s11845-026-04450-8. Online ahead of print.

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is frequently associated with neurological manifestations, most notably anosmia, raising questions regarding central nervous system involvement. Neuropathological studies have reported heterogeneous findings, and the relative contribution of direct viral neurotropism versus indirect systemic mechanisms remains controversial.

METHODS: An autopsy-based case-control study was conducted including 16 COVID-19-positive decedents and 15 age- and sex-matched COVID-19-negative controls. Histopathological examination focused on the olfactory bulb, olfactory tract, and frontal cortex. Reactive gliosis, microglial activation, perivascular inflammation, microvascular injury, neuronal eosinophilia, and corpora amylacea were assessed using standardized semiquantitative criteria and compared between groups.

RESULTS: COVID-19-positive cases demonstrated significantly increased reactive gliosis and microglial activation in the olfactory bulb, along with a higher frequency of mild perivascular lymphocytic infiltration in the frontal cortex. In contrast, corpora amylacea and petechial hemorrhages were observed in both COVID-19-positive and control groups, without statistically significant differences. No evidence of viral cytopathic changes or diffuse encephalitis was identified. Systemic pathological findings in COVID-19-positive cases were consistent with severe multisystem disease.

CONCLUSIONS: COVID-19 is associated with region-specific but non-uniform neuropathological alterations dominated by reactive and vascular changes rather than encephalitic processes. The inclusion of a contemporaneous control group demonstrates that several commonly reported histological findings represent nonspecific background changes. These findings support predominantly reactive and vascular mechanisms of CNS involvement in COVID-19 rather than direct encephalitic processes.

PMID:42154414 | DOI:10.1007/s11845-026-04450-8

Bull Math Biol. 2026 May 19;88(6):88. doi: 10.1007/s11538-026-01649-9.

ABSTRACT

Measurement error is an unavoidable feature of experimental data collection. It is common in mathematical biology to consider measurement error in the dependent variable. However, less attention has been given to errors in the independent variable. This work is focussed on the effects of independent variable measurement error in the biological sciences and the available statistical methods to account for these errors when performing parameter inference. Through a series of synthetic data studies, the effects of various error models are investigated, with a particular focus given to error in the time a measurement is taken. Across many scenarios, parameter inference proves robust to these errors, even without directly accounting for them. However, we find some systems, such as oscillating systems, are particularly susceptible to these errors and parameter estimates become biased. To aid researchers in the biological sciences, we review some statistical methods to correct for measurement error. We assess the applicability of these methods in a biological context by considering data availability and necessary assumptions for the methods. We find measurement error can have non-trivial and counter-intuitive effects on parameter inference and suggest assessing the available data should be an integral step in the modelling workflow. This allows researchers to identify when the integration of statistical methods to correct for measurement error are warranted.

PMID:42154409 | DOI:10.1007/s11538-026-01649-9

Sleep Breath. 2026 May 19;30(3):165. doi: 10.1007/s11325-026-03713-z.

ABSTRACT

BACKGROUND: Sleep disorders present a substantial challenge to public health. This study aims to analyze patterns in self-reported trouble sleeping, duration of sleep, and the utilization of prescription medications commonly used for insomnia (MCUFI) among the adult in the US.

METHODS: Data from five cycles of cross-sectional studies were gathered via the National Health and Nutrition Examination Survey (NHANES) spanning the years 2009 to 2010 through 2017 to 2018. Participants were asked to self-report on their trouble sleeping and sleep duration.

RESULTS: The prevalence of self-reported trouble sleeping rose noticeably from 24.93% (95% confidence interval [CI],22.73%-27.28%) in 2009-2010 to 30.03% (95%CI, 27.22%-33.00%) in 2017-2018 (P for trend = 0.001). In 2017-2018, 24.25% (95%CI, 22.04%-26.60%) reported < 7 h of sleep, which is a decreased of 11.94% since 2009-2010, while those reported ≥ 9 h increased from 7.14% (95%CI, 6.21%-8.20%) to 20.89% (95%CI, 19.90%-21.92%). However, those who slept for 7-9 h did not experience a significant change. Moreover, a U-shaped relationship was observed between sleep duration and trouble sleeping, indicating that the optimal amount of sleep for adults is 7.5 h. Furthermore, 3.72% (95%CI, 3.39%-4.09%) of adults used a MCUFI, with the most commonly used medications being zolpidem and trazodone. The overall MCUFI use did not change from 2009 to 2018 (P for trend = 0.9923).

CONCLUSION: In conclusion, the prevalence of self-reported trouble sleeping has risen in the US during the past decade, whereas the utilization of MCUFI has remained steady. Evidence from this study has shown that a sleep duration of 7.5 h is the optimal time for sleep with the lowest risk of encountering trouble sleeping.

PMID:42154404 | DOI:10.1007/s11325-026-03713-z

Mol Divers. 2026 May 19. doi: 10.1007/s11030-026-11589-0. Online ahead of print.

ABSTRACT

Developmental toxicity induced by environmental pollutants, particularly antibiotics, is often insidious and underestimated due to bioaccumulation and subsequent oral intake. This study developed a machine learning-based predictive strategy by constructing and comparing four models using Morgan fingerprints on a curated dataset of developmental toxicants. The optimal random forest model achieved an area under the receiver operating characteristic curve (AUC) of 0.87 (95% confidence interval: 0.83-0.91), an accuracy of 0.80, and a Matthews correlation coefficient of 0.59. Applying the ensemble model to 2,341 antibiotics identified miconazole as the highest-probability candidate (average probability 0.97). In zebrafish embryo toxicity assays, exposure to miconazole at low concentrations (0.3 and 3.0 µM) did not result in statistically significant mortality up to 72 h post-fertilization, whereas the high concentration (30 µM) caused significantly elevated mortality at 48 and 72 h (p < 0.05 compared to control). Network toxicology and molecular docking revealed that miconazole may interact with key targets AKT1 and BRAF, potentially perturbing the chemical carcinogenesis-reactive oxygen species signaling pathway. These integrated findings indicate that miconazole exhibits potential developmental toxicity, warranting further mechanistic and long-term exposure studies before drawing definitive regulatory conclusions.

PMID:42154399 | DOI:10.1007/s11030-026-11589-0

Eur J Health Econ. 2026 May 19. doi: 10.1007/s10198-026-01936-1. Online ahead of print.

ABSTRACT

Patient selection remains a major challenge in evaluating hospital performance. We exploit the quasi-random assignment of patients to hospitals, based on a rotation schedule between hospitals in the Upper Austrian capital of Linz. In an instrumental variable (IV) framework, we use high-quality administrative data and estimate hospital performance with respect to in-hospital mortality, 30-day mortality, and 30-day readmission. We contrast these results with those of traditional risk adjustment models based on patient observables. We find that the assessment of hospital performance is sensitive to the inclusion of patient observables and that increasing the number of socio-economic covariates to better control for patient risk profiles does not always help bring risk-adjusted estimates closer to IV estimates. The divergence between methods is most pronounced for readmissions, where risk-adjustment models imply large and statistically significant differences between hospitals, whereas IV estimates are substantially smaller and not statistically significant. Our results suggest that common risk adjustment does not adequately control for patient differences between hospitals and that hospital quality indicators based on common administrative data should be interpreted with caution. The trend toward personalized medicine may support the process of collecting more clinical information at the individual level, thus allowing for better quality comparisons between hospitals.

PMID:42154359 | DOI:10.1007/s10198-026-01936-1

Hernia. 2026 May 19;30(1):221. doi: 10.1007/s10029-026-03700-z.

ABSTRACT

BACKGROUND: The objective of this Systematic Review and Meta-Analysis (SR/MA) was to identify the best suture technique (short or large bites) for abdominal wall closure with respect to relevant outcome parameters such as incisional hernia (IH), surgical site infection (SSI) and linea alba (aponeurotic layer of the abdominal wall) dehiscence (LAD).

METHODS: Registration was done in PROSPERO, a systematic literature search was performed in three data bases (PubMed, Embase and Cochrane). Randomised controlled (RCT) as well as non-randomised controlled trials (n-RCT) comparing the short (SB) versus large bite (LB) technique for abdominal wall closure after midline laparotomy were eligible for inclusion. Quality assessment was performed for RCTs (ROB) & n-RCTs (ROBINS-1, MINORS). The incidence of IH, SSI, LAD as well as the length of hospital stay (LOS) and time to close the linea alba (aponeurotic layer of the abdominal wall) were analysed as outcome parameters. Odds ratio with 95% confidence intervals were chosen to determine statistical significance. Heterogeneity was explored using the I²-statistics and funnel plots evaluated a possible publication bias.

RESULTS: This SR/MA comprised in total 5886 patients (large bite group 3339 vs. 2547 short bite group) enrolled in 7 RCTs and 5 n-RCTs. The SB-technique was associated with a significant lower IH, SSI, FD rate and a shorter LOS compared to the LB-technique (IH: Odds Ratio OR = 0.47 (95% CI 0.38-0.58; p < 0.00001; I² = 11%)); SSI: OR = 0.53 (95% CI 0.42-0.67; p < 0.00001; I² = 0%); FD: OR = 0.60 (95% CI 0.38-0.93; p = 0.02; I² = 0%); LOS: Mean difference in days MD = -1.04 (95% CI -1.70, -0.37; p = 0.002; I² = 13%), respectively). Furthermore, pooled effect estimates derived from RCTs were comparable to n-RCTs. No statistical relevant publication bias was detected, and the confidence of resulting evidence was high according to the validated GRADE tool.

CONCLUSION: This systematic review and meta-analysis demonstrate consistent reductions in incisional hernia and surgical site infection with the small bites technique for midline laparotomy closure. The direction of effect is stable across randomized and comparative studies and supported by available long-term data. The clinical relevance and consistency of these findings support preferential use of the small bites technique in routine practice. The present evidence provides a robust basis for consideration in future updates of EHS abdominal wall closure guidelines.

REGISTRATION: PROSPERO, registration number: CRD420251033244, registration date: 16th April 2025.

PMID:42154339 | DOI:10.1007/s10029-026-03700-z