Category: Statistics

J Med Internet Res. 2026 May 20;28:e69634. doi: 10.2196/69634.

ABSTRACT

BACKGROUND: Digital approaches to weight management have the potential to produce cost-effective and scalable weight management solutions. Effective behavior change interventions typically promote self-regulation of energy balance behaviors, which may be enhanced by incorporating emotion regulation strategies.

OBJECTIVE: This study aimed to evaluate the effectiveness of a digital behavior change toolkit for weight loss maintenance in European adults who had achieved ≥5% weight loss in the previous 12 months. We hypothesized that a combined intervention targeting self-regulation or motivation and emotion regulation would be more effective than either component alone, and that each would outperform an active control.

METHODS: The Navigating to a Healthier Weight (NoHoW) trial was a 2×2 factorial randomized, single-blind, controlled trial involving 1627 adults who had achieved ≥5% weight loss in the previous 12 months (initial BMI ≥25 kg/m2) across 3 European centers (the United Kingdom, Denmark, and Portugal). The trial evaluated a digital toolkit for weight management subsequent to an initial ≥5% weight loss in the prior 12 months. Participants were assigned using adaptive stratified sampling to one of four groups: (1) self-regulation or motivation (n=403), (2) emotion regulation (n=416), (3) combined motivation and emotion (n=408), or (4) active control (generic content, regular self-weighing, and Fitbit use, n=400). The primary outcome was weight change from baseline to 12 months. Prespecified secondary outcomes included cardiometabolic markers. Linear models adjusted for recruitment center, sex, age group, BMI group, and pretrial weight loss. Subgroup analyses were conducted by sex.

RESULTS: At 12 months, 76% (364/1627) of participants remained in the study. In the primary ITT analysis in all participants, none of the intervention arms (motivation, emotion, or combined) differed significantly from the active control for weight change at 12 months. Completer and per-protocol analyses produced similar patterns and did not change the overall interpretation. In the per-protocol sample, men regained 0.14 kg, and women regained 0.54 kg of their pretrial weight loss. Subgroup analyses indicated a small effect of the motivation intervention in men, but this was not clinically meaningful and did not alter the primary null findings. Nearly half of ITT participants regained weight, and no significant intervention effects were observed for cardiometabolic secondary outcomes.

CONCLUSIONS: The NoHoW trial was the first large-scale, multicountry 2×2 factorial randomized controlled trial to evaluate a digital-only toolkit based on self-regulation or motivation and emotion regulation techniques for weight loss maintenance. NoHoW found no evidence in the primary ITT analysis that digital interventions targeting self-regulation or emotion regulation improved weight loss maintenance compared with the active control. A small subgroup effect in men should be interpreted cautiously and does not change this conclusion. The trial provides evidence on both the limitations and potential of digital behavior change interventions for long-term weight outcomes. Future digital interventions may benefit from enhanced engagement and tailored content to improve long-term weight outcomes.

PMID:42160776 | DOI:10.2196/69634

JMIR Form Res. 2026 May 20;10:e83363. doi: 10.2196/83363.

ABSTRACT

BACKGROUND: The Technology Adoption Model (TAM) offers a potential framework for elucidating the relationships between data privacy or security concerns and behavioral intention, perceived usefulness (PU), and perceived ease of use (PEOU) of mobile health (mHealth) apps, particularly for patients’ self-care management. In Saudi Arabia, limited information is available on these pertinent research areas despite the government’s relentless efforts to bolster the use of mHealth apps.

OBJECTIVE: This study applies the TAM and the psychosociocultural framework to explore the influence of patients’ data privacy and security concerns on the PU, PEOU, and behavioral intention to use mHealth apps for self-care management in Saudi Arabia.

METHODS: A cross-sectional study was conducted by recruiting patients using mHealth apps for self-care from various provinces in Saudi Arabia. Research instruments were developed based on the components of 2 theories: the psychosociocultural framework and TAM, which were then piloted, validated, and distributed to participants via Google Forms. Linear regression models were performed to test the hypothesized relationships.

RESULTS: Overall, 567 patients using mHealth apps participated in the study. Slightly more than one-third (217/567, 38.2%; range 35.6%-41.4%) of the participants expressed a high level of concern regarding data privacy, confidentiality, and security, with significant predictors being female gender, higher educational qualifications, and younger age groups (<46 years). About 18% to 25% of the variance in PU, PEOU, and behavioral intention to use mHealth apps was explained by the tested factors. Patients were more likely to have higher PU following a unit decrease in data confidentiality (β=.31; P=.01) and security concerns (β=.47; P=.01). The PEOU of mHealth apps increased as users demonstrated less concern regarding data privacy (β=.18; P=.001), confidentiality (β=.24; P<.001), and security (β=.43; P=.02). Likewise, behavioral intention to use mHealth apps also increased significantly following a reduction in respondents’ concerns toward data privacy (β=.18; P=.02), confidentiality (β=.24; P=.03), and security issues (β=.36; P=.01).

CONCLUSIONS: Specific demographic factors and concerns regarding data security and privacy influence patients’ PU, PEOU, and behavioral intention to use mHealth apps for self-care management. Targeting the age-, education-, and gender-based differences regarding the usage of mHealth apps. Health care providers and policymakers may consider age-, education-, and gender-based differences when developing strategies to improve the adoption of mHealth apps among the Saudi patient population.

PMID:42160774 | DOI:10.2196/83363

Neurology. 2026 Jun 23;106(12):e218123. doi: 10.1212/WNL.0000000000218123. Epub 2026 May 20.

ABSTRACT

BACKGROUND AND OBJECTIVES: Smoking cessation is universally prioritized for the prevention of cardiovascular disease and cancer, but its impact on dementia risk remains uncertain. We aimed to evaluate the associations of smoking cessation and postcessation weight gain with long-term risk of dementia and cognitive trajectories.

METHODS: We conducted a prospective cohort study using data from the US Health and Retirement Study (1995-2020). A total of 32,802 dementia-free adults (mean age 60.5 years [SD 10.7]; 57.1% female) were included. Smoking status and body weight were assessed biennially through structured interviews. The primary outcome was incident dementia identified using the Langa-Weir algorithm, and the secondary outcome was cognitive function measured on a 27-point scale.

RESULTS: Over 25 years of follow-up (median 9.9 years, interquartile range 4.4-16.4 years), 5,868 dementia cases were documented. Compared with current smokers, individuals who quit during follow-up had a lower dementia risk after quitting (hazard ratio 0.84, 95% CI 0.73-0.95), similar to those who had quit before baseline (0.79, 0.72-0.87) and to never smokers (0.75, 0.69-0.83). The benefits of cessation were largely limited to participants with no or modest 2-year postcessation weight gain (≤5 kg). By contrast, the association of quitting accompanied by >10-kg weight gain was not statistically significant (1.33, 0.87-1.82). Restricted cubic spline analysis showed decreasing dementia risk with longer time since quitting, and the risk approached that of never smokers and plateaued at around 7 years after cessation. Cognitive trajectory analyses showed that quitting was associated with long-term slower cognitive decline (slope difference 0.19 points per decade, 95% CI 0.00-0.38) but no transient cognitive change (0.57; 95% CI -0.69 to 1.83), especially among those with minor weight gain (slope difference 0.23 per decade, 95% CI 0.03-0.43).

DISCUSSION: Smoking cessation was associated with a sustained lower dementia risk and slower cognitive decline, comparable to never smokers and those without short-term risk increase. However, postcessation weight gain may attenuate these advantages, highlighting the need for weight management in cessation programs. These findings should be interpreted cautiously, given the potential residual confounding and measurement error.

PMID:42160746 | DOI:10.1212/WNL.0000000000218123

Brief Bioinform. 2026 May 4;27(3):bbag245. doi: 10.1093/bib/bbag245.

ABSTRACT

Bioinformatics is entering a new phase characterized by the integration of universal biological models and multi-agent systems to enable end-to-end scientific discoveries. This review argues that the next paradigm shift will go beyond traditional predictive models and generative artificial intelligence (AI) toward agentic AI: systems capable of planning, acting through tools, reflecting on results, and iterating until a goal is achieved. We first examine recent foundational models that produce transferable representations across omic modalities, such as scGPT, Nicheformer, and EpiAgent, and discuss their architectural choices, training regimes, and interpretability constraints. We then analyze biomedical agent frameworks through their main components (planning, action, reflection, and memory), highlighting representative systems such as ClinicalAgent and Biomni that operationalize these ideas in controlled environments. Next, we focus on hypothesis validation mechanisms, including retrieval-augmented generation for evidence grounding, sequential statistical testing, and benchmarking methodologies designed to quantify robustness and reproducibility. Finally, we summarize emerging applications in drug discovery and personalized medicine, from molecular literature analysis and protocol automation to drug repurposing for rare diseases and closed-loop synthesis. We conclude by outlining the main challenges ahead, namely hallucinations, interpretability, systemic biases, integration with clinical infrastructures, and regulatory and ethical requirements, and propose a roadmap for the development of scientific agents that are not only high-performing but also reliable, verifiable, and implementable in real biomedical contexts.

PMID:42160738 | DOI:10.1093/bib/bbag245

Intern Med J. 2026 May 20. doi: 10.1111/imj.70482. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Metabolic (dysfunction)-associated steatotic liver disease (MASLD) has been linked to an increased risk of extrahepatic cancers. Whether MASLD or metabolic (dysfunction)-associated fatty liver disease (MAFLD) is associated with an increased risk of extrahepatic cancer incidence or death in Australia is unknown.

METHODS: This was a study from the Crossroads 1 cohort, enrolling randomly selected adults from regional Australia between 2001 and 2003 to partake in a comprehensive evaluation of health. MASLD is defined as fatty liver index (FLI) ≥60, one metabolic risk factor and no alternate liver disease, while MAFLD was defined as FLI ≥60 with overweight/obesity, type 2 diabetes mellitus (T2DM) and/or metabolic dysfunction. Longitudinal outcomes linked through cancer registry, hospital admission and death registry datasets and defined according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision codes.

RESULTS: In total, 1324 and 1444 participants respectively are included in the MASLD and MAFLD analyses. Prevalence was 35.4% (MASLD) and 40.7% (MAFLD). Median follow-up time was 19.7 years (interquartile range 19.1-20.1). Neither form of fatty liver disease (FLD) was associated with an increased risk of death related to extrahepatic cancer compared to those without FLD. Both forms of FLD were associated with an increased incidence of colorectal cancer (MASLD adjusted sub-hazard ratio (sHR) 2.90, 95% CI 1.17-7.17; MAFLD: sHR 3.15, 95% CI 1.43-6.96) following adjustment for confounding factors. This was primarily influenced by a difference seen among females (sHR 3.89-4.32).

CONCLUSION: Neither MASLD nor MAFLD was associated with an increased risk of extrahepatic cancer-related death, but they were associated with an increased risk of colorectal cancer incidence, particularly among females.

PMID:42160725 | DOI:10.1111/imj.70482

Traffic Inj Prev. 2026 May 20:1-17. doi: 10.1080/15389588.2026.2663051. Online ahead of print.

ABSTRACT

OBJECTIVE: The 50 year trends were determined for societal costs and injury HARM from motor vehicle crashes in the U.S. The injury and fatality HARM provides a basis to set priorities and for cost-benefit analyses in automotive safety. The over- and under-counting of injuries and deaths was analyzed, and the costs for injury fraud, malingering, victim psychology, and product liability were evaluated.

METHODS: NHTSA published eight studies since 1970 showing societal costs for motor vehicle crashes, including medical costs, property damage, productivity losses, insurance administration, losses to other individuals, employer losses, funeral costs, community service losses, pain and suffering, and miscellaneous accident costs. The trend in costs was determined for: (1) total societal costs, (2) injury HARM, (3) fatalities, (4) nonfatal injuries, (5) MAIS 4 + F, and (6) MAIS 1-3 injuries. The costs were adjusted for inflation to 1971 dollars (’71$) based on the annual CPI (Consumer Price Index). A linear trend line was fit to the various costs with the goodness of fit given by the correlation coefficient (R).

RESULTS: The societal cost (C) of motor vehicle crashes was $339.8B in 2019 up from $46.0B in 1971. This was a 7.39-fold increase, or 13.0%/yr annual increase. The linear fit gave C = $6.19B (yr – 1,967), R = 0.978. The compound increase was 4.14%/yr. The injury HARM cost (H) from fatal and nonfatal injuries was $309.1B in 2019 up from $38.1B in 1971. This was an 8.01-fold increase, or 14.3%/yr annual increase. The linear fit gave H = $5.63B (yr – 1,968), R = 0.972. The compound increase was 4.64%/yr. After adjusting for inflation, the societal cost was ’71$52.5B in 2019. This was a 1.142-fold increase or 0.291%/yr annual increase. The linear fit gave C (’71$) = $0.283B (yr – 521), R = 0.554. The ’71$ compound increase was 0.200%/yr. HARM cost increased to ’71$47.8B in 2019. This was a 1.238-fold increase or 0.486%/yr annual increase. The linear fit gave H (’71$) = $0.333B (yr – 625), R = 0.62. The ’71$ compound increase was 0.644%/yr. The greatest increase in injury costs was for MAIS 2-4 injuries with only a modest increase in a fatality cost from $200,700 in 1971 to ’71$247,442 in 2019. NHTSA added quality of life costs to the economic costs giving a high value for a statistical life (VSL), increasing the value of life in cost-benefit analyses.

CONCLUSIONS: The societal cost and injury HARM from motor vehicle crashes increased above inflation over the past 50 years. NHTSA should set 5-year targets and track long-term trends for fatalities and HARM. Cost-benefit analyses depend on VSL, which is based on a willingness to pay. VSL over-values a life. NHTSA over- and under-counts injuries and deaths. The societal costs do not adequately address criminal and insurance fraud, like the Queens and helpful wave schemes, malingering, manipulation of medical imaging and treatments, victim psychology, Lithuanian experiences, and product liability.

PMID:42160709 | DOI:10.1080/15389588.2026.2663051

Folia Morphol (Warsz). 2026;85:e01726095. doi: 10.5603/fm.112025.

ABSTRACT

BACKGROUND: Accurate characterization of fetal thoracic development is essential for improving prenatal assessment and early detection of structural abnormalities. The aim of this study was to evaluate the morphometric and proportional characteristics of the fetal thoracic cavity during mid and late gestational periods.

MATERIALS AND METHODS: A total of 32 fetal specimens (16 mid gestation, 16 late-gestation) were included. Crown-rump length (CRL), transverse diameter (TD), anteroposterior diameter (AP), and thoracic circumference (TC) were measured and analyzed using descriptive statistics, between-group comparisons, correlation, and regression methods.

RESULTS: All parameters increased significantly from mid to late gestation (p < 0.001). The greatest relative growth was observed in TD (≈55%), indicating that transverse expansion represents the dominant pattern of thoracic development. Regression analysis demonstrated that in mid gestation, TC could be reliably predicted by TD alone, whereas in late gestation the inclusion of AP improved predictive accuracy, reflecting increasing structural complexity. Minimal clinically important difference (MCID) analysis confirmed that these changes were not only statistically significant but also clinically meaningful.

CONCLUSIONS: Fetal thoracic development follows stage-specific growth patterns with important clinical implications. The findings provide preliminary data that may support improved prenatal evaluation, the establishment of population-specific normative data, and enhanced prediction of fetal respiratory system maturity.

PMID:42160706 | DOI:10.5603/fm.112025

Folia Morphol (Warsz). 2026;85:e01726096. doi: 10.5603/fm.111811.

ABSTRACT

BACKGROUND: Failure of inferior alveolar nerve block may be attributable to anatomical variations in the location of the mandibular foramen. This study aimed to determine the 3D location of the mandibular foramen (MF) using cone-beam computed tomography (CBCT) and compare the measurements across different sagittal facial types in Asians.

MATERIALS AND METHODS: CBCT scans of 60 mandibles (10 retrognathic, 10 normal, 10 prognathic per gender) were analyzed. The injection pathway was simulated as a line through MF and contralateral lower premolar (MF-cL4). The distances from MF to ramus borders and the angles between MF-cL4 and the mid-sagittal plane (MSP), the mandibular plane (MP) and the lower occlusal plane (LOP) were measured. Data analysis was conducted using descriptive statistics and two-way ANOVA.

RESULTS: Distances from MF to the ramus borders were significantly greater in males than in females (p < 0.05). The distance between MF and the sigmoid notch of prognathic mandibles was greater than in normal/retrognathic types (p < 0.05). Angle MF-cL4-MSP was highly stable at 50.9° ± 2.9°, whereas angle MF-cL4-LOP exhibited significant individual variation with a coefficient of variation (CV) of 63.9%.

CONCLUSIONS: In Asians, MF was consistently located within the upper posterior quadrant of the ramus. Its anteroposterior position remains stable when referenced to MSP and cL4. In prognathic mandibles, MF positioned inferiorly relative to normal and retrognathic mandibles.

PMID:42160705 | DOI:10.5603/fm.111811

J Trop Pediatr. 2026 Apr 11;72(3):fmag031. doi: 10.1093/tropej/fmag031.

ABSTRACT

Preterm birth remains a leading cause of neonatal mortality, disproportionately affecting low-and middle-income countries (LMICs). Surfactant replacement therapy (SRT) is a key intervention for neonatal respiratory distress syndrome (RDS). However, due to cost and differing guidelines there are likely differences in SRT in different parts of the world. This study compared surfactant use, timing of administration, and associated neonatal outcomes in very low birth weight (VLBW) infants born in high-income countries (HICs) versus middle-income countries (MICs), with further analysis of public and private centers within MICs. This secondary analysis of prospectively collected data using the Vermont Oxford Network database included 271 826 inborn VLBW infants from 2018 to 23. Data were stratified by country income classification and ownership (public center vs. private center) in MICs. Surfactant use was highest in private MIC centers (64.1%), followed by HICs (55.3%), and public MIC centers (43.5%). Median time to first surfactant dose was shortest in private MIC centers (60 min) and longest in public MIC centers (120 min). Infants in HICs were more likely to receive delivery room continuous positive airway pressure and earlier surfactant. Survival post-SRT was highest in HICs (88.1%) and lowest in public MIC centers (69.5%) with sepsis being a particular problem in MICs. Disparities in the proportion of infants receiving SRT, the timing of doses, and neonatal outcomes such as mortality and sepsis rates persist between HICs and MICs, and between public and private sectors in MICs.

PMID:42160703 | DOI:10.1093/tropej/fmag031

JCO Glob Oncol. 2026 May;12(5):e2500317. doi: 10.1200/GO-25-00317. Epub 2026 May 20.

ABSTRACT

PURPOSE: The combination of venetoclax (VEN) and a hypomethylating agent (HMA) is a standard of care for patients with AML and higher-risk myelodysplastic syndromes (MDS). However, real-world outcomes data from low- and middle-income countries are scarce, where constraints in advanced diagnostics, financial resources, and supportive care infrastructure present unique challenges. This study evaluates the efficacy and safety of this regimen in a resource-limited setting.

MATERIALS AND METHODS: We conducted a retrospective analysis of 96 patients (AML, n = 54; MDS, n = 42) treated with HMA + VEN at a single center between January 2020 and December 2024. Key outcomes included overall survival (OS), disease-free survival (DFS), and response rates, assessed per standard criteria.

RESULTS: The median age was 52 years for patients with AML and 51 years for patients with MDS. In the AML cohort, OS was 77.4% and DFS was 52.8% at 2 years. The overall response rate (ORR) reached 66.6% at end of treatment (EOT), with 55.5% achieving complete remission. In the MDS cohort, 2-year OS was 59.5% and DFS was 44.4%. The most common major toxicity was febrile neutropenia (AML: 66.7%; MDS: 54.8%), although no related mortality occurred. A minority of patients underwent consolidative transplant (AML: 12.9%; MDS: 21.4%). Statistical analysis identified EOT ORR and VEN maintenance as significant for AML OS, while relapse was a critical factor for MDS OS.

CONCLUSION: The HMA-VEN combination is a highly effective and feasible treatment for AML and MDS, even within a resource-limited setting. The findings underscore the critical need for improved supportive care measures, expanded access to molecular diagnostics for risk stratification, and the development of individualized treatment strategies to optimize patient outcomes.

PMID:42160693 | DOI:10.1200/GO-25-00317