Category: Statistics

JMIR Med Inform. 2025 May 21;13:e63906. doi: 10.2196/63906.

ABSTRACT

BACKGROUND: Despite wide acceptance in medical research, implementation of the FAIR (findability, accessibility, interoperability, and reusability) principles in certain health domains and interoperability across data sources remain a challenge. While clinical trial registries collect metadata about clinical studies, numerous epidemiological and public health studies remain unregistered or lack detailed information about relevant study documents. Making valuable data from these studies available to the research community could improve our understanding of various diseases and their risk factors. The National Research Data Infrastructure for Personal Health Data (NFDI4Health) seeks to optimize data sharing among the clinical, epidemiological, and public health research communities while preserving privacy and ethical regulations.

OBJECTIVE: We aimed to develop a tailored metadata schema (MDS) to support the standardized publication of health studies’ metadata in NFDI4Health services and beyond. This study describes the development, structure, and implementation of this MDS designed to improve the FAIRness of metadata from clinical, epidemiological, and public health research while maintaining compatibility with metadata models of other resources to ease interoperability.

METHODS: Based on the models of DataCite, ClinicalTrials.gov, and other data models and international standards, the first MDS version was developed by the NFDI4Health Task Force COVID-19. It was later extended in a modular fashion, combining generic and NFDI4Health use case-specific metadata items relevant to domains of nutritional epidemiology, chronic diseases, and record linkage. Mappings to schemas of clinical trial registries and international and local initiatives were performed to enable interfacing with external resources. The MDS is represented in Microsoft Excel spreadsheets. A transformation into an improved and interactive machine-readable format was completed using the ART-DECOR (Advanced Requirement Tooling-Data Elements, Codes, OIDs, and Rules) tool to facilitate editing, maintenance, and versioning.

RESULTS: The MDS is implemented in NFDI4Health services (eg, the German Central Health Study Hub and the Local Data Hub) to structure and exchange study-related metadata. Its current version (3.3) comprises 220 metadata items in 5 modules. The core and design modules cover generic metadata, including bibliographic information, study design details, and data access information. Domain-specific metadata are included in use case-specific modules, currently comprising nutritional epidemiology, chronic diseases, and record linkage. All modules incorporate mandatory, optional, and conditional items. Mappings to the schemas of clinical trial registries and other resources enable integrating their study metadata in the NFDI4Health services. The current MDS version is available in both Excel and ART-DECOR formats.

CONCLUSIONS: With its implementation in the German Central Health Study Hub and the Local Data Hub, the MDS improves the FAIRness of data from clinical, epidemiological, and public health research. Due to its generic nature and interoperability through mappings to other schemas, it is transferable to services from adjacent domains, making it useful for a broader user community.

PMID:40397930 | DOI:10.2196/63906

J Med Internet Res. 2025 May 21;27:e60284. doi: 10.2196/60284.

ABSTRACT

BACKGROUND: The recent emergence of wearable devices has made feasible the passive gathering of intensive, longitudinal data from large groups of individuals. This form of data is effective at capturing physiological changes between participants (interindividual variability) and changes within participants over time (intraindividual variability). The emergence of longitudinal datasets provides an opportunity to quantify the contribution of such longitudinal data to the control of these sources of variability for applications such as responder analysis, where traditional, sparser sampling methods may hinder the categorization of individuals into these phenotypes.

OBJECTIVE: This study aimed to quantify the gains made in statistical power and effect size among statistical comparisons when controlling for interindividual variability and intraindividual variability compared with controlling for neither.

METHODS: Here, we test the gains in statistical power from controlling for interindividual and intraindividual variability of resting heart rate, collected in 2020 for over 40,000 individuals as part of the TemPredict study on COVID-19 detection. We compared heart rate on weekends with that on weekdays because weekends predictably change the behavior of most individuals, though not all, and in different ways. Weekends also repeat consistently, making their effects on heart rate feasible to assess with confidence over large populations. We therefore used weekends as a model system to test the impact of different statistical controls on detecting a recurring event with a clear ground truth. We randomly and iteratively sampled heart rate from weekday and weekend nights, controlling for interindividual variability, intraindividual variability, both, or neither.

RESULTS: Between-participant variability appeared to be a greater source of structured variability than within-participant fluctuations. Accounting for interindividual variability through within-individual sampling required 40× fewer pairs of samples to achieve statistical significance with 4× to 5× greater effect size at significance. Within-individual sampling revealed differential effects of weekends on heart rate, which were obscured by aggregated sampling methods.

CONCLUSIONS: This work highlights the leverage provided by longitudinal, within-individual sampling to increase statistical power among populations with heterogeneous effects.

PMID:40397926 | DOI:10.2196/60284

J Med Internet Res. 2025 May 21;27:e70641. doi: 10.2196/70641.

ABSTRACT

BACKGROUND: Overhydration is associated with increased morbidity and mortality in patients on peritoneal dialysis (PD). Early detection of overhydration is possible by monitoring hydration metrics, but the critical gap for treatment is obtaining timely and actionable data.

OBJECTIVE: This study compares the detection of overhydration and clinical outcomes in patients on PD using the Chronic Kidney Disease-Peritoneal Dialysis (CKD-PD) smartphone app with standard monitoring and management.

METHODS: An open-label randomized controlled trial was conducted at 3 hospitals in northeast Thailand. Enrolled participants from PD clinics were randomized into 2 equal groups: CKD-PD (App users) and usual management (No-App). Participants or their caregivers in the App group recorded hydration metrics in the CKD-PD app, which were uploaded to a central database monitored by nephrology staff. The No-App group used a handwritten logbook. Both groups had bimonthly clinic visits. The primary outcome was the incidence rate ratio (IRR) for clinical interventions for overhydration. Secondary outcomes included hospitalizations, technique failure, and death.

RESULTS: A total of 208 participants were randomized into App (N=103) and No-App (N=105) groups with the median follow-up time of 11.2 months. Hydration metric upload compliance in the App group was 85.7% (IQR 71.4-95.6). The IRR of overall interventions for overhydration was 2.51 times higher in the App group (95% CI 2.18-2.89; P<.001). Types of clinical interventions for overhydration differed between groups with dietary change and prescription of antihypertensive drugs more frequent in App users and diuretics and change of dialysis prescription more frequent in the No-App group. Hospitalizations were significantly higher in the No-App group due to any cause (adjusted IRR 1.58) and volume overload (adjusted IRR 4.07). There was no significant difference in survival analysis and technique failure between the 2 groups.

CONCLUSIONS: Use of the CKD-PD app improved early detection of overhydration and early treatment interventions, resulting in fewer all-cause and volume overload hospitalizations.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04797195; https://clinicaltrials.gov/study/NCT04797195.

PMID:40397925 | DOI:10.2196/70641

PLoS One. 2025 May 21;20(5):e0323762. doi: 10.1371/journal.pone.0323762. eCollection 2025.

ABSTRACT

BACKGROUND: Antenatal care (ANC) improves maternal and neonatal health. However, less than half of pregnant women in sub-Saharan African (SSA) countries, including Rwanda, attend adequate ANC designed to provide routine care and detect and treat early pregnancy complications. This article explores the women’s views on factors that hinder adherence to ANC visits in Rwanda.

METHODS: This exploratory qualitative research used in-depth interviews to collect data from 22 pregnant women. Data were recorded, transcribed verbatim, and analyzed using a thematic approach.

RESULTS: A Thematic analysis revealed four themes: a) stigma dynamics, b) sociocultural beliefs and practices, c) lack of partner’s support, and d) Challenges to and at the healthcare setting. Unintended pregnancies, multiparity, and early weaning were identified as reasons why participants delayed attending the ANC. Sociocultural practices and beliefs that place women at the center of domestic chores, cultural misbeliefs, the influence of intergenerational behaviours, and social context were also reported as barriers to attending or adhering to ANC visits. The lack of partner support has been reported as a barrier due to existing family conflicts, domestic violence, competing personal priorities of partners over ANC, and fear of partners of HIV tests. They reported several structural barriers, including attendance and adherence to ANC visits, mandatory requirements before receiving ANC, long distance to the health facility, scattered health services within a health facility, long wait times, and negative attitudes and actions of healthcare providers.

CONCLUSIONS: The identified factors hindering pregnant women’s participation in ANC visits are modifiable in progressive countries such as Rwanda. Continued National support could reduce these barriers, increase ANC attendance, and meet the 2030 Sustainable Development Goal 3.

PMID:40397920 | DOI:10.1371/journal.pone.0323762

PLoS One. 2025 May 21;20(5):e0323381. doi: 10.1371/journal.pone.0323381. eCollection 2025.

ABSTRACT

The objectives of this study were to understand how healthcare systems are incorporating equity into performance measurement and to uncover trends that inform healthcare systems’ efforts to advance equity. A national cross-sectional survey was designed and administered during Spring 2022 to evaluate organizational efforts to track and measure health equity. The survey examined clinical and non-clinical health equity metrics/indicators tracked at the executive-level. We identified variation in how health equity is measured. Of the 27 respondents, seven (25.9%) were in the planning phase, nine (33.3%) were in early implementation, seven (25.9%) had practices implemented for one to two years, and four (14.8%) had practices implemented for three or more years. Most systems were tracking clinical metrics and evaluating metrics across subpopulations. Metrics related to chronic disease management and preventive care were mentioned most frequently (23.6% and 16.0%, respectively). Race/ethnicity was the most utilized demographic filter to evaluate equity. Systems at later stages of implementation were tracking fewer metrics, yet many systems were still in early stages of implementation. Health systems need specific and pragmatic guidance to develop and implement equity measures tracked at the executive level. Insights from current health system initiatives can help inform guidelines from national quality organizations for disparity reduction in clinical outcomes.

PMID:40397918 | DOI:10.1371/journal.pone.0323381

PLoS One. 2025 May 21;20(5):e0324129. doi: 10.1371/journal.pone.0324129. eCollection 2025.

ABSTRACT

This study was conducted to determine and compare the effects of reformer pilates (RP) and mat pilates (MP) exercises on soccer players’ physical parameters and technical skills. Thirty voluntary participants were randomly assigned to either RP group (n = 10; age = 20.60 ± 1.65), MP group (n = 10; age = 19.40 ± 1.35) and control group (CG) (n = 10; age = 20.10 ± 1.15). Technical and physical performance tests were performed. In the RP group counter movement jump (CMJ), standing broad jump (SBJ), single leg triple hop right-left, balance right-left leg, flexibility, 10-20m sprint, german agility (GA), speed dribbling (SPD), loughborough soccer passing (LSPT), lobbed passing right food, lobbed passing total measurement results showed a statistically significant difference between pre-test and post-test mean values (p < 0.05). In the MP group, balance right-left leg, single leg triple hop right-left, 5 – 10m sprint, GA, SPD, LBP, lobbed passing right measurement results showed a statistically significant difference between pre-test and post-test mean values (p < 0.05). The control group had no significant difference in the pre-test and post-test mean values of technical and physical performance measurements (p > 0.05). Between-group comparisons revealed superior improvements in GA, LSPT, and single-leg triple hop right-left in the RP group compared to the MP group. Based on these findings, coaches and sports performance specialists may enhance athletes’ physical performance and technical skills by incorporating Pilates exercises (particularly RP) into training programs.

PMID:40397911 | DOI:10.1371/journal.pone.0324129

JMIR Res Protoc. 2025 May 21;14:e67678. doi: 10.2196/67678.

ABSTRACT

BACKGROUND: Given the high prevalence of coronary heart disease among older adults and aging populations, there is a need for secondary prevention interventions to help older adults become more physically active. Web-based interventions could be considered for this purpose, knowing that internet use is growing rapidly among older adults. In addition, since older adults would appreciate developing a trusting relationship with a nurse, web-based interventions should include this support, which is not widely observed in the literature.

OBJECTIVE: This study aims to evaluate a web-based nursing intervention aimed at promoting physical activity in people 65 years and older with coronary heart disease.

METHODS: A web-based nursing intervention was developed according to the Intervention Mapping framework in collaboration with a team of health care professionals (n=5) and based on the needs of older adults (n=10). The 7-week intervention (1 session per week) aims to support older adults living with coronary artery disease in resuming, maintaining, or increasing their level of physical activity after coronary bypass surgery or percutaneous coronary intervention. The intervention offers educational content on coronary heart disease and physical activity, suggestions for physical activity, reflective activities, case histories of older adults who have experienced different journeys, an electronic physical activity diary to track progress, and support from a nurse through feedback to increase knowledge, motivation, and sense of self-efficacy. The preliminary effects and impacts of the intervention will be assessed through a mixed method pilot study with a sequential explanatory design. First, a single-group pre-post test will be used to assess the intervention’s preliminary effects on physical activity (electronic journal), quality of life (36-Item Short Form Health Survey version 2), knowledge (quiz), motivation, and self-efficacy (visual analog scale) of 30 older adults living with coronary heart disease, as well as the feasibility of the intervention. Second, a descriptive qualitative design will use semistructured interviews to assess the intervention’s impacts as perceived by 8-12 older adults and its acceptability. Quantitative data on the effects of the intervention will be integrated with the collection and analysis of qualitative data to assess the impact perceived by older adults, using matrices. Nonparametric statistics and a thematic analysis will be produced. A joint display will be used to integrate mixed data.

RESULTS: The results of this study will provide insight into the preliminary evaluation of a web-based nursing intervention to support older adults living with coronary heart disease as they increase their physical activity levels. The recruitment commenced in June 2024, and data collection should be completed by June 2025.

CONCLUSIONS: With the potential to promote older adults’ health, this study could guide the development of new interventions to meet the needs of an aging population.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06197347; https://clinicaltrials.gov/study/NCT06197347.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/67678.

PMID:40397502 | DOI:10.2196/67678

JAMA Cardiol. 2025 May 21. doi: 10.1001/jamacardio.2025.1101. Online ahead of print.

ABSTRACT

IMPORTANCE: Patients with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) less than 40% who experience LVEF improvement to 40% or higher (HFimpEF) may still face residual risks.

OBJECTIVE: To assess the clinical profiles, risk, and treatment response to finerenone in participants with HFimpEF.

DESIGN, SETTING, AND PARTICIPANTS: A total of 6001 patients with HE, LVEF of 40% or higher, New York Heart Association class II to IV symptoms, and elevated natriuretic peptide levels, were enrolled between September 14, 2020, and January 10, 2023. Patients with a prior history of LVEF less than 40% were included. Data analysis was conducted between September 1 to December 10, 2024.

INTERVENTION: Participants received finerenone (titrated to 20 mg or 40 mg) or placebo.

MAIN OUTCOMES AND MEASURES: The primary end point was the composite of cardiovascular (CV) death and total (first and recurrent) worsening HF events.

RESULTS: Of the 6001 participants (mean [SD] age, 72 [9.7], years; 3269 male [55%]), 273 (5%) had a prior LVEF less than 40%. Among those with a prior LVEF of less than 40%, the median recorded prior LVEF was 35% [IQR, 30%-37%], with a median improvement of 12% [IQR, 8%-17%]. Over a median follow-up of 2.6 years, those with a history of LVEF of less than 40% experienced higher rates of the primary outcome of a composite of CV death and worsening of HF events (21.4 per 100 patient-years vs 16.0 per 100 patient-years) than did those whose LVEF was consistently 40% or higher. After adjustment for clinically relevant covariates; however, this rate ratio (RR) was not statistically different (absolute RR, 1.13; 95% CI, 0.85-1.49, P = .39). The treatment effect of finerenone on the primary outcome was consistent among those with a history of LVEF less than 40% and those with LVEF that was consistently 40% or higher (P for interaction = .36). Owing to higher baseline risk, the absolute risk reduction was greater among those with HFimpEF (9.2 vs 2.5 per 100 patient-years). Patients with HFimpEF tended to develop more hypotension with finerenone treatment, but otherwise, the safety profile of finerenone was similar in patients with and without previous LVEF less than 40%.

CONCLUSIONS AND RELEVANCE: In this prespecified analysis of a randomized clinical trial, patients with HFimpEF remained at high risk of CV events, underscoring the need for continued management despite LVEF improvement. The treatment benefits of finerenone observed among the overall population of patients with HF with preserved EF were consistent among patients with HFimpEF.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

PMID:40397470 | DOI:10.1001/jamacardio.2025.1101

JAMA Cardiol. 2025 May 21. doi: 10.1001/jamacardio.2025.1182. Online ahead of print.

ABSTRACT

IMPORTANCE: Peripheral artery disease (PAD) is a heritable atherosclerotic condition associated with functional decline and high risk for limb loss. With growing knowledge of the genetic basis for PAD and related risk factors, there is potential opportunity to identify individuals at high risk using polygenic risk scores (PRSs).

OBJECTIVE: To develop a novel integrated, multiancestry polygenic score for PAD (PRS-PAD) and evaluate its risk estimation for PAD and major adverse limb events in 3 populations.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study was conducted among individuals with genotyping and electronic health record data in the UK Biobank (2006-2021), All of Us (AoU, 2018-2022), and the Mass General Brigham Biobank (MGBB, 2010-2023). Data were analyzed from July 2023 to February 2025.

EXPOSURES: PRS-PAD, previously published PAD polygenic scores, and clinical risk factors.

MAIN OUTCOMES AND MEASURES: The primary outcomes were PAD and major adverse limb events, defined as a surrogate of major amputation and acute limb ischemia.

RESULTS: The study populations included 400 533 individuals from the UK Biobank (median [IQR] age, 58.2 [45.0-71.4] years; 216 215 female participants [53.9%]), 218 500 from AoU (median [IQR] age, 53.6 [37.7-65.0] years; 132 647 female participants [60.7%]), and 32 982 from MGBB (median [IQR] age, 56.0 [32.0-80.0] years; 18 277 female participants [55.4%]). In the UK Biobank validation cohort, PRS-PAD was associated with an odds ratio [OR] per SD increase of 1.63 (95% CI, 1.60-1.68; P < .001). After adjusting for clinical risk factors, the OR for the top 20% of PRS-PAD was 1.68 (95% CI, 1.62-1.74; P < .001) compared to the remainder of the population. Among PAD cases without a history of diabetes, smoking, or chronic kidney disease (n = 3645), 1097 individuals (30.1%) had a high PRS-PAD (top 20%). In incident disease analysis, PRS-PAD improved discrimination (C statistic, 0.761), which was nearly equivalent to the performances of diabetes (C statistic, 0.760) and smoking (C statistic, 0.765). Among individuals with prevalent PAD, high PRS-PAD was associated with an increased risk of incident major adverse limb events in the UK Biobank (hazard ratio [HR], 1.75; 95% CI, 1.18-2.57; P = .005), MGBB (HR, 1.56; 95% CI, 1.06-2.30; P = .02), and AoU (HR, 1.57; 95% CI, 1.06-2.33; P = .03).

CONCLUSIONS AND RELEVANCE: This cohort study develops a new PRS that stratifies risk of PAD and adverse limb outcomes. Incorporating polygenic risk into PAD care warrants further investigation to guide screening and tailor management to prevent major adverse limb events.

PMID:40397457 | DOI:10.1001/jamacardio.2025.1182

Chembiochem. 2025 May 21:e202500209. doi: 10.1002/cbic.202500209. Online ahead of print.

ABSTRACT

Clozapine is an excellent antipsychotic that has been widely used to treat conventional antipsychotic-refractory schizophrenia. Since a body of evidence indicates the involvement of the dysfunction of the N-methyl-D-aspartate type glutamate receptor (NMDAR) in the pathophysiology of antipsychotic-resistant and responsive symptoms of schizophrenia, we have explored the exact mechanisms underlying the superior clinical efficacy of clozapine by studying the effects of clozapine on brain extracellular signaling of NMDAR-related amino acids in the rat medial prefrontal cortex using an in vivo dialysis technique by a quantitative HPLC detection method. Intra-peritoneal injection of clozapine (5, 10 and 20 mg/kg) failed to affect the prefrontal extracellular levels of D-serine, a coagonist for the NMDAR acting at the glycine site, and its precursor, L-serine, from 20 to 160-min post-injection The cortical extracellular concentrations of glycine, another NMDAR coagonist, and L-arginine, a nitric oxide/NMDAR pathway-associated factor, were significantly reduced by 10mg/kg of clozapine. Clozapine administration (20 mg/kg) nominally elevated the prefrontal extracellular levels of L-glutamate, which was not statistically significant after multiple comparisons. The present findings are consistent with the view that clozapine could influence the NMDAR function, at least in part, through modulation of the prefrontal cortical extracellular levels of glycine, L-arginine and glutamate.

PMID:40397451 | DOI:10.1002/cbic.202500209