Category: Statistics

Cardiovasc Diabetol. 2026 May 9. doi: 10.1186/s12933-026-03180-6. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular-kidney-metabolic (CKM) syndrome are interrelated conditions with shared pathophysiological features; however, the genetic architecture underlying their relationship has not been fully elucidated. Deciphering this shared genetic basis holds promise for advancing mechanistic insights and therapeutic discovery.

METHODS: We performed an integrated genome-wide cross-trait analysis using GWAS summary statistics for MASLD and 38 CKM traits. Our analysis estimated genetic correlations, inferred causal relationships, and identified pleiotropic variants. Candidate causal genes and druggable targets were subsequently prioritized through integrating multi-omics data.

RESULTS: MASLD exhibited significant genetic correlations with 16 CKM traits, especially metabolic and cardiovascular conditions. Bidirectional causal relationships were observed between MASLD and T2D, adiposity, and lipid traits. We discovered 116 pleiotropic loci, including 65 shared causal variants such as rs429358 near APOE, which exerted influence across multiple traits. Gene-based analyses prioritized 152 unique candidate pleiotropic genes, enriched in lipid and cholesterol metabolism, and highly expressed in the liver, adipose, and immune-related cell types, such as macrophages and endothelial cells. Multi-omics integration validated 131 genes using eQTL and pQTL data from multiple tissues and cohorts. Notably, FTO and APOE emerged as central pleiotropic hubs, and druggability evaluation highlighted APOE, LPL, PPARG, and GPBAR1 as established therapeutic targets for metabolic diseases.

CONCLUSION: This study provides a comprehensive map of the shared genetic architecture between MASLD and CKM syndrome, reveals novel causal genes and repurposable drug targets, and offers insights into precision medicine approaches for cardiometabolic and liver diseases.

PMID:42106791 | DOI:10.1186/s12933-026-03180-6

BMC Health Serv Res. 2026 May 9. doi: 10.1186/s12913-026-14617-9. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical pathways are increasingly adopted to control costs and enhance quality management, becoming a standardized approach in treatment. This study aims to develop a hospital-specific clinical pathway for non-small cell lung cancer (NSCLC) surgery based on national standards and actual treatment practices, and evaluate its service efficiency through simulation.

METHODS: We analyzed 94 electronic medical records of NSCLC surgeries performed between May 2020 and November 2022, evaluating the need for localization by statistically examining treatment process delays. A Time Petri Net model was established for this pathway, with simulations conducted to measure post-implementation changes in hospital length of stay (LOS).

RESULTS: The hospital’s existing processes were generally consistent with national standards. Validation of the Time Petri Net model confirmed its effectiveness. Simulation results showed that the average LOS was reduced from a baseline of 8.20 days to 7.76 days, saving a total of ~ 10.28 h (individual diagnostic/treatment processes were shortened by 0.15-5.04 h).

CONCLUSION: Implementing this tailored clinical pathway significantly improved service efficiency by aligning it with national guidelines, enabling better integration and optimization of medical resources while improving overall clinical pathway management quality.

PMID:42106790 | DOI:10.1186/s12913-026-14617-9

BMC Oral Health. 2026 May 9. doi: 10.1186/s12903-026-08360-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect of adding graphene oxide (GO) to HEMA-containing and HEMA-free universal adhesives on water sorption/solubility and bonding effectiveness to dentin.

MATERIALS AND METHODS: GO was incorporated into universal adhesives (Scotchbond Universal and G-Premio Bond) at three weight percentages (0.5, 1, and 3%) and characterized by SEM. Clearfil SE Bond was used as the reference adhesive. Disk-shaped specimens were prepared to evaluate water sorption and solubility (n = 10). Microspecimens were prepared from ninety extracted human third molar. The µTBS of half of the specimens was tested after 24 h, and the remaining specimens were aged for 6 months. Failure mode was analyzed using a stereomicroscope. Statistical analyses were performed with one-way ANOVA, Duncan, and paired t-tests (p = 0.05).

RESULTS: Adding 3% GO increased water sorption of the adhesives (p < 0.05). Clearfil SE Bond exhibited the lowest water sorption and solubility (p < 0.05). 1% GO significantly increased the immediate µTBS of the adhesives, whereas 3% resulted in a significant decrease (p < 0.05). 0.5 and 1% GO significantly increased the aged µTBS of Scotchbond Universal, while only 1% improved the aged µTBS of G-Premio Bond (p < 0.05). 3% GO reduced the aged µTBS of the adhesives (p < 0.05). The highest immediate and aged µTBS were recorded for Clearfil SE Bond (p < 0.05).

CONCLUSIONS: The bonding performance of universal adhesives improved with 0.5% and 1% GO additions, whereas 3% GO had a detrimental effect on both bond strength and water sorption.

CLINICAL SIGNIFICANCE: Adding GO to adhesives may improve the long-term durability of bonded restorations.

PMID:42106783 | DOI:10.1186/s12903-026-08360-0

Int J Gynaecol Obstet. 2026 May 9. doi: 10.1002/ijgo.71071. Online ahead of print.

ABSTRACT

OBJECTIVE: This study assesses the changing patterns of domestic, sexual, and gender-based violence (DSGBV) among survivors managed at a dedicated referral center in North-East Nigeria over a 5-year period (2021-2025).

METHODS: A retrospective descriptive study was conducted at the Gender-Based Violence Unit of the Specialist Hospital Gombe. Records of all survivors of DSGBV managed between January 1, 2021, and December 31, 2025, were reviewed. Data on year of presentation, age, sex, type of violence, place of residence, and time of reporting were extracted. Descriptive statistics were used to summarize trends and distributions. Inferential analysis was performed using IBM SPSS version 26 (IBMCorporation, Armonk, NY, USA). This study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

RESULTS: A total of 675 survivors were recorded, with a progressive increase from 79 cases in 2021 to 171 in 2025. Adolescents aged 10-14 years consistently accounted for the highest proportion of cases (196/675; 29%). Females constituted 81.6% (551/675) of survivors. Sexual violence was the predominant form of abuse (556/675; 82.3%). Most survivors (601/675; 89.0%) resided in rural areas. Delayed reporting beyond 72 h was the most common pattern across all years.

CONCLUSION: Reported cases of DSGBV increased progressively over 5 years, with children and adolescents bearing a disproportionate burden and sexual violence predominating. These findings highlight the need for strengthened routine screening, provider training, and equitable access to survivor-centered services, particularly for rural and adolescent populations in conflict-affected settings.

PMID:42104841 | DOI:10.1002/ijgo.71071

Health Serv Res. 2026 Jun;61(3):e70124. doi: 10.1111/1475-6773.70124.

ABSTRACT

OBJECTIVE: To examine staff perceptions of a proactive, telephonic transition-of-care pilot model that connects pregnant people with recent emergency department (ED) utilization to early pregnancy-related care (e.g., prenatal care, abortion care, miscarriage support) and community resources. Although pregnant individuals disproportionately seek care in the ED, post-ED discharge models for care navigation remain understudied.

STUDY SETTING AND DESIGN: Between August 2021 and June 2023, six sites (three health systems, two federally qualified health centers, and one community-based organization) implemented the transition-of-care model with ongoing support from an external organization (‘external facilitator’). We conducted a qualitative descriptive study to explore pilot-engaged staff and leader perspectives regarding intervention fit and contextual factors influencing implementation and sustainability.

DATA SOURCES AND ANALYTIC SAMPLE: From February to March 2024, we conducted interviews with 13 individuals (six outreach champions; four administrative champions; three senior leaders) representing all six pilot sites. Guided by the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework, we employed codebook thematic analysis to identify key themes regarding the extent to which intervention characteristics met patients’ perceived needs and factors influencing pilot site implementation and sustainability.

PRINCIPAL FINDINGS: Pilot site champions and leaders described the transition-of-care model as acceptable and feasible. Key strengths included the pilot model’s patient-centered design (e.g., timely, proactive outreach and individualized support), health information exchange (HIE)-driven ED data infrastructure, and role of the external facilitator. Receipt of coaching and training on sensitive, respectful communication in the early pregnancy period also facilitated program implementation. Adequate outreach staffing acted as a barrier and potential determinant of sustainability.

CONCLUSION: Our findings provide preliminary evidence in support of an outreach model to promote initiation of early pregnancy-related care following ED utilization and offer a flexible blueprint for adaptation across clinical settings. Our work meaningfully contributes to the limited literature base on early pregnancy care innovation.

PMID:42104839 | DOI:10.1111/1475-6773.70124

Clin Trials. 2026 May 9:17407745261438128. doi: 10.1177/17407745261438128. Online ahead of print.

ABSTRACT

Sample size re-estimation designs using a promising zone framework are widely used adaptive trial methodologies that guide study continuation or modification during interim analyses. Conventional implementations often base interim calculations solely on participants with available primary endpoints, overlooking predictive information from baseline and earlier visits. This underutilization can lead to inefficient interim decision-making. In this work, we adapt semi-parametric efficient estimators that leverage baseline and intermediate data for use within a promising zone sample size re-estimation design. By incorporating information from participants who have not yet reached their primary endpoint, these estimators enable more precise interim estimators while maintaining strict Type I error control through the inverse normal combination function. Using data from the ADAPT study in generalized myasthenia gravis, we illustrate how these methods integrate into a promising zone sample size re-estimation framework. Simulations based on longitudinal profiles of anti-acetylcholine receptor antibody-seronegative participants demonstrate improved operating characteristics compared with the conventional approach, including increased overall power, especially for moderate effect sizes, without inflating the one-sided Type I error. Our findings highlight the practical benefit of applying existing semi-parametric estimators within promising zone sample size re-estimation designs, enabling more efficient and timely interim decision-making in settings with partially observed longitudinal data.

PMID:42104835 | DOI:10.1177/17407745261438128

Clin Trials. 2026 May 9:17407745261442586. doi: 10.1177/17407745261442586. Online ahead of print.

ABSTRACT

Covariate adjustment uses baseline prognostic variables to improve the precision of treatment effect estimates. Recent Food and Drug Administration guidance and scientific consensus emphasize three principles for its use, namely estimand-focused analyses, assumption-lean robustness, and fit-for-purpose variance estimation. Despite substantial methodological progress, practical guidance for trial practitioners remains fragmented. We review covariate adjustment strategies for continuous, discrete, and time-to-event endpoints in randomized trials that adhere to these three principles. We show how unadjusted estimators, as well as linear and non-linear adjusted estimators, can be viewed as special cases of the general augmented inverse probability weighting framework. For time-to-event endpoints, we describe how covariate adjustment can be applied to Kaplan-Meier estimators, log-rank tests, and estimation of the unconditional hazard ratio without altering the estimand or introducing additional assumptions. We also synthesize recent developments in multi-arm trials, covariate-adaptive randomization, data-adaptive covariate selection, and covariate adjustment in interim analyses, and we provide practical insights for implementation. Covariate-adjusted estimators target the same marginal estimands as unadjusted analyses but typically achieve greater efficiency. Linear adjustment with Analysis of Heterogeneous Covariance guarantees asymptotic efficiency gains under minimal assumptions. Augmented inverse probability weighting generalizes covariate adjustment to flexible modeling frameworks and remains consistent even under model misspecification. For survival analysis, covariate-adjusted versions of the log-rank test and Cox model improve power without altering the estimand or requiring additional assumptions. Properly accounting for covariate-adaptive randomization is essential for valid inference. The reviewed methods are implemented in the RobinCar family of R packages: RobinCar and RobinCar2. Covariate adjustment is a principled and practical approach for improving trial efficiency, aligned with current regulatory guidance. By adhering to the principles of estimand-focus, assumption-lean robustness, and fit-for-purpose variance estimation, practitioners can apply covariate adjustment with confidence across diverse trial settings. Further work on evaluating finite-sample performance and re-analyses of completed trials will deepen understanding of covariate adjustment in practice.

PMID:42104833 | DOI:10.1177/17407745261442586

Acta Med Port. 2026 May 4;39(5):332-339. doi: 10.20344/amp.24246. Epub 2026 May 4.

ABSTRACT

INTRODUCTION: This study aimed to describe and compare patient-reported outcome measures (PROMs) and objective clinical outcome measures (CROMs) in the treatment of age-related macular degeneration (AMD), exploring the concordance between these measures within a value-based healthcare (VBH) framework.

METHODS: This prospective, multicenter, observational, real-world study was conducted at three tertiary referral hospitals specializing in the treatment of neovascular AMD. Clinical outcomes (CROMs) and patient-reported outcomes (PROMs) were analyzed using the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) questionnaire as a functional assessment tool. Data were collected at baseline and at three, six, and 12 months following initiation of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Statistical analysis was primarily descriptive. The comparison between baseline and 12 months in the global NEI VFQ-25 score was performed using the Wilcoxon signed-rank test for paired samples. Concordance between CROMs and PROMs was assessed using the intraclass correlation coefficient (ICC).

RESULTS: A total of 235 eyes were included, receiving 2338 intravitreal injections. The mean age of participants was 81 years (SD = 8.57), and 55.8% were female. The mean baseline NEI VFQ-25 score was 67.83 (SD = 10.39). The median best-corrected visual acuity was 63 ETDRS letters (interquartile range [P25 – P75]: 41 – 75) at baseline, increasing to 65 letters at three months and remaining stable through 12 months of follow-up. The comparison between baseline and 12 months revealed a statistically significant difference in visual acuity (Wilcoxon signed-rank test, Z = 4.2; p < 0.001). A reduction in the proportion of patients classified as legally blind was observed, together with an increase in the proportion of patients in the reading-vision and driving-vision categories. At 12 months, 58.7% of patients reported stabilization or improvement in visual function on the NEI VFQ-25 questionnaire. Concordance between the variation in visual acuity and the variation in the global NEI VFQ-25 score showed good agreement between CROMs and PROMs (ICC = 0.76; p < 0.001).

CONCLUSION: The integrated analysis of CROMs and PROMs suggests that anti-VEGF treatment for neovascular AMD is associated with stabilization or improvement in visual acuity and patients’ perceived visual function. The implementation of the VBH-AMD model proved feasible in a real-world clinical setting, reinforcing the importance of integrating patient-centered measures into the evaluation of therapeutic outcomes.

PMID:42104825 | DOI:10.20344/amp.24246

Schizophr Bull. 2026 Apr 10;52(3):sbag067. doi: 10.1093/schbul/sbag067.

ABSTRACT

BACKGROUND: People with severe mental illness (SMI) are at an increased risk of infection mortality compared to the general population. Little is known about how this risk might differ across infection types, and the potential impact of sociodemographic and clinical factors. We investigated associations between SMI and infection mortality in a population-based cohort, examining variation by infection type and potential moderating factors.

STUDY DESIGN: This retrospective matched cohort study (January 1, 2000 to December 31, 2019) used national primary care data from the UK Clinical Practice Research Datalink linked with Office of National Statistics mortality data. Competing risks regression and cause-specific hazard models assessed risk of infection mortality in people with SMI versus non-SMI controls. We examined risk across different infection types and assessed the impact of sociodemographic and clinical factors.

STUDY RESULTS: Our cohort comprised 84 494 people with SMI matched on age, gender, and GP practice with 84 494 non-SMI controls. Fully adjusted models showed that people with SMI were more likely to die from any infection compared to non-SMI controls (adjusted hazards ratio (aHR) = 1.58, 95% CI, 1.44-1.74). Infection-specific analyses revealed increased risk of death from respiratory (aHR = 1.69, 95% CI, 1.51-1.89), gastrointestinal (aHR = 2.01, 95% CI, 1.16-3.48), and renal/urinary (aHR = 1.70, 95% CI, 1.32-2.19) infections in the SMI group.

CONCLUSIONS: People with SMI are at increased risk of infection mortality, especially from respiratory, gastrointestinal, and renal/urinary infections. We recommend prioritizing this group for preventative measures including influenza and pneumococcal vaccines.

PMID:42104801 | DOI:10.1093/schbul/sbag067

Schizophr Bull. 2026 Apr 10;52(3):sbag049. doi: 10.1093/schbul/sbag049.

ABSTRACT

BACKGROUND AND HYPOTHESIS: The early phase of psychosis is critical for interventions to modify long-term outcomes. It is unclear what proportion of individuals’ exhibit early persistent psychosis and the long-term implications.

STUDY DESIGN: An epidemiologic sample of individuals with acute psychosis was recruited at first admission and followed for 25 years. Early persistent psychosis was defined as presence of active psychosis for ≥90% of the days of the 4 years after first hospitalization for psychosis. Multivariable regression analyses were conducted, testing the association between baseline predictors and persistent psychosis, and between persistent psychosis and 25-year outcomes.

STUDY RESULTS: Out of 526 individuals (age = 27.4 ± 9.4 years, males = 56.8%, baseline schizophrenia/schizoaffective disorder = 30.0%), 101 (19.2%) had early persistent psychosis. At baseline, low premorbid cognitive performance (odds ratio (OR) = 2.08, 95% CI, 1.05-4.12), lower Global Assessment of Functioning (OR = 1.59, 95% CI, 1.16-2.13), low role function (OR = 1.49, 95% CI, 1.03-2.16) and worse social function (OR = 1.52, 95% CI, 1.03-2.22) were predictive of persistent psychosis. At 25-year follow-up (n = 307, 58.9%), early persistent psychosis was associated with worse avolition ($beta$=0.25, 95% CI, 0.14-0.35), more severe reality distortion ($beta$=0.19, 95% CI, 0.07-0.31), disorganization ($beta$=0.21, 95% CI, 0.09-0.32), worse social ($beta$=-0.18, 95% CI, -0.06 to -0.30), role ($beta$=-0.22, 95% CI, -0.09 to -0.34), and global function ($beta$=-0.28, 95% CI, -0.17 to -0.38), greater odds of being on public assistance (OR = 2.13, 95% CI, 1.15-3.95), lower odds of living independently (OR = 0.43, 95% CI, 0.23-0.80) or recovery (OR = 0.09, 95% CI, 0.02-0.38).

CONCLUSIONS: One in 5 individuals with first-episode psychosis had early persistent psychosis without clearly modifiable premorbid factors, and with strong associations with adverse long-term outcomes. Individuals experiencing early persistent psychosis require focused long-term interventions.

PMID:42104800 | DOI:10.1093/schbul/sbag049