Category: Statistics

Hepatol Commun. 2025 Dec 1;9(12):e0832. doi: 10.1097/HC9.0000000000000832. eCollection 2025 Dec 1.

ABSTRACT

BACKGROUND: The impact of acute-on-chronic liver failure (ACLF), a deadly form of decompensated cirrhosis characterized by the presence of organ failures, has not been well characterized, largely due to the lack of a code for ACLF in the International Classification of Diseases (ICD). We used ICD codes for extrahepatic organ failure to assess the burden of cirrhosis with extrahepatic organ failures (EHOFs) on European health care systems.

METHODS: The authors have searched national healthcare system databases from Germany for the period 2005-2020 and matched the data with that from France, Italy, and Denmark for admissions between 2017 and 2020, specifically for cases with an ICD diagnosis of cirrhosis combined with kidney, brain, respiratory, or circulatory failure.

RESULTS: During the 4-year period, 1,599,680 hospital admissions for cirrhosis, which included 329,093 (20.6%) admissions with at least 1 EHOF, were recorded across the 4 countries. The most frequent failing organs were kidneys (52.9%) and respiration (41.2%). The annual number of admissions for cirrhosis decreased over time (from 414,093 to 375,112), whereas the percentage of admissions with EHOF rose from 19.9% to 21.5%. Overall, the in-hospital mortality rate of patients with a diagnosis of EHOF was high (29.2%), markedly exceeding the mortality of those with a diagnosis of cirrhosis (7.9%). The proportion of estimated total healthcare claims of all hospital admissions of EHOF from cirrhosis was 44.9%.

CONCLUSIONS: This study reveals that the burden of cirrhosis with EHOF was high in the 4 European countries, with a substantial impact on patient mortality. Crucially, these findings underscore the significant economic strain placed on healthcare systems by EHOF in cirrhosis patients. This should motivate all stakeholders to take action aiming at reducing this burden.

PMID:41985063 | DOI:10.1097/HC9.0000000000000832

Brief Bioinform. 2026 Mar 1;27(2):bbag175. doi: 10.1093/bib/bbag175.

ABSTRACT

Advances in single-cell sequencing and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technologies have enabled detailed case-control comparisons and experimental perturbations at single-cell resolution. However, uncovering causal relationships in observational genomic data remains challenging due to selection bias and inadequate adjustment for unmeasured confounders, particularly in heterogeneous datasets. To address these challenges, we introduce causarray, a robust causal inference framework for analyzing array-based genomic data at both pseudo-bulk and single-cell levels under unmeasured confounding. causarray integrates a generalized confounder adjustment method to account for unmeasured confounders and employs semiparametric inference with flexible machine learning techniques to ensure robust statistical estimation of treatment effects. Benchmarking results show that causarray robustly separates treatment effects from confounders while preserving biological signals across diverse settings. We also apply causarray to two single-cell genomic studies: (i) an in vivo Perturb-seq study of autism risk genes in developing mouse brains and (ii) a case-control study of Alzheimer’s disease (AD) using three human brain transcriptomic datasets. In these applications, causarray identifies clustered causal effects of multiple autism risk genes and consistent causally affected genes across AD datasets, uncovering biologically relevant pathways directly linked to neuronal development and synaptic functions that are critical for understanding disease pathology.

PMID:41985059 | DOI:10.1093/bib/bbag175

JMIR Diabetes. 2026 Apr 15;11:e85083. doi: 10.2196/85083.

ABSTRACT

BACKGROUND: Patients with type 2 diabetes mellitus (T2D) have a higher risk of cardiovascular disease, including heart failure (HF), leading to health care burden including hospitalization and mortality. Among multiple T2D therapies, there are inadequate head-to-head comparisons of their effects on HF in the real-world patient population.

OBJECTIVE: This study aims to compare the time-to-HF among patients treated with different T2D drugs following metformin.

METHODS: We conducted a retrospective data analysis on electronic health records of 5000 patients with T2D. The inclusion criteria were previous treatment with metformin and initiation of glucagon-like peptide-1 receptor agonists (GLP1 RAs), dipeptidyl peptidase-4 inhibitors (DPP4i), sulfonylureas, or insulin. We grouped patients by the mechanism of their subsequent therapies and focused on 2 pairs of comparisons classified by insulin resistance: sulfonylureas versus insulin (increased resistance) and GLP1 RA versus DPP4i (decreased resistance). The outcomes were 5-year HF status and the HF-free survival time, which was verified manually by examining clinical notes. We applied doubly robust causal estimation and accounted for confounding by adjusting for coded and natural language processing electronic health record features identified through medical knowledge networks.

RESULTS: The study included 939 patients, of whom 204 (21.7%) received insulin, 482 (51.3%) received sulfonylureas, 90 (9.6%) received GLP1 RA, and 163 (17.4%) received DPP4i. Patients in the sulfonylureas group had a significantly higher 5-year HF-free survival compared to the insulin group (survival ratio of insulin/sulfonylureas 0.902, 95% CI 0.840-0.976; P=.01). There was no significant difference between the DPP4i versus GLP1 RA group in 5-year HF-free survival (survival ratio of GLP1 RA/DPP4i was 0.953, 95% CI 0.849-1.067; P=.40). For the occurrence of a HF-related hospitalization within 5 years, there were no significant differences between the sulfonylureas and insulin groups (risk difference 0.057, 95% CI -0.011 to 0.132; P=.11), and between the GLP1 RA and DPP4i groups (risk difference 0.010, 95% CI -0.096 to 0.129).

CONCLUSIONS: We evaluated real-world evidence on 2 head-to-head comparisons of second-line T2D therapies on 5-year HF outcomes. Patients on sulfonylureas were associated with lower 5-year HF risks than those treated with insulin when measured by risk ratio, but no significant difference was detected when measured by the risk difference. Limitations of this study included potentially inadequate adjustment of confounding in the observational study and a limited sample size with validated HF outcomes.

PMID:41985055 | DOI:10.2196/85083

J Sex Med. 2026 Apr 9;23(5):qdag100. doi: 10.1093/jsxmed/qdag100.

ABSTRACT

BACKGROUND: Prostate cancer remains one of the most common cancers in men, and while active surveillance using serial prostate-specific antigen (PSA), imaging, and biopsies is the preferred management for low-risk cases, concerns remain about the impact of biopsy-related sexual dysfunction due to proximity to neurovascular bundles.

AIM: To evaluate the association in biopsy frequency and sexual function in men on active surveillance (AS) for low-grade prostate cancer.

METHODS: We analyzed data from the Miami Active Surveillance Trial (MAST, a prospective, single-arm study of men with Gleason grade ≤2 prostate cancer under AS, managed with annual magnetic resonance imaging-ultrasound fusion-guided transrectal ultrasound (TRUS) biopsies. Sexual and hormonal function was assessed using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline and 12-, 24-, and 36-month follow-ups. Minimally important differences (MID) were defined as 10-12 points for the sexual domain, and 4-6 points for the hormonal domain. Statistical analysis involved repeated measures analysis of variance (ANOVA) and paired t-tests using distribution of EPIC scores.

OUTCOMES: Annual transrectal biopsies were associated with small, statistically, but not clinically significant declines in sexual function, with no meaningful impact on overall quality of life observed.

RESULTS: Among 200 men enrolled, the median age was 62 years old, 89.5% were white, and 43% were Hispanic. A total of 52 men completed all follow-up biopsies. The mean baseline sexual function score was 43.7 (SD 13.1). Repeated measures ANOVA indicated a statistically significant decline in sexual function over time (P = .0105). Though statistically significant, this decline did not exceed the MID threshold for the sexual domain and therefore not clinically significant. Hormonal scores remained stable and showed no significant difference across time points (P = .5767).

CLINICAL IMPLICATIONS: These findings support annual biopsy usage in AS protocols for clinicians without compromising sexual function.

STRENGTHS & LIMITATIONS: The strengths of this study include rigorous annual biopsy protocols and validated EPIC measures to identify clear clinically significant thresholds. Limitations include sample attrition over time due to longer follow-up and single-institution design.

CONCLUSION: Increased frequency of TRUS biopsies was associated with a statistically, but not clinically significant decline in sexual function, indicating that annual TRUS fusion biopsies are not likely to significantly impact sexual health and may be confidently recommended for patients on active surveillance.

PMID:41985042 | DOI:10.1093/jsxmed/qdag100

A A Pract. 2026 Apr 15;20(4):e02183. doi: 10.1213/XAA.0000000000002183. eCollection 2026 Apr 1.

ABSTRACT

BACKGROUND: Preoperative chart review is time-consuming and prone to errors, particularly for cardiopulmonary conditions that impact anesthetic planning. We developed a guideline-aligned “clinical insight bot” that mines free-text documentation to surface perioperative cardiovascular risk signals relevant to the 2024 Mult Society perioperative guideline for noncardiac surgery.

METHODS: We analyzed 1000 de-identified medical cases from the PhysioNet MIMIC database. Medical terminology was extracted using regex-based NLP and categorized into 13 clinical specialties. Text features were encoded using TF-IDF vectorization and 1536-dimensional semantic embeddings stored in a PostgreSQL vector database (pgvector). Four machine learning models-Logistic Regression, Random Forest, Support Vector Machine (SVM), and Naive Bayes-were trained with stratified fivefold cross-validation to classify cases as “cardiopulmonary-only” versus “mixed/other.” Performance was evaluated using accuracy, precision, recall, and F1 score, with statistical comparison via McNemar’s test and bootstrap confidence intervals.

RESULTS: In a held-out test set of 200 notes (28 positive; 172 negatives; ~14% prevalence), a linear support vector machine achieved the best overall balance (F1 ≈ 0.71), with high precision (positive predictive value 0.94) and very low false positive rate (FPR) (1/172 ≈ 0.6%). False negatives were the dominant residual error class. The pipeline processed documents near-instantaneously and, when scaled to 1000 notes, replaced on the order of tens of clinician review hours (≈100× efficiency gain) while maintaining performance across common preoperative document types.

CONCLUSIONS: A lightweight, guideline-aligned insight bot can transform unstructured preoperative notes into concise, stepwise prompts that flag cardiovascular risk signals before the day of surgery. High precision with a very low FPR supports safe integration with anesthesiology workflows by minimizing paging noise, whereas time savings create operational and financial value. Future work should emphasize multicenter validation, structured data fusion (including labs, imaging, and vitals) to improve sensitivity, and prospective evaluation of downstream clinical and operational outcomes.

PMID:41985030 | DOI:10.1213/XAA.0000000000002183

Adv Sci (Weinh). 2026 Apr 15:e22070. doi: 10.1002/advs.202522070. Online ahead of print.

ABSTRACT

Ecosystem services (ES) link ecosystems and human societies, yet approaches to ecosystem service flow (ESF) are constrained by ambiguous definitions and limited process-oriented and scale-sensitive classifications. Here, we developed a “supply-demand-flow” framework distinguishing potential and actual supply and demand, and classifying ESF into in situ, interior, and exterior flows. Integrating multi-source datasets, biophysical models (InVEST, RUSLE, i-Tree), and socio-economic accounting based on population-consumption dynamics and sectoral statistics, we mapped nine ES across China from 2000 to 2020 at 1 km resolution. Results revealed pronounced ES supply and demand spatio-temporal heterogeneity. While the national ESF pattern remained stable, most services showed increasing exterior reliance, whereas water yield and tourism recreation became more locally sustained. Using flow balance and demand fulfillment as policy-proximal indicators, five management zones were delineated: local-sustained counties dominated southern China (∼30%); local-pressured types occurred in the Northeast, Qinghai-Tibet, and southwestern areas (∼15%); external-pressured types occurred in arid northwestern regions (1%-3%); southeastern coasts shifted toward external-sustained types (∼30%); and dynamic-transitional counties (∼20%) were scattered nationwide. By decomposing supply-demand relations into supply realization, spatial reallocation, and demand fulfillment, our framework helps align ecological functions with management priorities and offers insights for reconciling development and conservation in comparable socio-ecological contexts.

PMID:41984530 | DOI:10.1002/advs.202522070

JMIR Form Res. 2026 Apr 15;10:e88512. doi: 10.2196/88512.

ABSTRACT

BACKGROUND: The rapid evolution of digital technologies has transformed health, mental health, and social care, offering new modalities of digital care, assistance, and support through web-based platforms, mobile apps, extended reality, wearables, and artificial intelligence systems. Despite this proliferation, there is little consensus on what constitutes “high-quality” digital care. Challenges persist regarding data security, interoperability, accessibility, sustainability, and professional competence, whereas existing standards and regulations provide fragmented guidance.

OBJECTIVE: This study aimed to develop a contextualized, consensus-based quality assessment framework for digital care, assistance, and support in Flanders, Belgium. For this purpose, perspectives across technology, organizational processes, and professional competencies were integrated.

METHODS: The study used a multiphase design comprising (1) 10 expert interviews with Flemish government officials; (2) a narrative literature review of 303 peer-reviewed and gray literature sources; (3) a 3-round Delphi study with 50 experts across 5 domains (end users, facilitators, technology developers, deontology and ethics experts, and digital inclusion and media literacy experts); and (4) 4 complementary focus groups and 3 interviews with specialists in artificial intelligence, regulation, social work, mental health, and IT. The Delphi rounds gathered iterative feedback through open-ended elicitation, structured rating, and classification of quality criteria. Quantitative data were analyzed using descriptive statistics, whereas qualitative feedback was subjected to thematic analysis.

RESULTS: A total of 50 experts participated in round 1, a total of 40 (80%) participated in round 2, and 27 (54%) participated in round 3. Round 1 generated 577 unique quality criteria, consolidated into 26 clusters organized under 3 pillars: technology, organization, and professional competencies. The relative importance across pillars was balanced (mean score 37.29, SD 12.38 for technology; 33.33, SD 10.39 for professional competencies; and 29.80, SD 10.45 for organizations). Accessibility, reliability, and safety ranked highest for the technology; vision, quality monitoring, and infrastructure ranked highest for organization; and support, digital competencies, and ethics ranked highest for professional competencies. The finalized framework included 112 criteria, of which 35 (31.3%) were designated as optional and 77 (68.8%) were designated as minimum requirements. Focus groups and interviews validated the framework’s comprehensiveness and usability, emphasizing proportional implementation, user centrality, and alignment with European Union regulations. Stakeholders highlighted the need for tools, training, and governance mechanisms to ensure adoption and sustainability.

CONCLUSIONS: This study produced a codeveloped, context-sensitive quality assessment framework that balances technological robustness, organizational readiness, and professional competence in digital care, assistance, and support. The framework can serve both as a quality safeguard and a developmental road map. Accompanying self-assessment and governance tools enhance practical applicability. Implementation success will depend on governmental support, resource allocation, and structured feedback loops. Future research should pilot the framework in real-world settings, assess its impact, and establish mechanisms for continuous updates to maintain relevance in a rapidly evolving digital landscape.

PMID:41984529 | DOI:10.2196/88512

Orbit. 2026 Apr 15:1-5. doi: 10.1080/01676830.2026.2654185. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this project was to determine whether conjunctiva-shortening posterior approach ptosis repair affects the complication rates of subsequent bleb-forming glaucoma filtering surgeries compared to conjunctiva-sparing anterior approaches.

METHODS: A retrospective cohort study was conducted at the Cleveland Clinic Cole Eye Institute, including patients who underwent ptosis repair followed by glaucoma filtering surgery between January 2010 and December 2024. Patients were divided into anterior approach (levator advancement) and posterior approach (Müllerectomy with or without tarsectomy) groups. Outcomes included rates of intraoperative complications and postoperative bleb-related complications. Fisher’s exact test was used for group comparisons, with p ≤ 0.05 considered significant.

RESULTS: Thirty-five eyes (34 patients) were included: 17 underwent anterior and 18 underwent posterior approach ptosis repair. Intraoperative complications occurred in one eye in each group. Postoperative bleb-related complications were reported in two eyes in the anterior group and one in the posterior group. Rates of bleb-related complications were not statistically different between groups. Anterior approach eyes were more likely to have had prior glaucoma surgery and require repeat ptosis repair.

CONCLUSION: Prior posterior approach ptosis repair does not significantly increase the risk of intraoperative or postoperative bleb-related complications in subsequent glaucoma filtering surgery. These findings support the safety of posterior approach ptosis repair, even in patients likely to require future filtering procedures.

PMID:41984516 | DOI:10.1080/01676830.2026.2654185

J Vet Emerg Crit Care (San Antonio). 2026 Apr 15. doi: 10.1111/vec.70099. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine if the administration of 20% intravenous lipid emulsion (ILE) to healthy dogs at the standard antidotal dose induces a hypocoagulable state.

DESIGN: Prospective, nonblinded, crossover study.

SETTING: University teaching hospital.

ANIMALS: Twelve adult, purpose-bred Beagles with no history of recent illness or underlying endocrine disease.

INTERVENTIONS: Treated dogs received 20% ILE using a standard protocol for management of intoxications: 2 mL/kg bolus over 2 min, followed by 0.25 mL/kg/min for 60 min. Control dogs received lactated Ringer’s solution (LRS) using the same dosing scheme. Dogs were randomly assigned to receive ILE or LRS, then received the alternate treatment after a 1-week washout period.

MEASUREMENTS AND MAIN RESULTS: Viscoelastic coagulation monitoring parameters using a benchtop viscoelastic coagulation monitor, prothrombin time (PT), activated partial thromboplastic time, and platelet count were measured 5 min before and 5 min after interventions. Compared with LRS administration, there was an increase in clot formation time after ILE administration and a decrease in the alpha angle, amplitude at 10 min, and amplitude at 20 min. There was an increase in PT after LRS infusion. Otherwise, no differences were noted in PT, activated partial thromboplastic time, platelet counts, or remaining viscoelastic coagulation monitoring parameters for either group.

CONCLUSIONS: Viscoelastic findings were suggestive of a relative hypocoagulability after ILE administration. Although statistically significant, most of these values were still within the provided reference intervals, so the magnitude of change may not be clinically important. The increase in PT after LRS solution, while statistically significant, was clinically irrelevant. ILE was well tolerated at the antidotal dose and did not have a clinically relevant effect on coagulation in otherwise healthy dogs in this study.

PMID:41984515 | DOI:10.1111/vec.70099

Adv Sci (Weinh). 2026 Apr 15:e20580. doi: 10.1002/advs.202520580. Online ahead of print.

ABSTRACT

Glomerular pathology is central to the diagnosis and prognosis of renal diseases, yet the heterogeneity of glomerular morphology and fine-grained lesion patterns remain challenging for current AI approaches. We present GloPath, an entity-centric foundation model trained on over one million glomeruli extracted from 14 049 renal biopsy specimens using multi-scale and multi-view self-supervised learning. GloPath addresses two major challenges in nephropathology: glomerular lesion assessment and clinicopathological insights discovery. For lesion assessment, GloPath was benchmarked across three independent cohorts on 52 tasks-including lesion recognition, grading, few-shot classification, and cross-modality diagnosis-outperforming state-of-the-art methods in 42 tasks (80.8%). In the large-scale real-world study, it achieved an ROC-AUC of 91.51% for lesion recognition, demonstrating strong robustness in routine clinical settings. For clinicopathological insights, GloPath systematically revealed statistically significant associations between glomerular morphological parameters and clinical indicators across 224 morphology-clinical variable pairs, demonstrating its capacity to connect tissue-level pathology with patient-level outcomes. Together, these results position GloPath as a scalable and interpretable platform for glomerular lesion assessment and clinicopathological discovery, representing a step toward clinically translatable AI in renal pathology.

PMID:41984508 | DOI:10.1002/advs.202520580