Tag: statistics

Nucleic Acids Res. 2026 May 5;54(9):gkag466. doi: 10.1093/nar/gkag466.

ABSTRACT

Spatial transcriptomics (ST) unlocks potential for studying gene functions in processes that depend on orchestration of transcription across space. However, analysis tools for ST remain aimed at data exploration, with few resources for hypothesis testing. What’s missing is a way to test whether a factor of interest affects functionally relevant parameters of a gene’s spatial distribution. We present a tool to fill this gap, which we call a warped sigmoidal Poisson-process mixed-effects (WSP, pronounced “wisp”) model. WSP models are the first ST tool allowing researchers to test critical questions without bespoke preprocessing pipelines for identifying key spatial parameters. By aligning coordinates to an axis of interest and letting a likelihood-based regression find between-group effects on expression rates and boundaries, WSP models replace error-prone manual preprocessing with minimally biased hypothesis testing. After introducing WSP models, we demonstrate their statistical validity using semi-synthetic simulated data and their ability to test for effects by applying them to MERFISH data from mouse somatosensory cortex and bulk sequencing data from mouse liver lobules with extrapolated spatial coordinates. Together, these validations and applications demonstrate that WSP models offer a practical and statistically rigorous approach to quantifying and testing for effects on spatial variation in transcriptomic data.

PMID:42137981 | DOI:10.1093/nar/gkag466

Palliat Support Care. 2026 May 15;24:e146. doi: 10.1017/S1478951526102247.

ABSTRACT

INTRODUCTION: Depression in cancer patients is a common condition that poses significant challenges for prognosis, treatment adherence, and quality of life. Its onset reflects the interplay of diverse biological, psychological, and social factors, which has been the focus of numerous studies.

METHODS: We identified both systematic and non-systematic reviews examining cross-sectional or prospective studies reporting associations between DAFs and depression. We extracted data relative to DAFs, as well as the direction and statistical significance of the reported association. Consistency of findings was assessed by estimating the proportion of concordant studies (PCS) for each DAF. Methodological quality and risk of bias were assessed using a standardized tool.

RESULTS: We identified 73 reviews (26 systematic and/or meta-analyses, 47 narrative) encompassing 514 unique primary studies, reporting the associations between depression and 198 distinct DAFs. DAFs were grouped into six domains (sociodemographic, cancer-related, somatic, psychological, biological-genetic, and other). The strongest associations (PCS ≥ 75% and ≥5 studies) were observed for sociodemographic factors (e.g., high social support, being unmarried), inflammatory markers (IL-6, TNF-α, CRP), psychological factors (e.g., history of depression, distress, anxiety), and somatic factors (e.g., fatigue, low functional status, malnutrition). When restricting analyses to prospective studies, consistent associations emerged for cancer-related physical symptoms and time dedicated to patient communication.

CONCLUSIONS: Depression in cancer is multifactorial, with physical and psychosocial factors likely iteracting dynamically. Prospective studies are still greatly needed. Further research on risk and protective factors may facilitate risk stratification, early diagnosis and patient management.

PMID:42137975 | DOI:10.1017/S1478951526102247

Health Serv Res. 2026 Jun;61(3):e70121. doi: 10.1111/1475-6773.70121.

ABSTRACT

OBJECTIVE: To evaluate whether payment reductions achieved during the Oncology Care Model (OCM) continued after the model ended.

STUDY SETTING AND DESIGN: OCM was a voluntary episode-based alternative payment model designed to improve the value of care for Medicare beneficiaries receiving chemotherapy for cancer. Participating practices received $160 monthly care coordination payments and could receive shared savings (or penalties) according to quality and spending goals during 6-month episodes. We extended the OCM regression-adjusted difference-in-differences (DID) payment analysis by 18 months after the model’s conclusion to assess sustained effects on total episode payments (TEP) and component Parts A, B, and D, and Part B drug payments.

DATA SOURCES AND ANALYTIC SAMPLE: We used Medicare administrative data, model program data, and secondary sources describing market and provider characteristics to analyze 6-month chemotherapy episodes for Medicare fee-for-service beneficiaries initiated during January 2014-July 2015 (baseline), July 2016-December 2021 (performance), and January 2022-June 2023 (post-performance).

PRINCIPAL FINDINGS: In the 18 months following OCM’s end, on average, OCM practices reduced TEP by -$955, driven by significant reductions in Part B payments (-$559). Part B payment reductions were primarily for non-chemotherapy drugs (-$489). Overall payment reductions totaled $328 million. Sustained payment reductions were predominantly among practices adopting two-sided risk; these practices reduced TEP by $3379, including significant reductions in Parts A (-$738), B (-$1370), and D (-$1112) payments.

CONCLUSION: OCM savings following the model’s end were driven by practices that adopted two-sided risk. These sustained payment reductions after OCM’s conclusion provided substantial additional savings for CMS, reducing estimated model losses from $639 million to $311 million.

PMID:42137948 | DOI:10.1111/1475-6773.70121

Int J Biostat. 2026 May 15. doi: 10.1515/ijb-2024-0034. Online ahead of print.

ABSTRACT

The prognostic score (PGS) is a function of observed covariates that summarizes covariates’ association with potential responses. In the current study, we propose a full prognostic score (FPGS), an extension of the PGS that integrates individual prognostic scores to account for confounding adjustments in causal inference. Under effect modification, we show that FPGS and a version of FPGS using conditional expectations of the outcomes, meet the sufficiency condition for confounding adjustment to estimate the average causal effect. We present a general algorithm to implement the FPGS approach for estimation by applying linear regression, random forest regression, and XGBoost regression. When determining the average causal effect, we incorporate FPGS into semiparametric estimators including regression imputation, simple stratification, and targeted maximum likelihood estimation (TMLE). The finite-sample properties of the estimators are compared through three simulation studies. Based on the findings of the FPGS estimators, the mean squared error of the linear regression imputation estimator and the TMLE estimator comprised of linearly regressed PGS is smaller than the mean squared error of alternative estimators. In an empirical study, we analyze data from the National Health and Nutrition Examination Survey (NHANES, 2007-2008) to determine the effect of smoking on blood lead levels.

PMID:42137947 | DOI:10.1515/ijb-2024-0034

Health Serv Res. 2026 Jun;61(3):e70130. doi: 10.1111/1475-6773.70130.

ABSTRACT

OBJECTIVE: To examine whether different caregiving arrangements influence hospitalization risk and frequency among older adults with functional limitations.

STUDY SETTING AND DESIGN: This longitudinal study used linear probability and Poisson regression models with individual and wave fixed effects, lagged predictors, and household-clustered standard errors to assess associations between different caregiving arrangements and hospitalization outcomes among community-dwelling older adults in the United States. Caregiving was categorized as no help, family help, formal help, or combined help. Outcomes included any hospitalization and the number of hospital stays over a two-year period.

DATA SOURCES AND ANALYTIC SAMPLE: Data came from eight waves of the Health and Retirement Study (2004-2018). The samples included adults aged 65 and older who reported difficulty with at least one activity of daily living and participated in at least two survey waves. The final analytic sample comprised 2926 individuals contributing 5595 person-wave observations.

PRINCIPAL FINDINGS: While the overall hospitalization risk did not differ significantly by caregiving type, receiving combined support was associated with a reduced number of hospital stays among those hospitalized (IRR = 0.712, p < 0.01), compared to receiving no support. Cognitive functioning modified these relationships, with formal help linked to fewer hospitalizations among those with impairment but more among those without. Differences also emerged across racial and ethnic groups, where formal help was linked to lower hospitalization rates for Black individuals, and combined help was associated with increased hospitalizations among Hispanic older adults.

CONCLUSIONS: Policies that expand access to both formal and family caregiving support may help reduce hospitalizations among older adults with functional limitations, particularly when tailored to care recipient characteristics.

PMID:42137944 | DOI:10.1111/1475-6773.70130

Clin Toxicol (Phila). 2026 May 15:1-8. doi: 10.1080/15563650.2026.2661378. Online ahead of print.

ABSTRACT

INTRODUCTION: Poison information centres advise health professionals on toxic exposures and recommend appropriate responses, preventing transfer where hospital treatment is not required. No study to date has detailed ambulance enquiries for poison information in Great Britain. The aim of this study is to describe ambulance services’ use of the National Poison Information Service through helpline calls and TOXBASE^® accesses.

METHODS: Retrospective records analysis of ambulance calls and TOXBASE^® accesses between 1 April 2022 and 31 March 2023 in England, Scotland, and Wales. The data were analysed descriptively with frequency statistics calculated for patient demographics, characteristics of the poisoning, and advice for transfer to onward care.

RESULTS: There were 4,053 ambulance enquiries, representing 11.0% of calls. The rate of calls per 100,000 population was 6.9 for English, 3.2 for Welsh, and 0.4 for Scottish ambulance services. Conversely, the rate of TOXBASE^® accesses was 369.2 per 100,000 for English, 233.9 for Scottish, and 111.9 for Welsh ambulance services. Phone enquiries were mostly for intentional poisoning (2342/4053 [57.8%]) involving pharmaceuticals (3502/4053 [86.4%]). Most enquiries were benign exposures at the time of the call; Poisoning Severity Score None or asymptomatic (2256/4053[55.7%]) or Minor (1536/4053[37.9%]). Most calls resulted in advice for patient transfer to definitive care (3114/4053, 76.8%). For calls and TOXBASE^® accesses, the most common agent was paracetamol.

DISCUSSION: Ambulance services in Great Britain commonly seek poison information to inform patient management by phone and TOXBASE^®. Calls primarily relate to intentional poisoning with advice to transfer to further care. Yet, for a quarter of cases no further care is advised which likely has a cost-saving effect. Further research is needed to explore how and when paramedics seek poison information.

CONCLUSIONS: These data emphasise the importance of ensuring poisons management advice is tuned to ambulance services’ needs to ensure appropriate management and patient transfer.

PMID:42137929 | DOI:10.1080/15563650.2026.2661378

EuroIntervention. 2026 May 15;22(10):545-554. doi: 10.4244/EIJ-D-26-00032.

ABSTRACT

BACKGROUND: Despite the growing demand for transcatheter aortic valve implantation (TAVI), there is no strategy to prevent its most common complication: cardiac conduction disturbances (CCD). These disturbances often necessitate permanent pacemaker implantation (PPI), leading to high morbidity and costs. Post-TAVI CCD may be transient, resulting from inflammation.

AIMS: We aimed to evaluate the feasibility, safety, and preliminary efficacy of glucocorticoids in preventing PPI in patients undergoing TAVI.

METHODS: This pilot study followed a Prospective Randomised Open-label Blinded Endpoint (PROBE) design. One hundred TAVI patients were randomised 1:1 to standard care or methylprednisolone (7 mg/kg administered 1 hour preprocedure), followed by prednisone (15 mg every 12 hours for 5 days). Electrocardiograms and inflammatory biomarkers were assessed pre- and post-intervention, and at 1 month and 1 year. The primary efficacy endpoint was the 1-month incidence of PPI. Secondary outcomes included 1-year PPI, new left bundle branch block (LBBB), LBBB and PPI, other CCD, mortality, and procedural complications.

RESULTS: The primary efficacy outcome occurred in 16% of the control group and 8% of the intervention group, reflecting a 50% relative risk (RR) reduction in PPI (RR 0.50, 95% confidence interval [CI]: 0.16-1.55; p=0.23). There was no significant difference in 1-year PPI (RR 0.67, 95% CI: 0.26-1.73; p=0.41) or new LBBB (RR 1.12, 95% CI: 0.66-1.89; p=0.66). The intervention was safe, without differences in complications, mortality (4% vs 12%; p=0.27), or adverse events (n=3).

CONCLUSIONS: Glucocorticoids in TAVI are feasible and safe. The observed numerical difference in PPI did not reach statistical significance. Large-scale trials are needed to confirm the results of this pilot study.

PMID:42137921 | DOI:10.4244/EIJ-D-26-00032

EuroIntervention. 2026 May 15;22(10):566-574. doi: 10.4244/EIJ-D-25-01337.

ABSTRACT

BACKGROUND: Dedicated randomised studies on intravascular imaging guidance in unprotected left main coronary artery (LMCA) disease are lacking.

AIMS: We aimed to investigate the clinical feasibility of optical coherence tomography (OCT) guidance in percutaneous coronary intervention (PCI) of true LMCA bifurcation lesions and to evaluate its prognostic impact compared with angiographic guidance.

METHODS: Patients with true LMCA bifurcation lesions who were randomised to either OCT or angiographic guidance in the OCTOBER Trial were included. The feasibility of OCT guidance was assessed as the proportion of patients with successful and analysable OCT pullbacks before, during, and after stenting. Clinical outcomes between the two groups were compared based on the incidence of a composite of major adverse cardiac events (MACE), comprising cardiac death, any myocardial infarction, or target lesion revascularisation.

RESULTS: In total, 227 patients were included (OCT: 111, angiography: 116). OCT guidance was successful, with 98% of cases having a pre-stenting pullback performed and 96% a final pullback, as per protocol. The proximal LMCA stent edge was analysable in 43% of patients, and in the remaining 57%, only 5% were limited by insufficient image quality. No statistically significant difference in MACE was observed between the two groups (OCT: 14.4% vs angiography: 18.4%, hazard ratio 0.78, 95% confidence interval: 0.39-1.51).

CONCLUSIONS: OCT-guided PCI in true LMCA bifurcation lesions was clinically feasible, but visibility of the LMCA ostium was limited by short pullbacks, insufficient clearance, or guide catheter shadowing. OCT guidance was associated with a non-significant reduction in MACE, consistent with the effect estimate in the main trial.

PMID:42137920 | DOI:10.4244/EIJ-D-25-01337

BJOG. 2026 May 15. doi: 10.1111/1471-0528.70260. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare Vaginal Hysterectomy (VH) with Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) hysterectomy (VANH) as a day-care procedure.

DESIGN: Single-blind, multicentre randomised controlled trial.

SETTING: Two Dutch non-academic teaching hospitals.

POPULATION: Women aged ≥ 18 years undergoing hysterectomy for benign indications.

METHODS: Women were randomised 1:2 (VH or VANH). Primary outcome was SDD. Secondary outcomes included operative time, rate of elective salpingectomies, intraoperative blood loss, complications (Clavien-Dindo), pain scores (NRS) and analgesic use, post-operative recovery (RI-10), and quality of life (EQ-5D-5L). Analyses were performed on an intention-to-treat basis.

RESULTS: A total of 113 patients were included in the analyses (n = 42 VH, and n = 71 VANH). SDD occurred significantly more frequently in the VANH group (87.3%) than VH group (71.4%; OR 2.76, 95% CI 1.04-7.25; p = 0.04). VANH was associated with a significantly shorter operative time (median 55 min versus 65 min; p = 0.005), less blood loss (median 50 mL vs. 150 mL; p < 0.001) and more often elective opportunistic salpingectomy compared to VH (100% vs. 77.4%; p = 0.008). NRS were significantly lower in the VANH group the first hour post-operative (3 vs. 1, p < 0.001). Post-operative complications (VH 9.5% vs. VANH 15.5%; p = 0.34), readmission (VH 4.8% vs. VANH 8.5%; p = 0.47), analgesic use, recovery, and quality of life were not statistically significant.

CONCLUSIONS: VANH is a safe and effective alternative to VH, offering a higher likelihood of SDD, shorter operative time, reduced blood loss, and more often an elective salpingectomy, without increased complications or differences in pain, recovery, or quality of life.

PMID:42137913 | DOI:10.1111/1471-0528.70260

Nat Ment Health. 2026;4(5):792-805. doi: 10.1038/s44220-026-00623-7. Epub 2026 Apr 21.

ABSTRACT

Autism is a heterogeneous condition, and functional magnetic resonance imaging-based studies have advanced understanding of neurobiological correlates of autistic features. Little work has focused on the optimal brain states to reveal brain-phenotype relationships. Here, using connectome-based predictive modeling, we interrogated four datasets to determine scanning conditions that boost prediction of clinically relevant phenotypes and assess generalizability. In dataset one, a sample of youth with autism and neurotypical participants (n = 63), we found that a sustained attention task resulted in high prediction performance of autistic traits compared with a free-viewing social attention task and a resting-state condition. In dataset two (n = 25), we observed the predictive network model of autistic traits generated from the sustained attention task generalized to predict measures of attention in neurotypical adults. In datasets three and four, we determined the same predictive network model further generalized to predict measures of social responsiveness in the Autism Brain Imaging Data Exchange (n = 229) and the Healthy Brain Network (n = 643). Our data suggest an in-scanner sustained attention challenge can help delineate robust markers of autistic traits.

PMID:42137910 | PMC:PMC13167459 | DOI:10.1038/s44220-026-00623-7