Category: Statistics

Subst Abuse Treat Prev Policy. 2026 Jul 29;21(1):54. doi: 10.1186/s13011-026-00752-3.

ABSTRACT

BACKGROUND: The interrelationship between unemployment and substance use disorders, especially opioid use disorders, is complex, and basic epidemiological data are lacking both in Germany and elsewhere. This study aimed to evaluate the prevalence rates of opioid use disorder, work ability, and associated factors among unemployed individuals with opioid use disorder who underwent socio-medical assessment by the Medical Service (MS) of the Federal Employment Agency (FEA).

METHODS: All socio-medical assessments conducted between 2016 and 2021 (N = 4,249,028) were extracted from the FEA database and analyzed with respect to relevant sociodemographic characteristics, opioid use disorder (ICD-10 F11.x diagnosis) and work ability. Descriptive statistics were used to summarize the data.

RESULTS: A total of 4,249,028 unemployed individuals were assessed. Of these, 22,683 clients (0.5%) met an F11.x diagnosis (primary or secondary); mostly opioid dependence (N = 20,506; 94.3%). The number of diagnoses increased over time (2016-2021). Mean age was 40.7 ± 9.4 years. Overall, 15,065 (73.5%) were male and 5,441 (26.5%) were female. For individuals with a secondary diagnosis of F11.x, most frequent psychiatric comorbidities were alcohol dependence (27.8%), polysubstance use (17.6%), schizophrenia (8.8%), depression episode (8.3%) or recurrent depression (5.9%) and persistent pain disorder (6.1%). Regarding daily work capacity, 58.3% (n = 11,962) of individuals were able to work less than 3 h per day, 10.0% (n = 2,051) were able to work 3-6 h per day, and 17.4% (n = 3,568) were able to work more than 6 h per day.

CONCLUSIONS: The number of unemployed individuals with opioid dependence in Germany has increased over time, and most are unable to work more than three hours per day. The most frequent psychiatric comorbidities were other substance use disorders, particularly alcohol use disorder, schizophrenia, and depression. Somatic comorbidities, with the exception of chronic viral hepatitis, were recorded less frequently. Tailored interventions and closer collaboration between employment agencies and mental health care providers are needed to improve the psychosocial integration of this population.

PMID:42538530 | DOI:10.1186/s13011-026-00752-3

Respir Res. 2026 Jul 28;27(1):296. doi: 10.1186/s12931-026-03843-8.

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by right ventricular (RV) pressure overload, dilatation and dysfunction, which are key prognostic determinants. While riociguat improves exercise capacity and hemodynamics, prospective data on reverse remodeling remain limited. This prospective, phase IV study evaluated the effects of riociguat on right-heart size, function, hemodynamics, exercise capacity and safety in PAH patients.

METHODS: Treatment-naïve or pretreated PAH patients were enrolled. Patients receiving phosphodiesterase-5 inhibitors (PDE5i) could be switched to riociguat upon clinical indication. The primary endpoint was the change in right atrial (RA) and RV area at 24 weeks. Secondary endpoints included additional echocardiographic, clinical, exercise, hemodynamic and laboratory parameters, as well as quality-of-life (QoL) and safety.

RESULTS: Thirty patients (61.2 ± 14.5 years; 76.7% male; 24 PDE5i-pretreated) were enrolled. Marked right-heart dilatation and impaired RV function were prominent at baseline. At week 24, riociguat significantly reduced RA (Δ -3.17 ± 5.91 cm²; p = 0.006) and RV area (Δ -6.00 ± 3.80 cm²; p < 0.0001). Furthermore, RV-fractional area change, 6-minute walking distance and functional class improved significantly. In patients with invasive follow-up, cardiac index increased significantly, with favorable trends in further parameters. N-terminal pro-brain natriuretic peptide and QoL remained unchanged. The study terminated early following the decision by the supplier Merck/MSD; the termination was not safety related. Riociguat was generally well tolerated with no new safety concerns.

CONCLUSION: Riociguat therapy resulted in a statistically significant improvement in right ventricular and atrial size and function with further improvements in exercise capacity and functional class. This prospective trial confirms the findings of previous retrospective studies and supports riociguat as an effective treatment option to improve RV geometry and performance.

TRIAL REGISTRATION: This trial was registered on clinicaltrials.gov with the ClinicalTrials.gov ID NCT04954742.

PMID:42538528 | DOI:10.1186/s12931-026-03843-8

Stat Med. 2026 Aug;45(18-19):e70685. doi: 10.1002/sim.70685.

ABSTRACT

The illness-death model is widely used to characterize disease progression over time. Previous work focuses either on estimation without causal interpretation or on causal interpretation under a strong Markov assumption where the terminal event depends on the status but not the timing of the intermediate event. To bridge the research gap, we propose a new definition of counterfactual hazard that relaxes the Markov assumption by considering the entire history of the intermediate event. We derive an identification formula that involves an integral with respect to the probability density function of the intermediate event time. Direct and indirect effects refer to the influence of an exposure on the terminal event not mediated by, and mediated through, the intermediate event, respectively. We propose non-parametric kernel estimators for the two effects and study their asymptotic properties. We conduct numerical simulations to examine the proposed estimators’ finite-sample performance. Applying the method to a hepatitis study where the Markov assumption is violated, we show that the effect of hepatitis C on mortality is not mediated through septicemia during the first 15 years of follow-up.

PMID:42538523 | DOI:10.1002/sim.70685

Drugs Real World Outcomes. 2026 Jul 31. doi: 10.1007/s40801-026-00574-6. Online ahead of print.

ABSTRACT

BACKGROUND: Dotinurad, a novel selective uric acid (UA) reabsorption inhibitor, exerts its hypouricemic effect through the selective inhibition of urate transporter 1 (URAT1). The present study aimed to investigate the short-term effectiveness and safety of dotinurad in the treatment of Chinese patients with gout, while also conducting a comparative analysis with febuxostat.

METHODS: This retrospective study enrolled 70 consecutive eligible inpatients and outpatients with gout from the Department of Rheumatology and Immunology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, were screened during the period from 1 January 2025 to 30 December 2025. Treatment was prescribed at the discretion of the treating clinician: 35 patients receiving dotinurad and 35 receiving febuxostat. The primary analyses focused on serum uric acid (UA) target attainment (≤ 360 μmol/L or ≤ 300 μmol/L) for patients with dotinurad or febuxostat) and short-term urate-lowering effectiveness after 4 weeks of treatment. Short-term changes in hepatic and renal function parameters were also evaluated.

RESULTS: After one month of treatment, the attainment rates for UA ≤ 360 μmol/L in the dotinurad group and the febuxostat group were 60.0% and 45.7%, respectively. The attainment rates for UA ≤ 300 μmol/L were 45.7% and 14.3%, respectively. While baseline UA levels did not differ significantly between the two groups (P = 0.227), a significant difference was observed after 4 weeks of treatment (The serum UA levels at week-4 after treatment in the dotinurad group and febuxostat group were 294.47 ± 19.31 and 380.85 ± 21.43, respectively; P = 0.003). After one month of treatment, significant intergroup differences were observed in the changes from baseline of UA and serum creatinine (SCR) (P = 0.003 and P = 0.029, respectively), whereas no statistically significant intergroup differences were found in the changes from baseline of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P = 0.761 and P = 0.551, respectively).

CONCLUSIONS: It was found that 2 mg/day of Dotinurad was superior to 40 mg/day of febuxostat in achieving serum UA levels ≤ 360 μmol/L or ≤ 300 μmol/L after 4 weeks in Chinese patients with gout and exerted superior short-term urate-lowering effectiveness to febuxostat. Additionally, dotinurad is not associated with a risk of hepatic or renal injury in the short term, whereas febuxostat may increase SCR levels over the short course. The conclusions are only applicable to the clinical medication setting where febuxostat is initiated at a dose of 40 mg in Chinese patients with gout.

PMID:42538516 | DOI:10.1007/s40801-026-00574-6

World J Microbiol Biotechnol. 2026 Jul 31;42(8):441. doi: 10.1007/s11274-026-05172-w.

ABSTRACT

Hospital-wide cumulative antibiograms guide empirical therapy but may conceal clinically relevant resistance heterogeneity across inpatient settings. We conducted a retrospective, single-center study of inpatient antimicrobial susceptibility testing (AST) data collected at a Chinese tertiary hospital from 2019 to 2025. For each patient, the first isolate of each organism in each calendar year was selected and its complete AST panel retained. The primary comparison was between adult intensive care unit (ICU) wards and all other inpatient wards. Temporal trends were assessed using the conventional Cochran-Armitage test with false discovery rate correction, and sensitivity analyses excluded hospital-based SARS-CoV-2 high-activity periods. The analysis included 45,645 index isolates from 26,297 patients. Meropenem resistance among Acinetobacter baumannii isolates was 90.7% in adult ICU wards versus 61.9% in non-ICU wards. Corresponding ICU versus non-ICU percentages were 35.5% versus 20.4% for imipenem-resistant Pseudomonas aeruginosa, 57.0% versus 47.0% for oxacillin-resistant Staphylococcus aureus, and 34.7% versus 17.2% for imipenem-resistant Klebsiella pneumoniae. Hospital-wide percentages were lower than the corresponding adult ICU percentages. Carbapenem-resistant A. baumannii and K. pneumoniae declined after false discovery rate correction, whereas methicillin-resistant S. aureus, carbapenem-resistant P. aeruginosa, and levofloxacin-resistant Escherichia coli showed no robust temporal trends. Excluding SARS-CoV-2 high-activity periods did not materially change the main findings. Care-setting-stratified cumulative antibiograms identified resistance heterogeneity not apparent from hospital-wide summaries and may complement hospital-wide reporting for local empirical therapy and stewardship guidance.

PMID:42538493 | DOI:10.1007/s11274-026-05172-w

Nat Methods. 2026 Jul 31. doi: 10.1038/s41592-026-03187-7. Online ahead of print.

NO ABSTRACT

PMID:42538469 | DOI:10.1038/s41592-026-03187-7

Nat Methods. 2026 Jul 31. doi: 10.1038/s41592-026-03140-8. Online ahead of print.

ABSTRACT

Spatially resolved multimodal data enable the exploration of transcriptional, proteomic and metabolic regulation, yet analytical tools to integrate these spatial omics modalities, particularly spatial metabolomics, remain limited. We developed SpaMTP, an end-to-end framework that implements functions within a common Seurat architecture. It introduces analyses for metabolite annotation, joint clustering, enrichment tests, spatial alignment, multimodal integration, visualization and seamless software interoperability. Its utility is demonstrated across different biological systems.

PMID:42538468 | DOI:10.1038/s41592-026-03140-8

Environ Sci Pollut Res Int. 2026 Aug 1. doi: 10.1007/s11356-026-38089-w. Online ahead of print.

ABSTRACT

Air pollution is a well-established risk factor for physical illness and premature mortality, yet its relationship with suicide remains less well understood, particularly at the national level and over longer periods of exposure. Although previous studies have reported positive associations between particulate matter and suicide, evidence remains heterogeneous, and national longitudinal analyses are limited. This study examines the association between fine particulate matter (PM₂.₅) concentrations and suicide mortality across local authorities in the UK between 2015 and 2023. Suicide data obtained from the UK Office for National Statistics were combined with modelled PM₂.₅ estimates from the Department for Environment, Food and Rural Affairs, resulting in a balanced panel of more than 2200 local authority-year observations. Fixed-effects panel regression models were employed to account for unobserved time-invariant local characteristics and common year-specific shocks, while nonlinear specifications were estimated to examine potential threshold effects. The descriptive analysis revealed a negative cross-sectional association between PM₂.₅ concentrations and suicide rates. However, after controlling for local authority and year fixed effects, PM₂.₅ was positively and significantly associated with suicide mortality (β = 0.221, p = 0.007). The nonlinear model further identified a statistically significant U-shaped relationship, with an estimated turning point at approximately 7.8 µg/m³, suggesting that higher PM₂.₅ concentrations are associated with increased suicide mortality beyond this threshold. Although the nonlinear specification modestly improved model fit, the findings should be interpreted cautiously given the observational design and the absence of certain time-varying socioeconomic controls. Overall, the results suggest that the relationship between PM₂.₅ and suicide mortality is conditional rather than uniform, varying across pollution exposure levels and geographic contexts. While the findings provide national-scale evidence on the association between long-term PM₂.₅ exposure and suicide mortality in the UK, they should be interpreted as exploratory associations rather than evidence of causality. Future research incorporating additional socioeconomic variables, longer time series, and higher temporal resolution data is needed to further evaluate these relationships.

PMID:42538457 | DOI:10.1007/s11356-026-38089-w

Nat Comput Sci. 2026 Jul 31. doi: 10.1038/s43588-026-01030-9. Online ahead of print.

ABSTRACT

Single-cell sequencing has transformed our understanding of cellular heterogeneity, enabling the construction of multi-omics atlases through data integration. However, conventional atlas updates require full reintegration of all datasets, creating scalability challenges that limit the timeliness and adaptability of biomedical research. Here we present multimodal integration with continual learning (MIRACLE), an online learning framework for scalable multimodal integration. Using dynamic architecture adaptation and data rehearsal, MIRACLE continually integrates diverse datasets while preserving biological fidelity. Across evaluations, MIRACLE achieves accurate online integration with substantially improved efficiency, refining and expanding atlases with new cross-modal, cross-tissue and cross-disease data. Applied to respiratory infections, it reveals both shared and pathogen-specific immune mechanisms in coronavirus disease 2019, influenza A and tuberculosis. Overall, MIRACLE provides an efficient and collaborative solution for the continual integration, sharing and exploration of biological knowledge.

PMID:42538449 | DOI:10.1038/s43588-026-01030-9

Nat Med. 2026 Jul 31. doi: 10.1038/s41591-026-04521-4. Online ahead of print.

ABSTRACT

Recent rapid progress in the field of computational pathology has been enabled by foundation models. These models are beginning to move beyond encoding image patches toward whole-slide understanding, but their clinical utility remains limited. Here we present PRISM2, a multimodal slide-level foundation model trained on 2.3 million whole-slide images and 14 million question-answer pairs derived from 700,000 pathology reports. Through clinical dialogue supervision, PRISM2 aligns histomorphology with diagnostic reasoning, yielding representations that support both prompt-based inference and transferable embeddings for downstream tasks. With prompt-based inference, PRISM2 achieves or exceeds (P < 0.05) the balanced accuracy of clinical-grade products calibrated for cancer detection in the prostate, breast and breast lymph node. Additionally, across comprehensive diagnostic, biomarker and survival benchmarks, PRISM2 embeddings never statistically underperform previous foundation models via linear probing (P < 0.05). Furthermore, task-specific fine-tuning on survival prediction outperforms training from scratch on the same large survival dataset. PRISM2 demonstrates how language-supervised pretraining provides a scalable, clinically grounded signal for generalizable pathology representations, bridging human diagnostic reasoning and foundation model performance.

PMID:42538427 | DOI:10.1038/s41591-026-04521-4