Category: Statistics

Cardiooncology. 2026 Jul 30;12(1):103. doi: 10.1186/s40959-026-00544-5.

ABSTRACT

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has substantially improved outcomes in refractory hematologic malignancies but may cause cardiovascular complications, particularly in the context of cytokine release syndrome (CRS). Real-world data on incidence, severity, and prognostic relevance of cancer therapy-related cardiovascular toxicity (CTR-CVT) defined by the 2022 ESC cardio-oncology guidelines remain in the context of CAR-T cell therapy limited.

METHODS: This retrospective single-center study includes 104 patients treated with CAR T-cells between 09/2019 and 02/2024 for acute lymphoblastic leukemia, non-Hodgkin lymphoma and multiple myeloma. The primary endpoint was new-onset CTR-CVT during hospital stay, defined as cancer therapy-related cardiac dysfunction (CTRCD), arrhythmia, myocardial infarction, cardiogenic shock, or cardiovascular death. Clinical characteristics, biomarkers, echocardiographic parameters, CRS/ICANS severity, and survival outcomes were analyzed.

RESULTS: Fifty-two patients (50%) met criteria for CTR-CVT, predominantly due to asymptomatic biomarker elevation. CTRCD occurred in 48.1%, whereas clinically significant events were rare: three patients developed symptomatic CTRCD, one experienced cardiogenic shock, and no myocardial infarctions or cardiovascular deaths were observed. Cardiovascular events occurred early and were associated with higher-grade CRS and ICANS, as well as elevated inflammatory markers. Reduced baseline left ventricular ejection fraction, elevated systolic pulmonary artery pressure, impaired performance status, and beta-blocker use were associated with increased CTR-CVT risk. Survival was numerically lower in patients with CTR-CVT but did not reach statistical significance.

CONCLUSION: Although half of patients fulfilled ESC criteria for CTR-CVT, clinically relevant cardiac events after CAR T-cell therapy were uncommon. These findings suggest potential overclassification driven by biomarker elevations and underscore the importance of emphasizing clinical relevance when assessing cardiotoxicity in CAR T-cell recipients.

PMID:42538564 | DOI:10.1186/s40959-026-00544-5

Fluids Barriers CNS. 2026 Jul 31;23(1):93. doi: 10.1186/s12987-026-00831-4.

ABSTRACT

Using adeno-associated virus to transfer genetic information to the choroid plexus has emerged as a promising route for long-term gene therapy in the brain for a variety of conditions. Overexpression of proteins has proved effective in small animal models but few attempts have been made to translate this technology to clinic, suppress the activity of a protein of interest, or further expand the limited capsid serotypes known to have choroid plexus tropism. We utilise transfer of green fluorescent protein to show choroid plexus epithelium tropism for novel AAV6 derived capsid ShH10^Y445F in mouse, rat and porcine tissue explant cultures. In vivo tropism is shown in the mouse following stereotactic intracerebroventricular injection. We examined the distribution of viral transduction across the choroid plexus in all four ventricles following a single unilateral intracerebroventricular injection using both green fluorescent protein as a transgene, but also the CRISPR/Cas9 system to deliver permanent knockdown of apical water channel aquaporin-1. Quantitative immunofluorescence and SURVEYOR assay were used to statistically assess the magnitude and extent of choroid plexus knockdown across the ventricular system. We conclude that serotype ShH10^Y445F targets choroid plexus epithelium in mouse, rat and pig; and when carrying the CRISPR/Cas9 system can reduce target protein expression in these cells. Transduced choroid plexus epithelial cells distribute unevenly with a bias toward the lateral ventricle on the injected side and a preferential infection of choroid plexus in the lateral over the third and fourth ventricles. Overcoming irregular distribution represents a challenge for clinical translation of this technology where clinical efficacy may require manipulation of the entire choroid plexus.

PMID:42538560 | DOI:10.1186/s12987-026-00831-4

J Biomed Semantics. 2026 Jul 27;17(1):14. doi: 10.1186/s13326-026-00364-7.

ABSTRACT

BACKGROUND: Phenotyping, the comprehensive assessment of observable characteristics, is essential for advancing medical understanding and personalised healthcare. However, traditional phenotyping methods are often manual, time-intensive, and limited in scope. To address these challenges, this work introduces the TOP Framework, a software suite that leverages a structured approach. It provides tools for the formal definition of phenotypes, their organisation into ontological classes, the creation of phenotype models for disease-specific knowledge representation, and the generation of phenotype queries for automated data retrieval and analysis. A dynamic phenotype algorithm integrates these modules to efficiently identify individuals meeting complex phenotypic criteria. The Model for End-Stage Liver Disease (MELD) score serves as a running example to illustrate the framework’s capabilities. Furthermore, this paper presents a preliminary evaluation of the TOP Framework’s user experience by means of the User Experience Questionnaire (UEQ), assessing its usability and suitability for researchers and clinicians.

RESULTS: The TOP Framework includes a robust implementation of a reasoner model for deriving complex phenotypes and an automated testing module to ensure reliability. The user experience evaluation yielded generally positive results on a scale from -3 to 3 (n = 11), with mean scores and 95% confidence intervals as follows: attractiveness, 1.50 (CI = (1.07, 1.93)); pragmatic quality, 1.38 (CI = (1.00, 1.77)); and hedonic quality, 1.40 (CI = (0.76, 2.03)).

CONCLUSIONS: The TOP Framework offers a novel and automated approach to phenotyping, with the potential to enhance the efficiency, scalability, and reproducibility of phenotyping studies. This advancement contributes to a deeper understanding of disease and the progression of precision medicine.

PMID:42538550 | DOI:10.1186/s13326-026-00364-7

BMC Palliat Care. 2026 Jul 31;25(1):223. doi: 10.1186/s12904-026-02266-y.

ABSTRACT

BACKGROUND: Strong opioids are central to effective symptom control in palliative care. In cases of complex symptom burden, primary care teams frequently rely on palliative care consultation services (PCCSs) for expert guidance. This survey explored the recommendations issued by hospital-based PCCS teams regarding the use of strong opioids in patients with advanced disease (e.g. clinical indications, opioid agent).

METHODS: A closed online survey was conducted via the SoSci Survey platform. All PCCS teams registered with the German Association for Palliative Medicine were invited to participate in November 2024, with a reminder sent three weeks later.

RESULTS: Thirty-nine PCCS teams participated (21 university hospitals, 18 general hospitals). All respondents agreed on the indication for strong opioids in cancer-related pain and dyspnea. Differences emerged regarding the use of opioids in patients with non-malignant conditions: although most PCCS considered opioids appropriate for dyspnea associated with pulmonary (n = 37) or cardiac disease (n = 33), non-cancer pain was less consistently endorsed (n = 20). Hydromorphone and morphine were the most commonly used opioids (> 30 services reporting frequent use), whereas the use of fentanyl, oxycodone, and buprenorphine varied widely across services.

CONCLUSIONS: There is consensus regarding the use of opioids in patients with cancer-related pain and dyspnea. The differing approaches to their use for symptoms caused by non-malignant conditions suggest varying clinical interpretations and underscore the need for further research and clearer guidelines.

PMID:42538548 | DOI:10.1186/s12904-026-02266-y

BMC Oral Health. 2026 Jul 30;26(1):1359. doi: 10.1186/s12903-026-09423-y.

ABSTRACT

AIM: The study aim was to evaluate the fracture resistance of premolar teeth with class V cavities restored with two types of polyethylene fibers using two different techniques of fiber placement in comparison to traditional composite restoration.

METHOD: Seventy-five intact maxillary premolar teeth were randomly divided into five groups (n = 15). Group 1 (control): class V cavities were filled with flowable resin composite, Beautifil flow plus F03; Group2 (Ribbond MD): Ribbond fiber placed horizontally in a mesiodistal orientation on the axial wall of the cavity; Group 3 (Ribbond OG): Ribbond fiber placed on the axial wall of the cavity in an occlusogingival orientation; Group 4 (InFibra MD): InFibra fiber placed horizontally in a mesiodistal orientation on the axial wall of the cavity; Group 5 (InFibra OG): InFibra fiber placed on the axial wall of the cavity in an occlusogingival orientation. After fiber placement, all cavities were filled with the same flowable resin composite, Beautifil flow plus F03 and cured for 10 s. Fracture resistance was assessed using a universal testing machine. Failure mode was also analyzed using magnification loupes.

RESULTS: A one-way ANOVA that was performed to assess fracture resistance across the five groups, showed no statistically meaningful differences among groups (F = 0.3034, p = 0.8722), with an extremely small effect size (η² = 0.0572). Post hoc analyses with Tukey’s HSD revealed that no pairwise differences were significant (p > 0.05). Failure mode results revealed 60% favorable fractures in the control group, Ribbond MD and Ribbond OG each demonstrated 20% favorable fractures, whereas InFibra MD and InFibra OG recorded no favorable fractures.

CONCLUSION: The incorporation of polyethylene fibers (Ribbond or InFibra) into moderately deep Class V cavities did not significantly enhance the fracture resistance of the teeth. Furthermore, the addition of these fibers was associated with a higher frequency of unfavorable fractures.

PMID:42538536 | DOI:10.1186/s12903-026-09423-y

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