Category: Statistics

Eur J Health Econ. 2025 Nov 20. doi: 10.1007/s10198-025-01871-7. Online ahead of print.

ABSTRACT

Alternative payment models (APMs) aim to improve efficiency and fairness in healthcare by shifting financial responsibility from payers to providers. Given their prospective nature, APMs require effective risk adjustment (RA) to prevent risk-selection incentives. RA design comes with complex trade-offs between risk selection, cost control and gaming. In the light of these trade-offs, thorough ex-ante evaluation of RA models is crucial. Traditionally, RA-model evaluation in the context of APMs has heavily relied on statistical metrics like R-squared. While useful for assessing model fit, these metrics often fail to capture the full spectrum of relevant incentives. This study therefore addresses the question: “What do meaningful incentive metrics for ex-ante evaluation of RA models look like in the context of prospective APMs for healthcare providers?” We conducted a literature review and consulted experts to synthesize existing work on RA evaluation. This informed the development of a conceptual framework for defining incentive metrics, distinguishing among risk-selection, cost-control, and gaming incentives. We applied our framework in a simulation of prospective payments to primary care practices (PCPs) in the Netherlands, using 2019 claims data from 346 PCPs (N = 1.4 M patients). The analysis focused on selection incentives, comparing traditional statistical metrics with metrics derived from our framework. Results show that statistical metrics like R-squared fall short in assessing selection incentives compared to our incentive metrics. This highlights the need for tailored incentive metrics for the ex-ante evaluation of RA models that are grounded in a thorough understanding of relevant provider behaviors in the light of APM goals.

PMID:41264066 | DOI:10.1007/s10198-025-01871-7

Mol Biol Rep. 2025 Nov 20;53(1):104. doi: 10.1007/s11033-025-11278-5.

ABSTRACT

BACKGROUND: Toll-like receptor 3 (TLR 3) abnormal inflammatory response was described as one of the possible mechanisms implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). However, the genetic predisposition of TLR 3 to these disorders’ onset is still unclear. Therefore, the predisposition of TLR 3 functional variants L412F (rs3775291) and F459L (rs3775290) was examined in both disorders.

METHODS AND RESULTS: In a case-control study, 260 controls, 260 SCZ, and 130 BD patients were recruited and genotyped by PCR-RFLP. Genotypes, alleles, and haplotypes frequencies were compared between controls and patients based on clinical features. Statistical analyses were adjusted by gender and age and validated by Bonferroni correction. In the dominant model, our results showed significantly higher L412F AA + GA frequency in controls compared to BD patients (p_adjusted=0.004; OR_adjusted=0.5) and type I BD patients (p_adjusted=0.009; OR_adjusted=0.5). Moreover, BD BPRS scores were significantly lower in L412F AA + GA carriers compared to GG carriers (p = 0.001) before treatment. Otherwise, F459L TT + CT and minor allele frequencies were significantly elevated in the paranoid subgroup compared to controls (p = 0.004; OR = 2.1, p = 0.002; OR = 1.8, respectively). After antipsychotic treatment, SCZ SANS scores decreased significantly in F459L TT + CT and CC carriers (p < 10^{– 4}) and in TT + CT carriers compared to CC carriers (p = 0.001).

CONCLUSIONS: The present study suggests that L412F could be a protective genetic factor from BD onset. However, F459L could be a genetic risk factor for the paranoid subtype and a potential genetic predictor of SCZ negative symptoms treatment improvement.

PMID:41264056 | DOI:10.1007/s11033-025-11278-5

Discov Ment Health. 2025 Nov 20;5(1):181. doi: 10.1007/s44192-025-00328-w.

ABSTRACT

AIM(S): This study aimed to explore the prevalence of mental health symptoms in current and former elite kickboxers and to establish whether these mental health symptoms were associated with severe musculoskeletal injuries and/or concussions.

METHODS: A cross-sectional study was conducted by utilizing an electronic questionnaire among current and former elite kickboxers from the highest and second highest international level. Validated screening questionnaires from the International Olympic Committee Sport Mental Health Assessment Tool 1 (SMHAT-1) were used to asses mental health symptoms.

RESULTS: The most prevalent mental health symptoms among current elite kickboxers (N = 45) were psychological distress (57%) and disordered eating (63%). Among former elite kickboxers (N = 29), the most prevalent mental health symptoms were 36% for psychological distress and 43% for alcohol misuse. Additionally, no statistically significant associations were found between mental health symptoms and severe musculoskeletal injuries and/or concussions among current and former elite kickboxers.

CONCLUSIONS: The substantial prevalence rates of mental health symptoms among current and former elite kickboxers emphasize the need for increased attention in this area. No associations were found between the potential contributing factors and mental health symptoms among current and former elite kickboxers. While further research is needed, raising awareness as well as developing preventive and supportive measures to assist elite kickboxers with personal and career development should be prioritized, both inside and outside the ring.

PMID:41264054 | DOI:10.1007/s44192-025-00328-w

Discov Oncol. 2025 Nov 20. doi: 10.1007/s12672-025-03971-5. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common type of malignant tumor of the pancreas with high aggressiveness and low prognosis. Due to the insidious early symptoms of pancreatic adenocarcinoma, patients are mostly diagnosed at advanced stages with a high incidence of nerve invasion. With the rapid development of precision medicine, studying the molecular mechanisms behind PDAC can help its diagnosis and treatment, which is conducive to improving the prognosis of PDAC patients.

OBJECTIVE: To explore the correlation between LAMA3 expression and nerve invasion in pancreatic ductal adenocarcinoma tissues.

METHODS: Ninety-four patients with pathologically confirmed diagnosis of PDAC in the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Anhui Medical University were retrospectively collected from January 2023 to December 2023, and the patients’ clinicopathological data were collected and followed up for 5 months. Immunohistochemical staining was applied to detect the expression level of LAMA3 in cancer tissues, and paraneoplastic tissues were used as controls to compare the differences in the expression level of LAMA3. The Kaplan-Meier method was used to draw the survival curves, and the Cox proportional risk regression model was set up to analyze the correlation between the expression of LAMA3 and the nerve invasion.

RESULTS: Immunohistochemical staining results showed that LAMA3 was mainly expressed in the cytoplasm and appeared as yellow to brown granules.The positive expression rate of LAMA3 in PDAC cancer tissues was 63.83% (60/94), which was significantly higher than that in paracancerous tissues (12.77%, 12/84), and the difference between the two groups was statistically significant (x² = 51.862, P < 0.001). Patients were categorized into nerve invasion negative (n = 30) and nerve invasion positive (n = 64) according to the presence or absence of nerve invasion.Cox proportional analysis regression results showed that the LAMA3 expression level was an independent risk factor affecting the occurrence of nerve invasion in PDAC patients. Survival analysis showed that median OS was significantly lower in patients with high LAMA3 expression and development of vascular invasion than in patients with low LAMA3 expression and no vascular invasion (P < 0.001); in TNM staging, median OS was significantly lower in patients with stage II than in patients with stage I (P < 0.001).

CONCLUSION: LAMA3 expression level is an independent risk factor for the occurrence of neuroinvasion in PDAC patients; LAMA3 expression level, TNM staging and prognosis of PDAC patients are correlated; LAMA3 expression level may serve as a valuable biomarker for the occurrence, development, and prediction of prognosis of patients with PDAC, and also as a potential therapeutic target for PDAC patients.

PMID:41264049 | DOI:10.1007/s12672-025-03971-5

Discov Oncol. 2025 Nov 20. doi: 10.1007/s12672-025-04113-7. Online ahead of print.

ABSTRACT

BACKGROUND: Glioma is the most common primary brain tumor in adults, with glioblastoma (GBM) being the most aggressive subtype. The causal relationship between platelet count and glioma risk remains unclear. This study aimed to evaluate this relationship using Mendelian randomization (MR) methodology.

METHODS: We performed MR analysis using 707 platelet count-associated SNPs as instrumental variables, validated by three statistical methods (IVW radial, Maximum likelihood, and MR IVW). Genome-wide association study (GWAS) identified glioma susceptibility loci. We also measured mRNA expression of 4 platelet-related genes (THPO, GP6, ITGA2B, MPL) in glioma cell lines (U87-MG and U251-MG) and normal astrocytes (NHA) using qRT-PCR.

RESULTS: MR analysis demonstrated that genetically determined increased platelet count significantly reduces glioma risk (OR: 0.721-0.724, 95% CI: 0.554-0.938, P < 0.05), representing approximately 27-28% risk reduction per standard deviation increase. GWAS identified multiple susceptibility loci across chromosomes 1, 5, 7, 8, 9, 11, 16, and 20. This protective association was confirmed in GBM subtype analysis (OR: 0.65-0.95). All 4 platelet-related genes showed significant downregulation in glioma cells compared to normal astrocytes (P < 0.001), with expression ranging from 0.31 to 0.48-fold of controls.

CONCLUSIONS: This study establishes a causal relationship between platelet count and glioma risk through genetic evidence. Increased platelet count confers protection against glioma, including GBM. Suppressed expression of platelet-related genes in glioma cells supports this finding. These results provide new insights into glioma pathogenesis and suggest potential for platelet-based prevention strategies and biomarker development.

PMID:41264048 | DOI:10.1007/s12672-025-04113-7

Mol Biol Rep. 2025 Nov 20;53(1):105. doi: 10.1007/s11033-025-11272-x.

ABSTRACT

BACKGROUND: Occupational asthma (OA), particularly diisocyanate-induced asthma (DA), is a common work-related respiratory condition. Genetic variations in antioxidant enzyme genes, such as glutathione S-transferases (GSTs), may influence susceptibility to OA. This study investigates associations between polymorphisms in GSTM1, GSTT1, and GSTP1 (rs1695, rs1138272) and DA risk in an Iraqi Arab male population.

METHODS: A total of 235 male workers exposed to diisocyanates were enrolled: 125 with DA and 110 exposed but asymptomatic controls. Genotyping was performed using multiplex-PCR and RFLP-PCR. Associations were analyzed under various genetic models, including combined genotypes.

RESULTS: No statistically significant associations were found between individual GSTP1 SNPs and overall DA risk. Combined analysis of variant alleles at both GSTP1 SNPs (rs1695 and rs1138272) suggested a nominal association with increased DA risk (OR = 2.05; 95% CI: 1.02-4.12; p = 0.04; adj. p = 0.24). Carriers of the GSTP1 rs1695 variant combined with the GSTT1-null genotype also showed a nominally increased risk (OR = 2.88; p = 0.04; adj. p = 0.12). Stratification by disease severity indicated that GSTM1-null and GSTT1-null genotypes were approximately twofold more frequent among patients with severe DA compared to controls (OR = 2.20; 95% CI:1.01-4.82; p = 0.04 and OR = 2.22; 95% CI: 1.06-4.67; p = 0.03, respectively).

CONCLUSION: While individual GST polymorphisms were not significantly associated with DA, certain combined genotypes, particularly those involving GSTP1 and GSTT1, showed nominal associations, and GSTM1-null and GSTT1-null genotypes may contribute to severe DA. This is the first study to assess these associations in an Arab population, providing valuable preliminary data for future occupational asthma research.

PMID:41264046 | DOI:10.1007/s11033-025-11272-x

Acta Parasitol. 2025 Nov 20;70(6):234. doi: 10.1007/s11686-025-01178-w.

ABSTRACT

PURPOSE: Cutaneous leishmaniasis (CL) is an endemic disease in Algeria. In southeastern regions, data concerning this infection are limited. Therefore, we aimed to assess the epidemiological status and identify the causative Leishmania spp. in El Meghaier province.

METHODS: A retrospective study was conducted between 2023 and 2024. Diagnosis was confirmed by microscopic examination. For patients with positive results, clinical and demographic data were recorded. Molecular analysis was then carried out on DNA extracted from Giemsa-stained slides to identify the Leishmania species.

RESULTS: In total 722 suspected cases were analyzed and only 118 were positive cases. A predominance in males was detected, and the most affected group age was [≥ 20] years old (N = 51; 43.2%). The statistical analysis showed strong association between age group and the positivity rate (X² = 37.59, P < 0.0001). Multiple lesions were observed in 72 patients (61.1%), most frequently located on the feet (76 cases; 64.4%) and hands (15 cases; 12.7%). Among the 118 microscopically positive samples, 53 were included for molecular analysis. Of these, 29 yielded a positive PCR amplification. Initial parasite typing was performed using PCR-ITS1, which detected Leishmania DNA in 14 samples (26.4%), predominantly L. major (92.8%). Samples negative by PCR-ITS1 were subsequently analyzed using nested ITS1-PCR, which identified 15 additional positives (38.5%). Sequencing of the amplified products confirmed the presence of L. major (66.6%) and L. infantum (13.3%).

CONCLUSION: These findings confirm, for the first time, the occurrence of both L. major and L. infantum in the study area. Further studies are needed to investigate the potential vectors and reservoirs involved.

PMID:41264036 | DOI:10.1007/s11686-025-01178-w

Neurosurg Rev. 2025 Nov 20;49(1):16. doi: 10.1007/s10143-025-03944-w.

ABSTRACT

Introduction Skull base surgery presents significant challenges due to the complex anatomy and proximity of tumors to critical neurovascular structures. While advancements in surgical techniques have improved outcomes, the risk of postoperative adverse events (AEs) remains substantial. This study provides a prospective analysis of AEs and associated risk factors in skull base surgery, leveraging data from a high-volume tertiary neurosurgical center. The analysis focuses on tumor location, surgical craniotomies, and patient-specific factors to identify predictors of complications and guide risk mitigation strategies. Methods Between January 2022 and December 2023, 236 adult patients undergoing skull base surgery were prospectively enrolled. AEs-defined as any complication occurring within 30 days postoperatively-were systematically documented. Data collection included patient demographics, tumor characteristics, surgical craniotomies, intraoperative findings, and postoperative outcomes to identify risk factors for AEs. Statistical analyses were performed to assess associations between these variables and postoperative complications. Results The study cohort had a mean age of 56.8 ± 12.7 years, with tumor distribution supratentorial (55.1%) and infratentorial (44.9%). The most frequently utilized surgical craniotomies were retrosigmoid (40.3%), pterional (39.4%), and later lateral supraorbital (6.4%). Overall, 28.8% of patients experienced AEs, with 22.5% neurosurgical (e.g., new-onset cranial nerve deficits) and 8.5% non-neurosurgical (e.g., thromboembolic events, infections). Older age and higher ASA scores (p = 0.01) were significant predictors of non-neurosurgical AEs. Revision surgery was required in 6.8% of cases. Infratentorial tumor location and prolonged operative times were strongly associated with an increased risk of surgical complications (p = 0.001), while the retrosigmoid craniotomy was a key risk factor for both neurosurgical AEs and revision surgeries (p = 0.001). ROC analysis showed that combining age and ASA score improved prediction of non-neurosurgical AEs (combined AUC = 0.78 vs. age AUC = 0.70; ASA AUC = 0.72). Conclusion Our findings highlight critical and actionable risk factors influencing neurosurgical outcomes. We demonstrate that infratentorial tumor location and prolonged surgical duration significantly increase the likelihood of surgery-related adverse events, with the retrosigmoid craniotomy particularly elevating these risks. Notably, advanced age and higher ASA scores robustly predict non-surgery-related complications, with a combined predictive accuracy superior to each factor individually. These insights underscore the importance of meticulous preoperative risk assessment and tailored surgical strategies, enabling clinicians to proactively manage high-risk patients and improve postoperative outcomes.

PMID:41264035 | DOI:10.1007/s10143-025-03944-w

World J Urol. 2025 Nov 20;43(1):708. doi: 10.1007/s00345-025-06005-5.

ABSTRACT

PURPOSE: Exposure to antibiotics in early life exerts profound impacts on the gut microbiota and is linked to various diseases. This study investigated the association between long-term or recurrent antibiotics use during early life(LRAU), genetic risk and urolithiasis incidence using a large-scale cohort.

METHODS: Participants in the UK Biobank who completed digestive health questionnaire were included in this cohort study. Multivariable Cox proportional hazards regression models were used to estimate the risk of incident urolithiasis for LRAU and polygenic risk score (PRS). Additionally, the potential interaction effects were assessed.

RESULTS: Over a median follow-up of 51 years, 3011 of the 121,746 participants developed urolithiasis. Compared to non-LRAU participants, those with LRAU exhibited higher risks of urolithiasis with HRs of 1.20 (95% CI 1.09-1.31). This association is still significant at 5-year intervals from ages 35 to 60. Participants with high and moderate PRS demonstrated increased risks of urolithiasis compared with low group, with HRs of 1.78 (95% CI 1.62-1.94) and 1.36 (1.23-1.49). When stratified by PRS, the significance of LRAU was no longer evident, but still could bring additional risk. Results in the sensitivity analyses were highly consistent with the primary analyses.

CONCLUSION: Both LRAU and a higher PRS are associated with an increased risk of urolithiasis. This association is significant for LRAU at 5-year intervals from ages 35 to 60. A dose-response correlation between PRS and urolithiasis incidence was indicated. LRAU could bring additional urolithiasis risk in participants with higher genetic risk.

PMID:41264027 | DOI:10.1007/s00345-025-06005-5

World J Urol. 2025 Nov 20;43(1):707. doi: 10.1007/s00345-025-06081-7.

ABSTRACT

PURPOSE: Nephrometry scores are essential tools for classifying and comparing tumor complexity and guiding surgical planning in partial nephrectomy. However, their performance in single-port robot-assisted partial nephrectomy (SP-RAPN) has not been formally assessed. We aimed to externally validate and compare the predictive performance of the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA), Radius-Exophytic/Endophytic-Nearness-Anterior/Posterior-Location (RENAL), and Simplified PADUA Renal (SPARE) nephrometry scores in patients undergoing SP-RAPN.

METHODS: We retrospectively reviewed 211 consecutive patients who underwent SP-RAPN for solitary ≤ cT2 renal tumors at two academic centers between 2019 and 2024. The primary endpoint was Trifecta achievement, defined as the simultaneous presence of negative surgical margins, absence of perioperative complications, and warm ischemia time ≤ 25 min. Discrimination and clinical utility of each nephrometry score were assessed using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). Multivariable logistic regression adjusted for relevant clinical covariates.

RESULTS: Trifecta was achieved in 50.7% of patients. The SPARE score demonstrated the highest discriminative performance (AUC 0.681), followed by PADUA (0.661) and RENAL (0.654), though these differences were not statistically significant. DCA showed overlapping net benefit curves, with SPARE offering marginally superior. Limitations include the retrospective design and underrepresentation of highly complex tumors.

CONCLUSIONS: PADUA, RENAL, and SPARE scores show comparable performance in predicting Trifecta achievement in the setting of SP-RAPN. SPARE may perform slightly better, and it represents a more practical choice for routine preoperative assessment due to its ease of use.

PMID:41264016 | DOI:10.1007/s00345-025-06081-7