Category: Statistics

Stat Med. 2026 Mar;45(6-7):e70465. doi: 10.1002/sim.70465.

ABSTRACT

Publication bias (PB) poses a significant threat to meta-analysis of diagnostic studies, as studies yielding significant results are more likely to be published in scientific journals, leading to the synthesized diagnostic capacity possibly being overestimated. Sensitivity analysis provides a flexible method to address PB by assuming different proportions of unpublished studies. Most existing methods addressing PB in meta-analysis of diagnostic studies are based on the bivariate normal model using normal approximations. However, they are unsuitable for meta-analysis with sparse data, which is common in diagnostic studies with high sensitivities or specificities. Alternatively, the bivariate binomial model relies on the exact within-study model and has better finite sample properties. To address PB in the bivariate binomial model, we model the selective publication process of diagnostic studies by extending the Copas t-statistic model and propose the likelihood conditional on published and estimation strategies. Our proposal provides an interpretable way to address PB on the summary receiver operating characteristic curve, an essential tool for synthesizing diagnostic accuracy. We show the practicability of the proposed method on several real-world meta-analyses of diagnostic studies and evaluate the performance by simulation studies.

PMID:41847888 | DOI:10.1002/sim.70465

Emerg Med Australas. 2026 Apr;38(2):e70245. doi: 10.1111/1742-6723.70245.

ABSTRACT

OBJECTIVE: The National Blood Authority (NBA) provides a Major Haemorrhage Protocol (MHP) template for Australian hospitals to develop and modify an MHP algorithm for their needs. However, it is unclear whether the evidence-based guidance from NBA is utilised by individual facilities. The aims of this study were to: (1) establish the baseline composition of MHP from public hospitals across Queensland and (2) compare content using the NBA algorithm and evidence-based recommendations.

METHODS: An explanatory qualitative design was used. Individual health service MHP were assessed against the NBA algorithm by a minimum of two members of the research team.

RESULTS: Seventy-eight MHP algorithms were retrieved from 113 hospitals and health facilities within Queensland. 99% (n = 77) of algorithms provided recommendations for red blood cell delivery and fibrinogen replacement. Variations existed on the availability of fresh blood products between hospitals and geographical locations. 90% of algorithms (n = 70) contained activation criteria; 21% (n = 14) incorporated additional non-NBA specific criteria. Less than half of MHP algorithms (n = 30, 40%) contained information regarding the management of critically bleeding paediatric patients.

CONCLUSION: There is significant variability in the content of MHP algorithms across Queensland, Australia, despite the availability of evidence-based guidelines for patients who are severely bleeding. Whilst individual health facilities are encouraged to modify MHPs to suit local contexts, the evidence on how to safely accomplish this remains limited and could account for the variations identified in this study. Further guidance is required for hospitals with restricted access to blood products, limited pathology testing capabilities, and who manage critically bleeding paediatric patients.

PMID:41847872 | DOI:10.1111/1742-6723.70245

Eur J Public Health. 2026 Mar 14;36(2):ckag029. doi: 10.1093/eurpub/ckag029.

ABSTRACT

With increasing life expectancy, multimorbidity represents a growing global challenge, affecting quality of life. We analyzed electronic health records of individuals aged 45-74 from Catalonia, Spain (2007-2021), who were healthy at the end of 2007. We use sequence and cluster analysis to describe and categorize monthly disease accumulation patterns, from healthy to one or multiple conditions or death, involving four disease groups with the highest global morbidity and mortality burdens. We further investigate the association between identified clusters and sociodemographic factors and the association of cluster membership with healthcare utilization. Approximately 36% of individuals remained healthy throughout the study, while the remainder transitioned to single or multiple morbidity and/or died. A higher number of conditions in a given month increased transition probability, with metabolic and hypertensive conditions being the most common entry points. We identified nine disease accumulation trajectories linked to sociodemographic characteristics: Women were more likely to be in clusters involving neurodegenerative conditions and men in those involving cardiovascular and cancer conditions. Higher-income individuals were more likely to be in lower morbidity clusters, except the cancer multimorbidity cluster. Healthcare utilization was elevated in all clusters relative to the healthy group, with notably higher emergency use in cardiovascular clusters and more hospital admissions in cancer-related clusters. The study shows that disease accumulation follows identifiable patterns linked to sociodemographic factors and underscores the propagative nature of multimorbidity. Further, healthcare utilization is shaped more by condition type than by the number, highlighting the need for targeted health services.

PMID:41847870 | DOI:10.1093/eurpub/ckag029

Eur J Public Health. 2026 Mar 14;36(2):ckag028. doi: 10.1093/eurpub/ckag028.

ABSTRACT

Vaccination is a modifiable behaviour resulting from a complex decision-making process influenced by a wide range of factors, including the ‘7Cs’ model (confidence, complacency, constraints, calculation, collective responsibility, compliance, and conspiracy) and the ability to find, understand, evaluate and use vaccine information. This work aimed to analyse the intention to receive a booster dose of the COVID-19 vaccine in Spain in the subsequent rollout of the COVID-19 vaccination campaign and how it was influenced by COVID-19 vaccination health literacy and the ‘7Cs’ determinants of vaccine hesitancy. A descriptive cross-sectional study was conducted in February 2022 using an online survey. The sample comprised 1067 participants aged 18 or older, representative of the Spanish general population. Willingness to receive an additional booster dose of the COVID-19 vaccine was assessed using a single yes/no answer question. Determinants of vaccine readiness were evaluated through seven statements aligned with the 7Cs model, adapted to the COVID-19 context. A multivariable logistic regression showed that vaccination intention was influenced by Confidence (OR = 3.79; 95% CI = 2.58-5.58), Calculation (OR = 0.63; 95% CI = 0.45-0.90), Collective Responsibility (OR = 0.52; 95% CI = 0.32-0.86), Compliance (OR = 2.10; 95% CI = 1.42-3.09), Conspiracy (OR = 0.46; 95% CI = 0.29-0.74), and vaccine related HL (OR = 1.03; 95% CI = 1.02-1.06). Fostering vaccination health literacy, strengthening trust in science and health professionals, fighting misinformation and enhancing collective responsibility are relevant aspects for designing effective vaccination campaigns.

PMID:41847868 | DOI:10.1093/eurpub/ckag028

Toxicol Mech Methods. 2026 Mar 18:1-16. doi: 10.1080/15376516.2026.2645333. Online ahead of print.

ABSTRACT

Arsenic (As) and cadmium (Cd) frequently co-occur in groundwater and target renal proximal tubules. Although each metal can engage ferroptosis pathways, how co-exposure shapes the integrated transcript-protein-lipid ROS axis remains unclear. Human HK-2 cells were exposed for 24 h to commonly used experimental concentrations of As (10 µM), Cd (10 µM), or As + Cd (5 µM + 5 µM). We profiled (i) a focused ferroptosis/oxidative stress gene panel and visualized Z-score heatmaps; (ii) ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, PTGS2, TFR1, ferritin heavy/light chains (FTH/FTL), LC3, Bax/Bcl-2, cleaved caspase-3) by Western blot with densitometric analysis; and (iii) lipid peroxidation using BODIPY 581/591 C11 imaging (oxidized green/reduced red). Statistical analyses were performed using one-way ANOVA followed by Tukey’s post hoc test. These readouts were interpreted alongside measurements of cell viability, ROS, MDA, and metabolomics profiling. Co-exposure produced the most coherent transcriptional shifts across modules regulating iron handling, glutathione-cysteine metabolism, lipid remodeling, CoQ/mitochondrial function, macroautophagy, and NRF2 signaling. Protein analyses corroborated pathway activation: GPX4 and SLC7A11 decreased, whereas ACSL4, PTGS2, and TFR1 increased. FTH/FTL exhibited a downward trend, and LC3-II levels increased, consistent with impaired peroxide detoxification, enhanced polyunsaturated fatty acid (PUFA)-phospholipid acylation, increased iron import, and autophagy engagement. BODIPY C11 imaging revealed the highest oxidized fraction in the As + Cd group, indicating a maximal lipid-peroxide burden. As and Cd act cooperatively to (1) weaken the GPX4-xCT (cystine/glutamate antiporter; SLC7A11) antioxidant axis, (2) increase iron availability and iron-handling stress, and (3) remodel membrane PUFA pools, collectively tipping renal epithelial cells toward ferroptosis. These multi-layer signatures nominate ferroptosis inhibition and iron handling as potential therapeutic targets for mixed-metal nephrotoxicity.

PMID:41847867 | DOI:10.1080/15376516.2026.2645333

Acta Odontol Scand. 2026 Mar 18;85:116-124. doi: 10.2340/aos.v85.45574.

ABSTRACT

OBJECTIVE: This study aimed to investigate the following: (1) the preferences of public dentists for procedures and materials in carious or non-carious pulp exposure of permanent teeth; (2) how factors such as clinical experience, scientific literature reading, and material availability affect their choices; (3) the self-assessed risk of root canal treatment after pulp capping.

MATERIALS AND METHODS: An online questionnaire consisting of 20 multiple choice and open-ended questions was e-mailed to Norwegian public dental clinics. It assessed dentists’ material preferences for direct pulp capping for carious or non-carious exposures, alongside factors such as years since graduation, scientific literature engagement, availability of materials, and clinical scenario choices. Respondents were also asked to estimate and reason long-term outcomes of their chosen materials. Standardized case descriptions ensured shared clinical understanding. Data were statistically analyzed and p-values ≤ 0.05 were considered statistically significant.

RESULTS: A total of 218 (23.9%) dentists responded. Direct pulp capping was preferred by 65% of respondents, with chemically curing materials – primarily calcium hydroxide – being most used. Chi-square analyses showed that dentists with fewer years of experience and those who had read scientific literature were more likely to prefer calcium silicate materials; however, these variables were not statistically significant predictors in the logistic regression models. Material availability was the strongest predictor of preference, with significantly increased odds of selecting calcium silicates or light-curing materials when available. ‘Satisfied with clinical results for the chosen material’ was the most frequently reported reason for material selection.

CONCLUSION: Most respondents in this study preferred calcium hydroxide for direct pulp capping in permanent teeth with closed apices, despite the superior clinical outcomes of hydraulic calcium silicates. Material availability in the clinic was the primary factor influencing dentists’ choices, surpassing clinical experience and scientific literature engagement.

PMID:41847838 | DOI:10.2340/aos.v85.45574

Stat Methods Med Res. 2026 Mar 18:9622802261418211. doi: 10.1177/09622802261418211. Online ahead of print.

ABSTRACT

In interventional health studies, causal mediation analysis can be employed to investigate mechanisms through which the intervention affects the targeted health outcome. Identifying direct and indirect effects from empirical data become complicated, however, when a confounder of the mediator-outcome association is itself affected by the treatment. Here, we investigate identification of mediational effects under such post-treatment confounding in a setting with a longitudinal mediator, time-to-event outcome and an ordinal treatment-dependent confounder. If the treatment affects the treatment-dependent confounder only in one direction (monotonicity), we show that the mediational effects are identified up to stratum-specific sensitivity parameters and derive their empirical non-parametric expressions. The feasibility of the monotonicity assumption can be assessed using empirical data, based on restrictions on the marginal distributions of counterfactuals of the treatment-dependent confounder. In an empirical analysis, we use data from the Finnish Diabetes Prevention Study to assess the extent to which the effect of a lifestyle intervention on avoiding type 2 diabetes is mediated through weight reduction in a high-risk population, with other health-related changes acting as treatment-dependent confounders. We avoid pitfalls related to post-treatment conditioning by treating the mediator as a functional entity and defining the time-to-event outcome as a restricted disease-free time.

PMID:41847826 | DOI:10.1177/09622802261418211

Vestn Oftalmol. 2026;142(1):108-111. doi: 10.17116/oftalma2026142011108.

ABSTRACT

Glaucoma remains one of the leading causes of irreversible vision loss, making it one of the most pressing problems in modern public health.

PURPOSE: This study aimed to identify trends in glaucoma morbidity among adults, adolescents, and children in the Republic of Uzbekistan based on a comprehensive analysis of its prevalence.

MATERIAL AND METHODS: The study used statistical data from the Republican Medical Information Center of the Ministry of Health of the Republic of Uzbekistan for the period 2016-2022. Changes in glaucoma morbidity in 2017-2022 years were analyzed using statistical methods to identify trends and patterns.

RESULTS: The analysis of changes in glaucoma prevalence demonstrated increases in 2016, 2018, and 2021, indicating the potential influence of factors affecting the conditions of glaucoma diagnosis and treatment.

CONCLUSION: The findings confirm the growing relevance of glaucoma as a serious medical and social problem, particularly among the adult population. The results may serve as a basis for developing effective preventive measures and optimizing treatment strategies to reduce the rate of irreversible vision loss.

PMID:41847815 | DOI:10.17116/oftalma2026142011108

Vestn Oftalmol. 2026;142(1):79-86. doi: 10.17116/oftalma202614201179.

ABSTRACT

PURPOSE: The secondary objectives of the study were to describe the sociodemographic and clinical characteristics of patients with inherited retinal dystrophy (IRD) phenotypes, including Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP), to characterize the diagnostic and treatment pathways of patients with confirmed biallelic mutations in the RPE65 and/or RLBP1 genes, and to estimate the prevalence of RPE65-associated inherited retinopathy and RLBP1-associated pathology in Russia.

MATERIAL AND METHODS: This noninterventional cohort study was conducted using retrospective data collected from patients with LCA and RP phenotypes in Russia and annual prospective follow-up of patients with IRDs caused by biallelic mutations in the RPE65 or RLBP1 genes. The registry was formed between July 20, 2022 and March 3, 2025. Eligible participants were entered into the database, followed by a two-stage genetic diagnostic algorithm to confirm biallelic mutations in the RPE65 or RLBP1 genes. The data were entered into standardized electronic case report forms, verified, and analyzed using descriptive statistical methods.

RESULTS: The study included 2425 patients from 83 regions of the Russian Federation diagnosed with IRDs. The majority of patients were from Moscow, the Moscow Region, the Republic of Dagestan, the Republic of Tatarstan, Saint Petersburg, and the Republic of Bashkortostan. The mean age was 23.22±16.74 years, pediatric patients accounted for 51.34% of analyzed cases. Females and males comprised 47.01% and 52.99% of the cohort, respectively. In patients with confirmed biallelic mutations in the RPE65 gene, disease onset was characterized by nyctalopia (47.5%), nystagmus (40%), pigment redistribution (40%), non-recordable/extinguished electroretinogram (45.0%), and prolonged dark adaptation (35.0%). Mean best-corrected visual acuity was reduced (OD: 0.14±0.12; OS: 0.15±0.13), while central retinal thickness in the foveal region remained relatively preserved (OD: 178.70±38.43 µm; OS: 179.17±35.97 µm).

CONCLUSION: The study “Registry of patients with inherited retinal dystrophies caused by confirmed biallelic mutations in the RPE65 and RLBP1 genes in Russia (REGINA)” allowed evaluation of a representative IRD cohort, providing a detailed description of key clinical, social, and demographic characteristics.

PMID:41847811 | DOI:10.17116/oftalma202614201179

Vestn Oftalmol. 2026;142(1):70-78. doi: 10.17116/oftalma202614201170.

ABSTRACT

PURPOSE: The primary objective of the study was to investigate and describe the molecular genetic characteristics of patients with inherited retinal dystrophies (IRDs) presenting with phenotypes of Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP), taking into account clinical polymorphism.

MATERIAL AND METHODS: This noninterventional cohort study was conducted in Russia by collecting retrospective data from patients with LCA and RP phenotypes and annual prospective follow-up of patients with IRDs caused by biallelic mutations in the RPE65 or RLBP1 genes, entered into the registry between July 20, 2022 and March 3, 2025. Eligible participants were entered into the IRD database, followed by a two-stage genetic diagnostic algorithm to confirm the presence of biallelic mutations in RPE65 or RLBP1. The data were entered into standardized electronic case report forms, verified, and analyzed using descriptive statistical methods.

RESULTS: The study cohort included 2425 patients with IRDs from 83 regions of the Russian Federation. The mean age was 23.22±16.74 years, with predominance of pediatric patients (51.34%) and males (52.99%).

Genetic testing was performed in two stages. At the first stage, mutations in RPE65 and/or RLBP1 were identified in 84 (3.52%) of 2388 examined patients. The second stage involving direct Sanger sequencing was conducted in 48 (2.01%) patients, it confirmed biallelic mutations in RPE65 in 1.68% and in RLBP1 in 0.04% of cases. In one case, mutations in both genes were verified. Among RPE65 variants, 61 mutations were identified, including frequent pathogenic variants (c.304G>T, c.272G>A, c.370C>T); seven variants were detected in the RLBP1 gene.

The frequency of biallelic RPE65 mutations in the subgroup with LCA/RP phenotype was 1.68%, and 1.65% in the overall IRD cohort, which is consistent with published data from European populations.

CONCLUSION: The study “Registry of patients with inherited retinal dystrophies caused by confirmed biallelic mutations in the RPE65 and RLBP1 genes in Russia” allowed characterization of the key molecular genetic features of a representative sample of patients with IRDs.

PMID:41847810 | DOI:10.17116/oftalma202614201170