Category: Statistics

Ther Innov Regul Sci. 2025 Aug 16. doi: 10.1007/s43441-025-00861-4. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular and oncology trials increasingly require large sample sizes and long follow-up periods. Several approaches have been developed to optimize sample size including sample size re-estimation based on the promising zone approach. With time-to-event endpoints, methods traditionally used to test for treatment effects are based on proportional hazards assumptions, which may not always hold. We propose an adaptive design wherein using interim data, Bayesian computation of Predictive Power (PP) guides the increase in sample size and/or the minimum follow-up duration.

METHODS: PROTECT IV is designed to evaluate mechanical circulatory support device vs. standard of care during high-risk percutaneous coronary intervention with the initial enrolment of 1252 patients and initial minimum follow-up of 12 months. The primary endpoint is the composite rate of all-cause death, stroke, durable left ventricular assist device implant or heart transplant, myocardial infarction or hospitalization for cardiovascular causes. The study will employ an adaptive increase in sample size and/or minimum follow-up at the Interim analysis. The adaptations utilize simulations to choose a new sample size up to 2500 and new minimal follow-up time up to 36 months that provides PP of at least 90%.

RESULTS: Via extensive simulations, we have examined the utility of the proposed design for situations like delayed treatment effect, early benefit only and in general crossing of survival curves. Separate Piece-wise Constant Hazard Models with non-influential (weakly-informative) Gamma-priors are fitted to the interim data for the two treatment arms, free from the proportional hazards assumptions, thus yielding more robust interim decision making. The Bayesian modeling facilitates sampling of future observations from the posterior predictive distributions with the predictive probability of trial success is computed via Monte-Carlo simulations. Simulation results show that the fitting Bayesian Piecewise Exponential models to the interim data along with the use of the posterior predictive distributions lead to more “specific” adaptation rules compared to the frequentist Conditional Power while the overall operating characteristics, type-I error and power, are similar.

CONCLUSION: For clinical trials with time-to-event endpoints and where crossing of survival curves might be anticipated at the planning stage, flexible modeling along with wholesome use of patient-level data such as the calculation of predictive power as proposed here, may be more robust and efficient in making interim decisions such as sample size increase than the traditional use of the conditional power based on summary statistics and proportional hazards assumption.

PMID:40819155 | DOI:10.1007/s43441-025-00861-4

Sci Rep. 2025 Aug 16;15(1):29995. doi: 10.1038/s41598-025-15761-8.

ABSTRACT

Acute block of hERG channels is the most common mechanism underlying drug-induced QT_C prolongation and potentially fatal Torsade de Pointes arrhythmia. Updates to ICH E14 Q&As now allow for using negative nonclinical data, including hERG, to support QT_C risk assessment in late-stage clinical development. To interpret the hERG results, understanding hERG assay reproducibility or hERG data variability is pivotal. Protocol and best practice recommendations have been provided with the goal of minimizing lab-to-lab data differences, but the impact remains unclear. To fill this knowledge gap, hERG data from a HESI-coordinated multi-laboratory study were leveraged. Using standardized protocol and following best practices for patch clamp studies, five laboratories tested 28 drugs using the manual patch clamp technique. Systematic differences in block potencies were observed for data generated by one laboratory for the first 21 drugs, and these differences disappeared for the last seven drugs. Exposure, pharmacological sensitivity of the cell lines, and cell/data qualities were ruled out as the factors underlying systematic differences. All laboratories retested two drugs and obtained results within 1.6X of the initial testings, except for another laboratory that obtained data for one drug that differed from its initial testing by 7.6X. Descriptive statistics and meta-analysis were applied to the dataset to estimate what the distribution in hERG block potencies would be if a laboratory were to test the same drug repeatedly. This measure, or hERG data variability, was ~ 5X. Based on these results, hERG block potency values within 5X of each other should not be considered different, since these values are within the natural data distribution of the hERG assay; laboratory-specific safety margin threshold may be required to account for systematic data differences.

PMID:40819150 | DOI:10.1038/s41598-025-15761-8

Ann Surg Oncol. 2025 Aug 16. doi: 10.1245/s10434-025-18037-7. Online ahead of print.

ABSTRACT

BACKGROUND: Stricture is a major adverse event following esophageal endoscopic submucosal dissection (ESD). Although postoperative esophageal stenosis after ESD is clearly associated with large mucosal defects, there are no quantitative criteria for the degree of the defect. We aimed to examine the predictive factors associated with the development of esophageal stenosis after ESD, and to explore quantitative indicators for predicting postoperative stenosis.

PATIENTS AND METHODS: A retrospective analysis of endoscopic data from patients with esophageal ESD was conducted. The area and perimeter of the resected mucosa defect were measured by Image Pro Plus 6.0. Logistic regression, receiver operating characteristic (ROC) curve, and nomogram model were adopted for analysis.

RESULTS: The median area of resected mucosal defect was 527.74 mm² (IQR 322.80-823.48), the median perimeter was 91.75 mm (IQR 71.69-118.32), and the median circumferential ratio was 33% (IQR 20-40). Owing to collinearity between the perimeter and area of the resected mucosal defect, these variables were analyzed individually in the multivariate analysis (r = 0.958, P < 0.001). All three factors mentioned above were identified as independent risk factors for postoperative esophageal stenosis (P < 0.05), while intraoperative muscularis propria injury was not (P > 0.05). On the basis of the above results, prediction models were constructed and validated internally. The concordance statistics (C-statistics) of the training and validation sets including perimeter or area were 0.875 and 0.830 and 0.747 and 0.835, respectively. The Hosmer-Lemeshow goodness-of-fit test results were not significant (P > 0.05).

CONCLUSIONS: Accurate quantification of the area and perimeter of resected mucosa by image analysis technology can accurately predict esophageal stenosis after ESD.

PMID:40819145 | DOI:10.1245/s10434-025-18037-7

Sci Rep. 2025 Aug 16;15(1):30030. doi: 10.1038/s41598-025-14973-2.

ABSTRACT

There is a knowledge gap about the quantitative aspects of mycorrhizal fungi’s influence on ecological succession on tailings. Here, we demonstrate that inoculating mine tailings with 2% fungi yields significantly better results in terms of plant biomass and lower lipid peroxidation compared to 1% and 0%, both when growing Agrostis capillaris alone and in combination with Melilotus albus. Lipid peroxidation in the A. capillaris is positively predicted by Cu, and negatively predicted by the total Kjeldahl nitrogen in plants. The biomass of M. albus is positively predicted by the N/P ratio, and negatively by Cu concentration in the plant. This improvement was related to differences between the Technosols properties at the end of the experiment (pH, EC, N-NH₄⁺, N-NO₃^–), which modulated the changes of the tailing material properties from the wet to the dry state, and to differences in the accumulation factors of Cu and Pb from substrate to plant roots, and of the transfer factors from roots to aboveground parts. This is the first time that the effects of such a slight increase in fungal inoculum percentage have been reported. Fine-tuning the fungi treatment can lead to cost-effective techniques for tailings remediation. Block diagrams of an eco-technology are proposed.

PMID:40819128 | DOI:10.1038/s41598-025-14973-2

Sci Rep. 2025 Aug 16;15(1):29991. doi: 10.1038/s41598-025-15815-x.

ABSTRACT

Mineral elements in colostrum play crucial roles in neonatal growth and development. This study assessed the concentrations of ten essential mineral elements in the colostrum of moderately preterm and full-term mothers in Ghana, and examined their associations with maternal characteristics. A total of 47 mothers provided single 12 mL colostrum samples collected between postpartum days 1 to 4 using standardized, aseptic manual expression procedures. The samples were digested and analyzed using ICP-OES. Statistical analyses included tests for normality, Spearman correlation, and group comparisons using Kruskal-Wallis and Mann-Whitney U tests. The concentrations ranged from 0.1 ± 0.0 mg/L (Se) to 602.6 ± 77.6 mg/L (K). Significant positive correlations were observed among several mineral pairs. Notably, potassium levels were significantly associated with maternal employment status (p = 0.047), and zinc levels were significantly related to maternal parity (p = 0.028). Although differences between preterm and full-term samples were not statistically significant, preterm colostrum showed trends of higher zinc and potassium concentrations. Compared to global data, the Ghanaian samples exhibited relatively elevated levels of phosphorus, sodium, and selenium. These findings provide foundational data on early breast milk composition in Ghana and highlight maternal and gestational factors that may influence neonatal mineral intake.

PMID:40819102 | DOI:10.1038/s41598-025-15815-x

BMC Musculoskelet Disord. 2025 Aug 16;26(1):793. doi: 10.1186/s12891-025-09028-6.

ABSTRACT

BACKGROUND: Frozen shoulder, also clinically known as adhesive capsulitis, is characterized by pain, stiffness, and gradual loss of passive or active glenohumeral range of motion. It leads to marked reduction in shoulder mobility, impacting daily activities and quality of life. This study aims to evaluate the effectiveness of the Spencer muscle energy technique (SMET) for frozen shoulder patients.

METHODS: For this systematic review and meta-analysis, we used PubMed, Cochrane Library, Embase, and Physiotherapy Evidence Database (PEDro) for searching from inception to January 20, 2025. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and independent authors selected clinical control trials that compare the effect of the Spencer muscle energy technique and comparative treatment in individuals with frozen shoulder. The outcomes were pain, function, and shoulder range of motion (ROM). Two authors independently did data extraction. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool, and the overall quality of the evidence was evaluated using the PEDro scale.

RESULTS: Nine studies were included in this review, and eight studies were included in the meta-analysis. Results indicated that SMET and other comparative treatments showed no statistical difference in the pain, flexion ROM, and abduction ROM standard mean difference (SMD). -0.19; 95% CI (-0.83, 0.45); I²=84%, (MD), 7.65; 95% CI (-11.7, 26.9); I²=95%, MD, 11.32; 95% CI (-9.10, 31.74); I²=96%, respectively. SMET was a statistically significant effect for shoulder function, SMD – 0.5; 95% CI (-0.78, -0.22); I² = 41%. SMET had an inferior effect on shoulder external rotation and extension ROM MD, 9.74; 95% CI (2.38, 17.10) I² = 92, MD, 2.55; 95% CI (1.14, 3.96); I² = 0 respectively.

CONCLUSION: This systematic review and meta-analysis indicates that SMET shows promise in improving shoulder function in patients with frozen shoulder; however, evidence is inconsistent for pain and ROM outcomes compared to other manual therapies. Further studies should explore the effect of SMET across different phases of frozen shoulder to determine the optimal timing for intervention through large, high-quality, and well-designed randomized control trials.

PROSPERO REGISTRATION NUMBER: CRD42024605780.

PMID:40819086 | DOI:10.1186/s12891-025-09028-6

BMC Musculoskelet Disord. 2025 Aug 16;26(1):795. doi: 10.1186/s12891-025-09050-8.

ABSTRACT

OBJECTIVE: Ankle fracture involving the posterior malleolus is characterized by poor prognosis, and its risk factors remain controversial. This study aims to evaluate the influence of posterior malleolar fractures with different step-off levels on posttraumatic osteoarthritis and functional prognosis and identify the related risk factors that affect the clinical prognosis of posterior malleolar fractures.

METHODS: The information of 134 patients with ankle fractures involving the posterior malleolus from January 2016 to December 2021 was retrospectively collected. The patients’ posterior malleolar fracture reduction quality, fracture healing status, and severity of ankle posttraumatic osteoarthritis (Kellgren-Lawrence scale) were evaluated by radiology, and the ankle function was assessed using Olerud-Molander score, visual analogue scale (VAS) score, and range of ankle motion.

RESULTS: All 134 patients achieved fracture healing, with an average follow-up period of 42 (13,78) months. Thirty-nine patients (29%) showed positive ankle posttraumatic osteoarthritis. The average Olerud-Molander score was 89.9 (70,100), the average VAS score was 1.0 (0,5), and the ankle dorsiflexion restriction was 4.0° (0°,9°) on the average. Compared with the proportion of patients with postoperative step-off of < 1 mm of posterior malleolar fracture, the proportion of patients with positive posttraumatic osteoarthritis at postoperative step-offs of 1-2 and > 2 mm was higher (P < 0.05), and the functions of the affected limbs were evidently degraded Olerud-Molander score, VAS score, and ankle dorsiflexion restriction; P < 0.05). However, the differences in the proportion of patients with positive posttraumatic osteoarthritis and functional prognosis between postoperative step-offs of 1-2 mm and > 2 mm were not statistically significant (P > 0.05). Posterior malleolar step-off was an independent, statistically significant risk factor for posttraumatic osteoarthritis (Wald = 14.23, P < 0.01), and both posterior malleolar step-off and posttraumatic osteoarthritis were independent risk factors that led to the poor functional prognosis (P < 0.05).

CONCLUSION: Clinically, importance should be given to the anatomical reduction of posterior malleolar fractures and the incidence of posttraumatic osteoarthritis to improve the long-term functional effects on affected limbs.

FUND PROGRAM: Natural Science Foundation of Xinjiang Uygur Autonomous Region（2024D01C11; Xinjiang Tianshan Talent Training Program (2023TSYCJC0053); Shanghai Science and Technology Commission Project (22S31900300, 21ZR1458500).

PMID:40819085 | DOI:10.1186/s12891-025-09050-8

BMC Health Serv Res. 2025 Aug 16;25(1):1088. doi: 10.1186/s12913-025-13121-w.

ABSTRACT

BACKGROUND: This study aims to examine unmet healthcare needs and the burden of out-of-pocket (OOP) payments in Bangladesh among hypertensive adults using the most recent survey data.

METHODS: A total of 5086 hypertensive patients aged 18 to 80 were recruited from 75 pharmacies in Bangladesh in 2023, 35 being located in urban areas and 40 in rural areas. Unmet healthcare needs was the primary outcome variable, while the incidence of catastrophic health expenditures (CHE) was the secondary outcome variable. A multilevel logistic regression model was performed to identify factors associated with unmet healthcare needs and CHE. A multilevel Tobit regression model was used to identify the determinants of OOP health expenditures.

RESULTS: The study indicated that the prevalence of unmet healthcare needs among hypertensive adults was around 26% and incidence of CHE was 46% at 10% threshold of total consumption in Bangladesh. The most common reason for unmet healthcare needs was affordability, long waiting times, lack of availability, and transportation issues etc. Unmet healthcare needs were more prevalent among men, individuals with no education, divorced/separated, non-Muslims and poor population. Regression models suggested that older people, men, those with higher education, Muslim, married people, larger household, overweight and obese people, and rural residents were more likely to burden of OOP expenses.

CONCLUSIONS: High unmet needs and CHE prevalence in Bangladesh reveal inadequate health risk protection. Prioritizing affordability, addressing disparities, and strengthening financial risk protection can improve access and outcomes for hypertensive adults.

PMID:40819056 | DOI:10.1186/s12913-025-13121-w

BMC Public Health. 2025 Aug 16;25(1):2795. doi: 10.1186/s12889-025-24048-6.

ABSTRACT

INTRODUCTION: The health of the elderly represents a critical public health concern that can be positively influenced by the adoption of health-promoting lifestyle behaviors. This quasi-experimental study aimed to evaluate the effectiveness of multimodal educational interventions in improving the lifestyle of older adults.

MATERIALS AND METHODS: This quasi-experimental intervention study was conducted with 118 eligible elderly participants recruited from health service centers in Qom, Iran. Data were collected using a two-part questionnaire comprising demographic information and the Health-Promoting Lifestyle Profile II (HPLP-II). The intervention group participated in eight 30-minute group sessions (organized into six groups), held twice weekly, covering topics such as nutrition, physical activity, stress management, and mental health. The control group did not receive any educational intervention during the study period. Two months following the completion of the educational program, the questionnaire was re-administered to both groups. Data were analyzed using SPSS version 21. Descriptive statistics were employed to summarize participant characteristics and study variables. Inferential analyses included Box’s M test to assess the homogeneity of variance-covariance matrices, as well as univariate and multivariate analyses of covariance (ANCOVA and MANCOVA), with the significance level set at 0.05.

FINDINGS: The mean scores for lifestyle dimensions-including health responsibility, physical activity, nutrition, stress management, interpersonal relationships, spiritual growth, and self-actualization-did not differ significantly between the intervention and control groups prior to the educational program. However, following the intervention, the mean scores in the intervention group increased significantly across all dimensions (p < 0.0001).

CONCLUSION: The findings indicate that the educational intervention had a positive effect on all six dimensions of lifestyle-related behaviors among the elderly.

PMID:40819050 | DOI:10.1186/s12889-025-24048-6

BMC Musculoskelet Disord. 2025 Aug 16;26(1):794. doi: 10.1186/s12891-025-09062-4.

ABSTRACT

BACKGROUND: Hip fractures are a significant public health issue among the elderly. While early surgical intervention’s effects on morbidity are well-documented, the impact of delayed surgery on mortality and morbidity is less understood. This study aims to examine the medium-term morbidity and mortality in patients who underwent delayed surgery with an average preoperative waiting period of 14 days.

MATERIALS: This retrospective study used data from hospital records, Social Security Institution death records, and telephone surveys. Included were patients aged 65 and older with femoral neck or pertrochanteric fractures. Excluded were those younger than 65, with pathological or subtrochanteric fractures, and without adequate preoperative and postoperative follow-up. Preoperative waiting time, mobilization status, ASA score, NLR, and mortality rates were recorded. Postoperative follow-ups occurred at 2, 6, and 12 weeks, 6 months, 1 year, and annually. Various statistical methods investigated the impact of preoperative waiting time on mortality and mobility.

RESULTS: A total of 289 hip fracture surgeries were followed for an average of 5.1 years (range: 0-8.5 years). The mean age was 79 (range: 65-100), with 174 females (60.2%) and 115 males (39.8%). The average preoperative waiting time was 14 days (range: 0-49 days). ROC analysis indicated the critical mortality threshold was 12 days. The one-month cumulative mortality rate was 6% for patients operated on within the first 12 days and 11% for those operated on after 12 days. One-year cumulative mortality rates were 21% for patients operated on within 12 days and 39% for those operated on after 12 days.

CONCLUSION: This study confirms the relationship between surgical delay and increased mortality rates in hip fracture patients, with a 12-day threshold for high mortality risk exceeding typical reports. While no statistically significant relationship was found between preoperative waiting time and ambulation, one-third of postoperative patients could walk without support and nearly half could not walk at all. Despite being retrospective, this study with a large patient population demonstrates the significant impact of surgical delay on mortality and morbidity rates in hip fracture patients.

PMID:40819048 | DOI:10.1186/s12891-025-09062-4