Tag: pubmed

Stat Med. 2025 Sep;44(20-22):e70262. doi: 10.1002/sim.70262.

ABSTRACT

With the advent of precision medicine and targeted therapies in cancer, new challenges in the statistical design of clinical trials have naturally emerged. Most randomized clinical trial designs incorporating predictive biomarkers (those associated with treatment efficacy) assume biomarkers are dichotomous, or dichotomize naturally continuous biomarkers upfront, or find cut points mid-way through the trial to classify patients as biomarker-positive or biomarker-negative. However, these practices ignore or discard information about continuous and possible nonlinear or non-monotone prognostic or predictive effects. In this article, we propose a novel adaptive enrichment trial design to handle continuous biomarkers with any effect shape, including Bayesian marker-adaptive randomization. We demonstrate that this design can correctly make marker-specific trial decisions with high efficiency, resulting in improved performance and patient-centered decisions compared to adaptive cut-point selection approaches without adaptive randomization that further ignore or oversimplify true underlying marker relationships.

PMID:40947424 | DOI:10.1002/sim.70262

Foot Ankle Int. 2025 Sep 14:10711007251361122. doi: 10.1177/10711007251361122. Online ahead of print.

ABSTRACT

BACKGROUND: The indications for deltoid ligament (DL) repair in ankle fractures with widened medial clear space (MCS) remain controversial. Many authors report no difference in long-term functional outcomes, whereas others report persistent MCS widening and higher malreduction rates without DL repair. This study compares DL repair to no repair exclusively in surgically treated bimalleolar equivalent Weber C fibula fractures.

METHODS: This was a retrospective chart review of surgically treated Weber C lateral malleolus fractures with syndesmosis stabilization, with associated DL injury (bimalleolar equivalent). Patients with associated posterior or medial malleolus fractures, Weber B or A fractures, fibula fixation constructs other than plate and screws, follow-up less than 12 months, and revisions were excluded. Those meeting the inclusion criteria were split into 2 groups: DL repair vs no repair. Collected data included patient demographics, surgical procedures performed, and outcome measures. Primary outcomes measured postoperative oblique MCS and valgus talar tilt angle (TTA). Secondary outcomes included fracture union, complications, and patient-reported outcome measures (PROMs).

RESULTS: Seventy-seven fractures were included; 48 underwent DL repair whereas 29 did not. The mean follow-up was 28.9 months. Most study outcomes within each group had a statistically significant postoperative improvement. The valgus TTA in the repair vs no repair groups was 0.1 ± 0.9 vs 1.3 ± 2.0 degrees, respectively (P < .001). The MCS in the repair vs no repair groups was 3.5 ± 0.6 vs 3.8 ± 1.3 mm, respectively (P = .169). There were statistically significant differences in favor of DL repair in postoperative Veterans RAND-12 Item Health Survey physical subscale (P = .025) and Foot and Ankle Ability Measure activities of daily living subscale (P = .044) scores. There were no complications or revision surgeries directly related to DL repair.

CONCLUSION: The DL repair group had superior functional outcomes and ankle coronal plane alignment in comparison to no repair. There were no complications or revisions related directly to the deltoid repair. These results support consideration of DL repair in bimalleolar equivalent Weber C ankle fractures to improve functional outcomes and coronal plane alignment.

PMID:40947422 | DOI:10.1177/10711007251361122

Stat Med. 2025 Sep;44(20-22):e70261. doi: 10.1002/sim.70261.

ABSTRACT

Neurodegenerative diseases such as Alzheimer’s and Parkinson’s often exhibit complex, multivariate longitudinal outcomes that require advanced statistical methods to comprehensively evaluate treatment efficacy. The Longitudinal Rank Sum Test (LRST) offers a nonparametric framework to assess global treatment effects across multiple longitudinal endpoints without requiring multiplicity corrections. This study develops a robust methodology for power and sample size estimation specific to the LRST, integrating theoretical derivations, asymptotic properties, and practical estimation techniques under large sample conditions. Validation through numerical simulations demonstrates the accuracy of the proposed methods, while real-world applications to clinical trials in Alzheimer’s disease (AD) and Parkinson’s disease (PD) highlight their practical significance. This framework facilitates the design of efficient, well-powered trials, advancing the evaluation of treatments for complex diseases with multivariate longitudinal outcomes.

PMID:40947402 | DOI:10.1002/sim.70261

Dent Mater. 2025 Sep 13:S0109-5641(25)00761-4. doi: 10.1016/j.dental.2025.09.003. Online ahead of print.

ABSTRACT

OBJECTIVES: The study evaluated the influence of digital design software on crown morphology, occlusal characteristics, fracture force, and marginal fit across varying preparation designs for an identical target tooth.

METHODS: A resin-based tooth (tooth 36) was digitized, manufactured (n=8), individually prepared and re-digitized. Five design groups were established using conventional software proposals, technician designs, two AI-based software solutions, and natural tooth-based reference designs. All systems employed consistent parameters. Crown designs were digitally assessed using quantitative morphological and occlusal metrics in reference to the original tooth. Crowns were milled, marginal fit was measured via digital microscopy, and fracture resistance was determined after thermal cycling and mechanical loading.

RESULTS: Morphological metrics revealed statistically significant deviations across groups, with the technician design achieving the best performance. Occlusal metrics showed high deviations in the positional accuracy of the contact points across all groups. Technician and AI-based designs exhibited comparable functional results. None of the design groups were able to achieve contact with all relevant antagonist teeth, due to high deviations in the mesiolingual cusp. Conventional software designs exhibited the lowest fracture forces. Significant improvements were achieved through technician intervention. Vertical marginal discrepancies remained comparable across groups.

SIGNIFICANCE: Improved functional and morphological design combined with high fracture resistance can reduce the need for clinical adjustments, minimize wear, and enhance crown longevity. Digital design software significantly influences crown morphology, occlusal characteristics and fracture forces. Vertical marginal discrepancies remain similar. AI-driven approaches demonstrate comparability with technician designs in terms of fracture forces, functional performance, and marginal fit.

PMID:40947383 | DOI:10.1016/j.dental.2025.09.003

Clin Colorectal Cancer. 2025 Aug 20:S1533-0028(25)00072-6. doi: 10.1016/j.clcc.2025.08.004. Online ahead of print.

ABSTRACT

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) status has been proposed as a biomarker to identify colorectal cancer (CRC) patients suitable for anti-HER2 treatment. However, response varies from HER2-negative CRC, influenced by factors such as the tumors immune microenvironment (TIME) in HER2-positive CRC patients. We aimed to characterize the TIME of HER2-positive CRC by assessing the associations of inflammatory cells and prognosis.

METHODS: TIME was characterized through immunostaining for CD3, CD4, CD8, CD20, CD68, Forkhead box protein P3 (Foxp3), and programmed death-ligand 1 (PD-L1) cell densities in 36 HER2-positive and 72 HER2-negative CRC patients. HER2 positivity was evaluated by the HERACLES criteria. PD-L1 expression was evaluated by the tumor proportion score (TPS) and combined proportion score (CPS).

RESULTS: In our study, the densities of CD3, CD4, CD8, CD20, CD68, Foxp3 cells and PD-L1 expression showed no statistic differences in HER2-positive CRC patients compared to HER2-negative patients. There was a greater proportion of Foxp3+ cells (≥ 10%) among patients with HER2-positive CRC (P = .023). Although the PD-L1 CPS was correlated with sex (P = .012), inflammatory cells and the PD-L1 TPS were not correlated with clinicopathological parameters. Additionally, CRC patients with PD-L1 CPSs ≥ 1 had significantly better event-free survival (EFS) than patients with PD-L1 CPSs < 1 (P = .029). For patients with HER2-positive CRC, higher CD68 indicated better EFS (P = .047).

CONCLUSIONS: This study characterized a preliminary immune microenvironment profile and indicated CD68 increased correlation with EFS for HER2-positive CRC patients. These immune microenvironment profiles and prognostic implications could serve as potential biomarkers for stratifying patients with HER-2 positive for clinical trials.

PMID:40947372 | DOI:10.1016/j.clcc.2025.08.004

Heart Lung. 2025 Sep 13:S0147-9563(25)00182-7. doi: 10.1016/j.hrtlng.2025.08.007. Online ahead of print.

ABSTRACT

BACKGROUND: DeepSeek is a recently launched large language model (LLM), whereas GPT-4o is an advanced ChatGPT version whose electrocardiography (ECG) interpretation capabilities have been previously studied. However, DeepSeek’s performance in this domain remains unexplored.

OBJECTIVES: This study aims to evaluate DeepSeek’s accuracy in ECG interpretation and compare it with GPT-4o, emergency medicine specialists, and cardiologists. A secondary aim is to assess any performance changes in GPT-4o over one year.

METHODS: Between February 9 and March 1, 2025, 40 ECG images (20 daily routine, 20 more challenging) from the book 150 ECG Cases were evaluated by both GPT-4o and DeepSeek, each model tested 13 times. The accuracy of their responses was compared with previously collected answers from 12 cardiologists and 12 emergency medicine specialists. GPT-4o’s 2025 performance was compared to its 2024 results on identical ECGs.

RESULTS: GPT-4o outperformed DeepSeek with higher median correct answers on daily routine (14 vs. 12), more challenging (13 vs. 10), and total ECGs (27 vs. 22) with statistically significant differences (p=0.048, p<0.001, p<0.001). A moderate agreement was observed between the responses provided by GPT-4o (p<0.001, Fleiss Kappa=0.473), while a substantial agreement was observed in the responses provided by DeepSeek (p<0.001, Fleiss Kappa=0.712). No significant year-over-year improvement was observed in GPT-4o’s performance.

CONCLUSION: This first evaluation of DeepSeek in ECG interpretation reveals its performance is lower than that of GPT-4o and human experts. While GPT-4o demonstrates greater accuracy, both models fall short of expert-level performance, underscoring the need for caution and further validation before clinical integration.

PMID:40947358 | DOI:10.1016/j.hrtlng.2025.08.007

Clin Breast Cancer. 2025 Aug 20:S1526-8209(25)00240-X. doi: 10.1016/j.clbc.2025.08.012. Online ahead of print.

ABSTRACT

INTRODUCTION: Advancements in health technologies have enabled the performance of minimally invasive procedures using ionizing radiation for radioscopy and fluoroscopy by various physicians including orthopedic surgeons, radiologists, urologists, cardiologists, vascular surgeons, and plastic surgeons. Simultaneously, there appears to be an increasing frequency of breast cancer among these professionals. In addition to other risk factors to which they are exposed, ionizing radiation plays a role in carcinogenesis. This study is a systematic review and meta-analysis conducted to summarize the available literature on breast cancer risk among female physicians occupationally exposed to ionizing radiation.

METHODS: A systematic search was conducted in the PubMed, Embase, and LILACS databases, as well as reference lists based on PRISMA checklist (PROSPERO CRD42024553635). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed at Review Manager.

RESULTS: Six observational studies were included, evaluating 34,744 participants: 8103 exposed to ionizing radiation and 26,641 controls, with a minimum 10-year follow-up. According to the NOS, 5 studies were classified as high quality and one as moderate. The meta-analysis revealed an increased breast cancer risk among female physicians exposed to ionizing radiation, with an odds ratio (OR) 1.84 (95% CI 1.11-3.06). A sensitivity analysis excluding the study classified as moderate quality showed a breast cancer risk in the exposed group with an OR 1.42 (95% CI 1.06-1.89).

CONCLUSIONS: Based on the results of this meta-analysis, female physicians occupationally exposed to ionizing radiation have an increased risk of breast cancer compared to those who are not exposed.

PMID:40947332 | DOI:10.1016/j.clbc.2025.08.012

J Pediatr Urol. 2025 Sep 1:S1477-5131(25)00459-0. doi: 10.1016/j.jpurol.2025.08.031. Online ahead of print.

ABSTRACT

PURPOSE: To study the outcomes, risk factors, and timing of fistula recurrence after surgical repair of urethrocutaneous fistula (UCF) in children with hypospadias.

METHODS: 102 patients with a complete follow-up (>5 months) who had a fistula repair after hypospadias surgery were retrospectively analyzed (2000-2023). Median (IQR) age and follow-up were 3.5 years (2-6) and 26 months (12-57), respectively. Analyzed data included demographics; type of hypospadias, urethroplasty and fistula repair; fistula characteristics, and complications.

STATISTICAL ANALYSIS: Mann-Whitney U, Fisher’s exact, and Chi-square tests.

RESULTS: The 2-year fistula recurrence rate was 23.5 %. Significant risk factors for secondary fistula recurrence after repair included: fistula size of 2-4 mm, previous fistula repair performed at another center, and the total number of fistula recurrences. Fistula repair using a skin flap was associated with a lower rate of recurrence. The median (IQR) and mean time to fistula recurrence were 10 (5.5-40) and 30 months respectively. Fistula recurrence occurred in 54.2 % within the first 12 months post-surgery and in 45.8 % after 12 months. No significant differences were observed regarding the type of hypospadias, the technique used for hypospadias repair, single-stage versus two-stage surgery, postoperative complications (including meatal stenosis and urethral strictures), fistula characteristics (location and number), or different surgeons performing the hypospadias and fistula repairs.

CONCLUSION: The risk of secondary fistula recurrence increased with a fistula size of 2-4 mm and the total number of recurrences. Using a skin flap reduced the recurrence rate. We recommend a minimum follow-up of 12 months, as nearly 50 % of recurrences occur in the medium-to long-term.

PMID:40947320 | DOI:10.1016/j.jpurol.2025.08.031

Pharmacoepidemiol Drug Saf. 2025 Sep;34(9):e70217. doi: 10.1002/pds.70217.

ABSTRACT

BACKGROUND: Assessing medication safety in the pediatric population can take many forms, but given the shortcomings of traditional methods, there has been a shift toward leveraging real-world data to bolster these efforts.

OBJECTIVES: To characterize demographics, enrollment, and health characteristics among pediatric members in the Sentinel Distributed Database (SDD).

METHODS: Using administrative healthcare data from the SDD between January 1, 2000, and May 8, 2023, we used descriptive statistics to characterize the demographics, enrollment, and select health characteristics of pediatric members in the following age groups: 29 days-< 24 months (infants), 2-< 6 years (young children), 6 -< 12 years (older children), 12-< 18 years (early adolescents), and 18-21 years (late adolescents).

RESULTS: Older children (6-< 12 years of age) represented the largest pediatric age group in the SDD, with over 46 million members, though there were between 27.5 and 45.4 million members in each of the other age groups as well. Estimates of common health conditions and medication use were in line with current national estimates.

CONCLUSIONS: The FDA’s Sentinel Distributed Database accurately captures key aspects of pediatric health and can be used as an adjunct to current methods to assess and monitor the safety of approved medical products in the pediatric United States population.

PMID:40947306 | DOI:10.1002/pds.70217

Pediatr Obes. 2025 Sep 14:e70055. doi: 10.1111/ijpo.70055. Online ahead of print.

ABSTRACT

BACKGROUND: Overweight/obesity among children under five is a growing global concern, especially in low- and middle-income countries (LMICs), yet consolidated evidence of this burden remains limited, which is crucial to target interventions. This review synthesises data from community-based studies to estimate the overall and individual pooled prevalences of overweight/obesity in this population and explores the factors associated.

METHODOLOGY: PubMed, Scopus and EMBASE were searched and screened for eligible studies published between April 2014 and 2024 individually by two researchers. Quality assessment of the eligible studies was conducted using the Joanna Briggs Institute (JBI) tool. Data regarding the prevalence of overweight, obesity and their associated factors, including maternal education, area of residence, maternal body weight, household incomes and breastfeeding practices, as reported in these included studies, were extracted. A random-effect model was used for the meta-analysis, and heterogeneity was evaluated using I² statistics. Sources of heterogeneity were explored through subgroup analyses comparing effect sizes across categories of geographic regions, overweight/obesity measurement guidelines, sample sizes and publication years. Meta-regression assessed the relationship between these variables and the pooled estimates.

RESULTS: Of the 13 734 studies screened, 21 were eligible for inclusion. The pooled prevalence of overweight/obesity among the under-five children in LMICs was 8.57% (95% confidence interval (CI) 5.24-12.63, I² 100% at p value < 0.01) with significant heterogeneity. Overnutrition prevalence increased from 7.43% during the 5 years of 2014-2018 to 9.12% during 2019-2023. The pooled prevalence of overweight/obesity varied significantly across geography, with the highest prevalence in the African region (17%) and the lowest in the Southeast Asian region (3.41%). Across the four studies that reported maternal education, children of mothers with secondary school education or higher had increased odds of having overweight/obesity [Odds Ratio (OR) (95% CI): 1.51 (1.21-1.88)]. Prevalence estimates also differed significantly by gender, with 6.89% for under-five boys and 4.75% for girls [OR (95% CI): 1.48 (1.08-2.04)]. Although individual studies reported significant associations with other factors such as area of residence, maternal body weight, income status and breastfeeding practices, a meta-analysis could not be performed due to heterogeneity.

CONCLUSION: Trends in childhood overnutrition in LMICs are concerning, with overall prevalence approaching estimates of those reported in a few high-income nations. Geographic variability, gender disparity and association with maternal education emphasise the need for region-specific policies, focusing on community engagement and awareness towards rising overnutrition.

PMID:40947305 | DOI:10.1111/ijpo.70055