Category: Statistics

Biom J. 2025 Dec;67(6):e70092. doi: 10.1002/bimj.70092.

ABSTRACT

In clinical trials, patients may discontinue treatments prematurely, breaking the initial randomization. In our motivating study, a randomized controlled trial in oncology, patients assigned the investigational treatment may discontinue it due to adverse events. The ICH E9(R1) Addendum provides guidelines for handling such “intercurrent events.” The right strategy to adopt depends on the questions of interest. We propose adopting a principal stratum strategy and decomposing the overall intention-to-treat effect into principal causal effects for groups of patients defined by their potential discontinuation behaviour. We first show how to implement a principal stratum strategy to assess causal effects on a survival outcome in the presence of continuous-time treatment discontinuation, its advantages, and the conclusions that can be drawn. Our strategy allows us to properly handle the time-to-event intermediate variable, which is not defined for patients who would not discontinue, and to account for the fact that the discontinuation time and the primary endpoint are subject to censoring. We employ a flexible model-based Bayesian approach to tackle these complexities, providing easily interpretable results. We apply this Bayesian principal stratification framework to analyze synthetic data of the motivating oncology trial. Supported by a simulation study, we shed light on the role of covariates in this framework. Beyond making structural and parametric assumptions more credible, they lead to more precise inference. Also, they can be used to characterize patients’ discontinuation behavior, which could help inform clinical practice and future protocols.

PMID:41231435 | DOI:10.1002/bimj.70092

Biomarkers. 2025 Nov 13:1-15. doi: 10.1080/1354750X.2025.2589251. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies have identified that HOTAIR polymorphisms were expressed abnormally in a range of cancers, including breast, gastric, liver, and lung cancers. However, the impact of this gene on colorectal cancer (CRC) remains a topic of debate. To obtain the most accurate results, the association of HOTAIR polymorphisms with CRC risk was analyzed in this meta-analysis (MA).

METHODS: The PubMed, Embase, Cochrane, and Web of Science databases were searched to find the correlation of HOTAIR polymorphisms with CRC up to February 2024. The association of HOTAIR polymorphisms with CRC susceptibility was assessed using odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: Five relevant studies were identified in total. In all HOTAIR polymorphism studies involving CRC, it was found that the subgroup analysis by ethnicity revealed that the rs1899663 G > T codominant and dominant models were positively correlated with CRC development in Asian populations and negatively correlated with CRC development in non-Asian populations (Codominant: OR = 0.70, 95% CI = 0.39 – 1.25; D: Dominant: OR = 0.65, 95% CI = 0.28 – 1.53）.

CONCLUSIONS: This MA indicates that HOTAIR polymorphism-the rs1899663 G > T genotype-might have a racially specific impact on CRC risk.

PMID:41231428 | DOI:10.1080/1354750X.2025.2589251

Ir J Med Sci. 2025 Nov 13. doi: 10.1007/s11845-025-04171-4. Online ahead of print.

ABSTRACT

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment for selected peritoneal surface malignancies. However, postoperative hemodynamic fluctuations, fluid shifts, and nephrotoxic chemotherapeutic agents may increase the risk of acute kidney injury (AKI). Early postoperative lactate levels and lactate clearance are markers of tissue perfusion and metabolic recovery, but their prognostic role after HIPEC remains unclear.

AIMS: To evaluate the association between early postoperative lactate dynamics (0-h and 12-h lactate levels and lactate clearance) and AKI, defined by KDIGO criteria, in patients undergoing HIPEC. Secondary aims were to assess the relationship of lactate dynamics with ICU length of stay and mortality.

METHODS: This retrospective, single- center cohort included 98 patients who underwent CRS-HIPEC between 2019 and 2024. Demographic, perioperative, and postoperative data were collected. Lactate clearance was calculated from 0-h and 12-h lactate values. AKI was defined according to KDIGO criteria. Statistical comparisons and ROC curve analysis were performed, with p < 0.05 considered significant.

RESULTS: AKI occurred in 32.7% of patients. Intraoperative inotrope use was significantly associated with AKI. Patients with AKI had longer ICU length of stay and higher mortality. The 12-h lactate level was significantly higher in the AKI group and showed limited but significant predictive value for AKI (AUC = 0.623). A threshold above 1.9 mmol/L indicated higher risk. Elevated 12-h lactate and negative lactate clearance were also strong predictors of mortality.

CONCLUSION: Postoperative 12-h lactate was associated with AKI and strongly predicted mortality, whereas lactate clearance was not predictive of AKI. Elevated postoperative 12-h lactate and negative clearance may serve as simple and early biomarkers for risk stratification following HIPEC.

PMID:41231421 | DOI:10.1007/s11845-025-04171-4

Biom J. 2025 Dec;67(6):e70097. doi: 10.1002/bimj.70097.

ABSTRACT

Antitumor activity in oncology clinical trials is typically assessed using overall survival (OS) or progression-free survival (PFS) endpoints, which are often imprecise and uninformative in small, noncomparative studies. The tumor growth inhibition (TGI) model, which captures both drug effects and natural tumor growth, quantitatively characterizes tumor size dynamics as a function of drug dosage, offering a more informative framework for comparing cancer treatments. In this work, we study the locally optimal design for a comparative oncology trial in which Dalpiciclib is the investigational agent and Capecitabine is the reference drug under an active control (AC) setting. Our novel approach avoids unrealistic distributional assumptions about response measurements. The resulting locally AC-optimal design minimizes the variance of the estimated matching dose of Dalpiciclib to Capecitabine and may unify Phase II and Phase III objectives by allowing evaluation of a higher Dalpiciclib dose with prespecified superiority.

PMID:41231415 | DOI:10.1002/bimj.70097

Eur J Nucl Med Mol Imaging. 2025 Nov 13. doi: 10.1007/s00259-025-07631-2. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the relationship between [¹⁸F]PSMA-1007 PET parameters and biochemical recurrence-free survival (BCR-FS) in high-risk primary prostate cancer patients receiving neoadjuvant hormonal treatment.

METHODS: This prospective randomized, double-blind, placebo-controlled phase II trial included 89 high-risk primary prostate cancer patients who received a pelvic [¹⁸F]PSMA-1007 PET/MRI prior to and following neoadjuvant hormonal treatment. Patients were randomly assigned to neoadjuvant hormonal treatment with degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 3 months followed by radical prostatectomy and extended pelvic lymph node dissection. The following [¹⁸F]PSMA-1007 PET parameters were determined on the pre- and posttreatment [¹⁸F]PSMA-1007 PET: (i) semi-quantitative [¹⁸F]PSMA-1007 PET parameters such as SUV_max, SUV_mean, PSMA-expressing volume and total lesion activity, and their absolute and relative differences; (ii) number of pelvic lymph node, distant and extraprostatic (i.e. pelvic lymph node and distant) metastases determined on [¹⁸F]PSMA-1007 PET; (iii) [¹⁸F]PSMA-1007 PET-based response criteria (aPERCIST and RECIP 1.0); (iv) molecular imaging TNM-stage as determined by PROMISE V2.

RESULTS: 35% of included patients developed BCR within a median follow-up time of 38 months. Multivariate regression analyses revealed that PSMA-expressing volume posttreatment, the number of distant metastases pretreatment and miN1 + miN2 vs. miN0 pretreatment were significant predictors of BCR-FS with hazard ratios of 1.184 (95% CI 1.070-1.309, p = 0.0010), 5.820 (95% CI 2.498-13.561, p < 0.0001) and 4.024 (95% CI 1.740-9.307, p = 0.0011), respectively.

CONCLUSION: Our results indicate that [¹⁸F]PSMA-1007 PET might be used to aid in patient stratification for determining which patients would benefit from additional (neo)adjuvant treatment.

PMID:41231407 | DOI:10.1007/s00259-025-07631-2

Discov Ment Health. 2025 Nov 13;5(1):176. doi: 10.1007/s44192-025-00210-9.

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has had a profound impact on the mental health of medical workers worldwide. While extensive research has investigated pandemic-related mental health challenges, longitudinal analyses of temporal trends remain scarce. This study employs a cross-sectional design to compare mental health outcomes among medical workers in Beijing’s Mobile Cabin Hospitals during the Early-Pandemic Era (2020) and Post-Pandemic Era (2022), with a focus on occupational disparities.

METHODS: This study utilized a cross-sectional design to compare mental health outcomes among medical workers in Beijing’s Mobile Cabin Hospitals during two distinct pandemic phases. Data were collected through anonymized online surveys administered via Wenjuanxing. The questionnaire comprised three domains: demographic characteristics, professional roles within departments and the 12-item General Health Questionnaire (GHQ-12). Emotional distress was operationally defined as a GHQ-12 total score ≥ 4.

RESULTS: Comparative analysis revealed a significant deterioration in mental health outcomes among medical workers during the Post-Pandemic Era compared to the Early-Pandemic Era. The prevalence of emotional distress (GHQ-12 ≥ 4) remained elevated across specific subgroups: medical workers aged 30-39 years, married, working as doctors and other professionals. Statistically significant interphase differences emerged in vulnerable populations, including female (P < 0.001), unmarried (P = 0.004), worked with nurses (P = 0.003) and other professionals (P = 0.021), and aged less than 40 years (< 30 years old, P = 0.009; 30-39 years old, P = 0.021). Qualitative symptom profiling indicated that more people reported clinically meaningful manifestations of psychological distress, characterized by depressive symptoms, anxiety, diminished self-worth, and impaired coping capacity during adversity.

CONCLUSION: The cumulative burden of prolonged pandemic has demonstrably exacerbated mental health deterioration among medical workers. These findings underscore the critical need to sustainably safeguard the mental health of medical workers in future public health crises.

PMID:41231405 | DOI:10.1007/s44192-025-00210-9

Childs Nerv Syst. 2025 Nov 13;41(1):352. doi: 10.1007/s00381-025-07039-1.

ABSTRACT

PURPOSE: This study investigates normocephalic craniosynostosis (NC), a condition characterised by the premature fusion of cranial sutures without visible cranial deformities, which may be associated with significant neurodevelopmental risks.

METHODS: A case-control study was conducted involving patients aged 1 to 20 years with incidental diagnoses via CT scans. We collected comprehensive data from electronic medical records, including demographics, CT characteristics, neurological symptoms, and comorbidities.

RESULTS: The study included 42 NC cases and 41 controls with patent cranial sutures. The average cephalic index was 81.7% in NC cases and 81.2% in controls, with no significant difference (p = 0.44). The mean age at scanning was similar between groups (11.7 years for NC versus 11.3 years for controls, p = 0.29). Notably, a marked male predominance was observed among NC cases (83.3% versus 56.1% in controls, p = 0.01). Additionally, a history of abnormal neurological issues was more common in the NC group (35.7%) compared to 19.5% in controls. A family history of abnormal neurodevelopment was noted in 4.8% of NC cases and was absent in controls; however, the difference was not statistically significant (p = 0.08).

CONCLUSIONS: These findings underscore the possible pathological implications of NC, emphasising the need for enhanced clinical vigilance and thorough monitoring. A multidisciplinary approach is crucial in evaluating and managing these patients to ensure optimal care and enhance understanding of NC, despite the absence of external cranial deformities.

PMID:41231404 | DOI:10.1007/s00381-025-07039-1

Environ Monit Assess. 2025 Nov 13;197(12):1335. doi: 10.1007/s10661-025-14664-5.

ABSTRACT

The Bay of Cartagena, located in the Colombian Caribbean, suffers from significant pollution caused by urban, industrial, commercial, tourism, maritime, and port activities. Studies conducted since the 1970s have documented contamination by heavy metals such as Cu, Cr, Ni, and Zn, which are essential for living organisms due to their role in metabolic functions, but at excessive concentrations, they become toxic. From 2015 to 2019, within the framework of REDCAM, the metals Cr, Cd, Pb, Cu, Ni, and Zn were monitored in the Bay of Cartagena, finding that only 25% of the collected data were at quantifiable concentrations and the remaining 75% were below the laboratory’s quantification limits, which has hindered the determination of whether the contaminants are present or absent, leading to the reporting of censored data. This study aimed to propose an alternative analysis for these censored data using the regression on order statistics (ROS) model and to perform a temporal comparison of heavy metal concentrations in the Bay of Cartagena, thereby providing a more accurate assessment of its metal contamination status.

PMID:41231397 | DOI:10.1007/s10661-025-14664-5

J Adhes Dent. 2025 Nov 13;27:221-230. doi: 10.3290/j.jad.c_2336.

ABSTRACT

PURPOSE: To evaluate bonding to dentin contaminated with primers/etchants used for adjacent ceramic repair.

MATERIALS AND METHODS: Mid-coronal dentin of sound human third molars was exposed and allocated to 10 experimental groups. The universal adhesive (UA) Single Bond Universal (‘SBU,’ 3M Oral Care), applied either in etch-and-rinse (E&R) or self-etch (SE) bonding mode, and the considered gold-standard SE adhesive Clearfil SE Bond X (‘CSE,’ Kuraray Noritake) were bonded to dentin contaminated with either Monobond Etch & Prime (‘MEP,’ Ivoclar) or IPS Ceramic Etching Gel (‘HF,’ Ivoclar) following 10 scenarios: phosphoric acid (PA)+SBUE&R (uncontaminated E&R UA control), HF+PA+SBUE&R, MEP+PA+SBUE&R, PA+MEP+SBUE&R, SBUSE (uncontaminated SE UA control), HF+SBUSE, MEP+SBUSE, CSESE (uncontaminated SE control), HF+CSESE, MEP+CSESE. Upon adhesive and composite application, the specimens were stored in artificial saliva at 37°C. After 1 week, all specimens were sectioned into resin-bonded dentin sticks, which were randomly distributed over two groups to be subjected to a microtensile bond-strength test immediately at 1 week or upon aging by storage in artificial saliva for 6 months. Statistics involved linear mixed-effects modeling with Bonferroni correction (P 0.05).

RESULTS: E&R bonding to dentin contaminated with MEP or HF did not significantly differ from bonding to non-contaminated dentin (controls). However, SE bonding to MEP- and HF-contaminated dentin was significantly less effective than to non-contaminated dentin (controls). Aging for 6 months did not reduce E&R bonding as compared to the 1-week data, while SE bonding was significantly less effective upon 6-month aging. E&R bonding was affected more when dentin was contaminated with MEP before phosphoric acid (PA) etching than when dentin was contaminated with MEP after PA etching.

CONCLUSIONS: Dentin contamination with MEP and HF impacted self-etch (SE) bonding but not etch&rinse (E&R) bonding.

PMID:41231395 | DOI:10.3290/j.jad.c_2336

Int Urol Nephrol. 2025 Nov 13. doi: 10.1007/s11255-025-04906-3. Online ahead of print.

ABSTRACT

PURPOSE: Signet ring cell carcinoma (SRCC) of the urachus is a rare and aggressive histologic variant with limited guidance on optimal treatment. This study aimed to characterize the clinicopathological features, treatment patterns, and survival outcomes of urachal SRCC using a large national dataset and to assess the impact of surgical and systemic therapies on prognosis.

METHODS: We queried the National Cancer Database (NCDB) for patients diagnosed with urachal SRCC between 2004 and 2020. Clinical and pathological staging, surgical approach (partial vs. radical cystectomy), chemotherapy use, and overall survival were analyzed. Kaplan-Meier survival curves and statistical comparisons were used to evaluate treatment outcomes.

RESULTS: A total of 60 patients with SRCC of the urachus were identified. A substantial proportion presented with advanced or unstaged disease (43.3% cTX, 38.4% pTX). Partial cystectomy was performed more often than radical cystectomy (56.7% vs. 31.6%). Chemotherapy was administered in 38.4% of patients, most commonly as multi-agent regimens. Median overall survival was approximately 30 months. No significant survival benefit was observed with chemotherapy administration.

CONCLUSION: Urachal SRCC is associated with poor survival and considerable heterogeneity in staging and management. Our findings suggest limited observed benefit of systemic therapy in this cohort, underscoring the need for further prospective studies.

PMID:41231381 | DOI:10.1007/s11255-025-04906-3