Category: Statistics

JCO Precis Oncol. 2025 Jul;9:e2500172. doi: 10.1200/PO-25-00172. Epub 2025 Jul 23.

ABSTRACT

PURPOSE: The surveillance protocol for early-stage non-small cell lung cancer (NSCLC) is not contingent upon individualized risk factors for recurrence. This study aimed to use comprehensive data from clinical practice to develop a deep-learning model for practical longitudinal monitoring.

METHODS: A multimodal deep-learning model with transformers was developed for real-time recurrence prediction using baseline clinical, pathological, and molecular data with longitudinal laboratory and radiologic data collected during surveillance. Patients with NSCLC (stage I to III) who underwent surgery with curative intent between January 2008 and September 2022 were included. The primary outcome was predicting recurrence within 1 year after the monitoring point. This study demonstrates the timely provision of risk scores (RADAR score) and determined thresholds and the corresponding AUC.

RESULTS: A total of 14,177 patients were enrolled (10,262 with stage I, 2,380 with stage II, and 1,703 with stage III). The model incorporated 64 clinical-pathological-molecular factors at baseline, along with longitudinal laboratory and computed tomography imaging interpretation data. The mean baseline RADAR score was 0.324 (standard deviation [SD], 0.256) in stage I, 0.660 (SD, 0.210) in stage II, and 0.824 (SD, 0.140) in stage III. The AUC for predicting relapse within 1 year of the monitoring point was 0.854 across all stages, with a sensitivity of 86.0% and a specificity of 71.3% (AUC = 0.872 in stage I, AUC = 0.737 in stage II, and AUC = 0.724 in stage III).

CONCLUSION: This pilot study introduces a deep-learning model that uses multimodal data from routine clinical practice to predict relapses in early-stage NSCLC. It demonstrates the timely provision of RADAR risk scores to clinicians for recurrence prediction, potentially guiding risk-adapted surveillance strategies and aggressive adjuvant systemic treatment.

PMID:40700672 | DOI:10.1200/PO-25-00172

J Eval Clin Pract. 2025 Aug;31(5):e70217. doi: 10.1111/jep.70217.

ABSTRACT

IMPORTANCE: Identifying how fraudulent practices affect quality performance metrics is crucial for enhancing healthcare delivery and maintaining the integrity of the Medicare system.

OBJECTIVE: To examine the association between fraud and abuse perpetrator providers (FAPs) and their performance on quality metrics within the Merit-Based Incentive Payment System (MIPS) under the Medicare Access and CHIP Reauthorization Act (MACRA).

DESIGN: A retrospective observational study using exact matching and propensity score matching to balance comparison groups.

SETTING: Analysis of Medicare Quality Payment Program (QPP) data from 2017 to 2021.

PARTICIPANTS: A total of 12,364 physician-year observations, including 1300 provider-year level FAPs identified between 2020 and 2023 and 11,064 matched non-FAPs.

EXPOSURES: Provider status as fraud and abuse perpetrators based on inclusion in the List of Excluded Individuals and Entities from the Office of Inspector General.

MAIN OUTCOMES AND MEASURES: MIPS scores across key categories: Final score, Quality score, Promoting Interoperability (PI) score, Improvement Activities (IA) score, and Cost score.

RESULTS: FAPs scored significantly lower than non-FAPs in Final score, Quality score, PI score, and IA score (all p < 0.05). The negative impact of FAP status was more pronounced among individual practitioners, while FAPs participating in Advanced Alternative Payment Models exhibited higher scores on certain metrics. No significant differences were observed in Cost scores between FAPs and non-FAPs.

CONCLUSIONS AND RELEVANCE: Fraudulent practices are associated with lower performance on quality-related metrics under MACRA’s MIPS framework, particularly among individual practitioners. While lower quality scores align with expectations for providers committing fraud, the absence of significant differences in Cost scores highlights potential shortcomings in the MIPS scoring system, suggesting that cost metrics may not be sufficiently sensitive to fraudulent practices. These findings underscore the need for continuous refinement of both quality and cost measures to enhance the integrity and effectiveness of healthcare delivery.

PMID:40700659 | DOI:10.1111/jep.70217

Biochemistry. 2025 Jul 23. doi: 10.1021/acs.biochem.5c00068. Online ahead of print.

ABSTRACT

A hallmark of neurodegenerative diseases like Alzheimer’s Disease (AD) and chronic traumatic encephalopathy (CTE) is the presence of toxic protein aggregates in neurons. In AD and CTE specifically, the protein tau forms insoluble fibrils that are hundreds of nanometers in length. Intriguingly, recent experimental structures suggest that tau ligands like the disaggregator EGCG and positron emission tomography (PET) tracers like GTP-1 and MK-6240 bind to tau fibrils in long stacks reflecting the symmetry of the protein across many binding sites. In these stacks, each ligand makes more contact with its symmetry mates than it does with the protein. To interpret the binding of these molecules and new ligands, we must understand the effects of the cooperativity between sites and the entropy coming from the number of sites. Here, we investigate a nearest-neighbors model of cooperativity and use statistical mechanics to derive binding isotherms for saturation and competition experiments. This model allows us to relate measured EC₅₀ and IC₅₀ values to the intrinsic binding affinity to a single site and to cooperativity across sites in ways resembling the Cheng-Prusoff Equation. Depending on the degree of cooperativity between molecular species, this model permits solutions that lack the steep binding curves expected from cooperative systems and even solutions resembling 2-site systems. We finally consider conditions for a fibril’s detection in a PET scan and practical matters of fitting this model’s parameters to data.

PMID:40700656 | DOI:10.1021/acs.biochem.5c00068

J Magn Reson Imaging. 2025 Jul 23. doi: 10.1002/jmri.70040. Online ahead of print.

ABSTRACT

BACKGROUND: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, and accurate assessment is required for diagnosis and management. Goldmann applanation tonometry (GAT) requires corneal contact, whereas non-contact tonometry (NCT) is susceptible to ocular geometry.

PURPOSE: To evaluate three-dimensional MR elastography (3D-MRE) as a non-invasive method for IOP assessment.

STUDY TYPE: Prospective.

SUBJECTS: Twenty-nine healthy volunteers (13 females and 16 males, median age: 33).

FIELD STRENGTH/SEQUENCE: Phase-contrast spin-echo echo planar MRE at 3.0 T.

ASSESSMENT: IOP measured by GAT (IOP_GAT) and NCT (IOP_NCT) was obtained. Ocular geometry parameters (central corneal thickness [CCT], mean keratometry [Km], axial length [AL], anterior chamber depth [ACD], and lens thickness [LT]) were measured by optical biometry. The first 10 subjects underwent repeated MRE at 60, 90, and 120 Hz to assess test-retest repeatability, and 90 Hz was used in subsequent acquisitions. Three readers (S.Y., G.Z., and Z.Y., with 12, 3, and 3 years of experiences in MRE, respectively) independently assessed shear stiffness (SS) of the anterior segment and whole eye to evaluate test-retest repeatability and inter-/intra-observer agreement.

STATISTICAL TESTS: Wilcoxon signed rank test; multivariable regression; intraclass correlation coefficient (ICC); Spearman’s correlation; Significance level: p < 0.05.

RESULTS: SS@90 Hz of the anterior segment (SS-AS@90 Hz) demonstrated excellent repeatability and inter-/intra-observer agreement (all ICC ≥ 0.889). IOP_GAT demonstrated a stronger correlation with SS-AS@90 Hz (r = 0.64) than with IOP_NCT (r = 0.59). Multivariable regression identified SS-AS@90 Hz (β = 0.53) and IOP_NCT (β = 0.40) as independent predictors of IOP_GAT, collectively explaining 58.3% of the variance. No correlation between SS-AS@90 Hz and CCT (p = 0.10), Km (p = 0.67), ACD (p = 0.90), or LT (p = 0.82) was found, while a significant correlation with AL (r = 0.02) was observed.

DATA CONCLUSION: SS-AS@90 Hz was identified as a robust biomarker for predicting IOP, independent of most ocular geometric parameters.

EVIDENCE LEVEL: 1.

TECHNICAL EFFICACY: 1.

PMID:40700641 | DOI:10.1002/jmri.70040

Clin Exp Dent Res. 2025 Aug;11(4):e70185. doi: 10.1002/cre2.70185.

ABSTRACT

OBJECTIVES: Destructive carious lesions on deciduous teeth often result in dental abscesses. Sometimes, the exudative process may extend to the dental follicle of the permanent tooth, leading to various types of consequences. This study primarily seeks to determine the prevalence of developmental defects of enamel (DDE) in premolars whose predecessors developed endodontic abscesses. Furthermore, it investigates how the prevalence of DDE is influenced by the type of treatment the affected deciduous molar received. Lastly, the study compares the prevalence of DDE between maxillary and mandibular premolars.

MATERIAL AND METHODS: Demographics, medical and dental history, and records of DDE were extracted from the medical records of 1164 pediatric patients. DDE of 107 premolars from patients who had experienced abscesses in their deciduous molars were compared to DDE of 107 premolars from patients who naturally shed healthy deciduous molars. DDE were also compared between different treatment modalities and anatomical regions. Fisher’s exact tests were used to compare groups, while demographic data were analyzed by descriptive statistics and reported as mean ± standard deviation or as median and interquartile range for the continuous variables.

RESULTS: Compared to premolars whose predecessors did not exhibit signs of pathology, those that developed endodontic abscesses reported a higher prevalence of DDE (57% vs. 17.8%; OR 6.14; p < 0.0001). Endodontic treatment on deciduous molars was associated with higher DDE prevalence compared to surgical treatment (70.2% vs. 46.7%; OR 2.69; p = 0.016). Maxillary premolars showed a higher prevalence of DDE compared to mandibular premolars (75.4% vs. 24.6%; OR 5.23; p = 0.00008).

CONCLUSIONS: Chronic endodontic abscess on deciduous molars significantly increases the risk of DDE in the corresponding premolars. ET on deciduous molars is associated with higher incidence of DDE compared to extraction. Maxillary premolars are more likely to develop DDE than mandibular premolars.

PMID:40700621 | DOI:10.1002/cre2.70185

Oncologist. 2025 Jul 23:oyaf225. doi: 10.1093/oncolo/oyaf225. Online ahead of print.

ABSTRACT

Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate comprised of a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2, a protein that is broadly expressed in several types of solid tumors. In the TROPION-Lung01 phase III trial (NCT04656652), Dato-DXd demonstrated statistically significant improvement in median progression-free survival (mPFS) over docetaxel (4.4 vs. 3.7 months, hazard ratio [HR]=0.75, 95% confidence interval [CI], 0.62-0.91, P=.004]) in patients with previously treated metastatic non-small cell lung cancer (mNSCLC). Improvement in PFS was demonstrated in patients with nonsquamous mNSCLC (mPFS: 5.5 vs. 3.6 months, HR = 0.63, 95% CI, 0.51-0.79) and those with NSQ mNSCLC and actionable genomic alterations (mPFS: 5.7 vs 2.6 months, HR = 0.35, 95% CI, 0.21-0.60). A pooled analysis of previously treated patients with epidermal growth factor receptor mutation-positive NSCLC from TROPION-Lung01 and TROPION-Lung05 (NCT04484142) treated with Dato-DXd supported clinical activity (mPFS: 5.8 months, 95% CI, 5.4-8.2). In the TROPION-Breast01 phase III trial (NCT05104866), Dato-DXd demonstrated statistically significant improvement in mPFS over the investigator’s choice of chemotherapy (6.9 vs. 4.9 months, HR = 0.63, 95% CI, 0.52-0.76, P<.0001) in patients with previously treated post-endocrine therapy hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Dato-DXd also demonstrated a distinct safety profile in both trials. The successful implementation of any new anticancer therapy requires learning how to prevent, monitor, and manage treatment-related adverse events (AE). Information can be gained from real-world clinical practices, institutional approaches, and multidisciplinary teams who treat patients with Dato-DXd to provide a better patient experience and improved outcomes. Here, we discuss practical insights and management and treatment of key AEs from Dato-DXd, including oral mucositis/stomatitis, nausea and vomiting, ocular surface events, and interstitial lung disease garnered from a multidisciplinary team of health care professionals experienced in treating patients with Dato-DXd.

PMID:40700616 | DOI:10.1093/oncolo/oyaf225

Oncologist. 2025 Jul 23:oyaf224. doi: 10.1093/oncolo/oyaf224. Online ahead of print.

ABSTRACT

BACKGROUND: Biliary tract cancer is a rare tumour entity mostly diagnosed at advanced stages with poor prognosis. Since publication of the TOPAZ-1-trial, durvalumab + gemcitabine/cisplatin has become the standard palliative first-line treatment. However, real-world evidence is inconclusive and no systematic review or meta-analysis has yet evaluated the current available literature on this topic.This meta-analysis therefore aimed to assess the effectiveness of durvalumab plus gemcitabine/cisplatin as first-line treatment compared to the previous standard and evaluate the existing evidence of this treatment in real-world cohorts.

METHODS: Trials investigating durvalumab + gemcitabine/cisplatin as palliative first-line treatment in advanced biliary tract cancer and published in PubMed/Medline databases between January 2020 and December 2024 were included. Studies on second line treatment or studies investigating other than the standard chemotherapy backbones were excluded. Selection of the trials and quality assessment was conducted independently by two reviewers. Trials with a two-arm design reporting effect measures were included in the meta-analysis.

RESULTS: After screening 190 studies, 10 trials encompassing 2877 patients were included. Evidence was heterogeneous but results of the meta-analysis demonstrated a statistically significant difference in overall survival and progression free survival, in favor of patients treated with durvalumab + gemcitabine/cisplatin.

CONCLUSION: This systematic review and meta-analysis confirms durvalumab + gemcitabine/cisplatin as best currently available treatment option in patients with advanced biliary tract cancer. Furthermore, multiple real-world cohorts reported similar results even in patients with higher risk factors. However, trials are heterogeneous and further evidence from real-world cohorts is needed to enhance data quality.

PMID:40700609 | DOI:10.1093/oncolo/oyaf224

Integr Environ Assess Manag. 2025 Jul 23:vjaf093. doi: 10.1093/inteam/vjaf093. Online ahead of print.

ABSTRACT

Pollinating bee dietary risk assessment for pesticide registration requires knowledge of nectar and pollen pesticide residue concentrations following different pesticide application methods to crops. The magnitude and duration of bee dietary pesticide exposures vary according to crop attractiveness to bees, physio-chemical properties, plant characteristics, application rate, method, and timing, and soil characteristics. Regulatory authorities rely on model-generated default estimates of pollinator exposure when measured food item pesticide residue data are unavailable for pesticide active ingredients. In North America, default pesticide residue estimates for pollen and nectar are imbedded in the United States Environmental Protection Agency’s BeeREX model and, depending on the application method, are derived from various model approaches and data sources. Pursuing comprehensive bee-relevant data, we compiled and analyzed pesticide residue data from nectar and pollen samples collected during numerous field studies previously submitted to the United States Environmental Protection Agency, California Department of Pesticide Regulation, Canada Pesticide Regulatory Agency, and the European Food Safety Authority by pesticide product registrants. The information was compiled into a database that is accessible through an interactive Excel® user interface termed NPRUDv1. The interactive file that makes up NPRUDv1 allows the user to generate statistical estimates of pesticide residue per unit dose (RUD) values in nectar and pollen matrices for different application methods. The values can be used to calculate nectar and pollen estimated environmental concentrations (EECs) in models to assess dietary pollinator risk. The use of this database and the NPRUDv1 tool will strengthen the dietary exposure component of pollinator pesticide risk assessments by utilizing a database of field-measured pollen and nectar residue concentrations that represent pesticide use patterns in different crops. This publication describes the procedures followed to establish a globally comprehensive nectar and pollen residue database, demonstrates the use of NPRUDv1 and demonstrates its applicability to lower tier pollinator pesticide risk assessment.

PMID:40700598 | DOI:10.1093/inteam/vjaf093

Br J Radiol. 2025 Jul 23:tqaf170. doi: 10.1093/bjr/tqaf170. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effectiveness and safety of transcatheter arterial embolization (TAE) with N-butyl-2 Cyanoacrylate (NBCA) versus without NBCA for the treatment of iatrogenic renal hemorrhage (IRH) in patients with normal coagulation profiles.

METHODS: Forty-nine participants with normal coagulation profiles were divided into two groups: NBCA (n = 12) and non-NBCA (n = 37). The primary outcome assessed was the primary clinical success rate, with secondary analyses conducted on technical success rate, secondary clinical success rate, procedure duration and cost, angiographic results, and adverse events.

RESULTS: Patients exhibited a near-normal coagulation condition (98.4%, 50/51). Technical success was attained in all patients, with no statistically significant differences observed between primary clinical success rate (p > 0.99), secondary clinical success rate (p > 0.99), procedure time (p = 0.469), and surgical costs (p = 0.057) when comparing the sides. In the non-NBCA group, negative angiographic findings were more prevalent compared to the NBCA group (43.2% vs 0, p = 0.012). No significant differences were found in serum creatinine and urea levels before and after treatment in both groups (p > 0.05). Minor complications were observed after the TAE procedure, with a higher percentage in the NBCA group compared to the non-NBCA group (p = 0.088).

CONCLUSIONS: TAE has been shown to be a safe and effective treatment for IRH in patients with normal coagulation conditions, regardless of the use of N-butyl cyanoacrylate (NBCA) glue.

ADVANCES IN KNOWLEDGE: There were no significant differences in procedure time or costs between the NBCA group and other treatment modalities. However, these findings require validation in large-scale randomized controlled trials.

PMID:40700592 | DOI:10.1093/bjr/tqaf170

Br J Radiol. 2025 Jul 23:tqaf172. doi: 10.1093/bjr/tqaf172. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aims to compare apparent diffusion coefficient (ADC) findings between leiomyosarcoma (LMS) and atypical/degenerate leiomyoma (LM) and evaluate the usefulness of this biomarker for diagnosis. Additionally it will explore the potential of preoperative neutrophil lymphocyte ratio (NLR) as a haematological marker to aid in the differentiation of LMS from atypical LM.

METHODS: Histologically proven LMS and LM patients between 2013-2023 were included. For all patients (191 LM, 18 LMS), the pre-operative full blood count was analysed, and the NLR calculated. Whole volume of interest (VOI) and focal region of interest (ROI) areas were manually segmented on patients with DW-MRI sequences available (52 LM, 12 LMS). Mann-Whitney and Fishers exact test were used to assess statistical significance and ROC curves for diagnostic performance.

RESULTS: VOI and ROI mean ADC values were significantly lower for LMS than LM, with ROI mean ADC demonstrating greater diagnostic accuracy (AUC 0.817 vs 0.755). Applying a threshold ROI mean ADC value of ≤ 1.00 x10-3 mm2/sec achieved a sensitivity and specificity of 88.3% and 65.4% respectively. A higher NLR was suggestive of LMS (median 2.8 vs 1.7 for LM).

CONCLUSIONS: ADC, particularly a focal ROI is useful in differentiating LMS from LM. Differences in preoperative blood markers, suggest an inflammatory-malignancy relationship. Future risk stratification models of ADC and haematological parameters should be explored.

ADVANCES IN KNOWLEDGE: This study adds to few studies comparing using both ROI and VOI based methods, and no study has assessed both haematological markers and ADC metrics to aid differentiation.

PMID:40700586 | DOI:10.1093/bjr/tqaf172