Mihai Giurcanu

We propose non-parametric estimators of the hazard ratio for comparing two survival curves using estimating equations defined in terms of group-specific cumulative hazard functions. We first describe the methods and their asymptotic properties in the case of a constant hazard ratio. We then extend the methods and the asymptotic results when the hazard ratio is time dependent and well approximated by a locally constant function. We propose a method to select the change points in the local hazard ratios. We extend the methods to stratified estimators and propose tests for heterogeneity of constant and time-dependent hazard ratios across strata. In a simulation study, we describe the finite sample properties of the proposed estimators and compare their performance with the Cox partial maximum likelihood estimator (MLE) in terms of efficiency and accuracy of coverage rates. An example is provided to illustrate an application of the proposed methods in practice.

This study demonstrates that hybrid multidimensional MRI has the potential to improve MRI/US fusion biopsy results, provide more reliable detection of prostate cancer, and add complementary information to Prostate Imaging and Reporting Data System–based evaluation by expert radiologists.

Background and Objectives Trials of acute secondary prevention after minor stroke or transient ischemic attack (TIA), such as SOCRATES, POINT, and THALES, demonstrate a high initial rate of recurrence after ischemic events that drop quickly to a lower rate, suggesting a transient vulnerable clinical state, which may call for different treatments than the subsequent stabilized state. A kinetic model incorporating vulnerable and stabilized states provides estimates of the distinct kinetic rates reflecting the temporal features of underlying stroke mechanisms. We aimed to compare these kinetic rates between treatments and across trials, asking whether these features point to common pathophysiologic processes underlying stroke recurrence, and inform the targeting and timing of enhanced antiplatelet therapy in recurrent stroke prevention. Methods Kaplan-Meier recurrence-free survival curves in the SOCRATES, POINT, and THALES trials were estimated for each treatment group and fitted by nonlinear regression to the 2-state kinetic model, producing estimates of kinetic parameters, with standard errors estimated using the nonparametric bootstrap with repetitive resampling. Results For each trial, the 2-state kinetic model fit the survival curves better than did the null (single-state) kinetic model or the Weibull model (p < 0.05). Recurrence rates in the vulnerable state (k₁) were 100-fold higher than in the stabilized state (k₂). Transition rates from the vulnerable to stabilized state (k₀) were still more rapid. Kinetic parameters were consistent across the trials, without significant differences between the trials. Enhanced antiplatelet regimens produced significant reductions in k₁ (aspirin alone: 0.030 ± 0.004 d⁻¹; active treatment: 0.016 ± 0.003 d⁻¹; p < 0.01) but did not affect k₀ or k₂, suggesting that active treatment only affected risk in the vulnerable state. Modeling based on these kinetic parameters suggests that most of the benefit of active treatment occurred within 3 days. Discussion Across multiple trials of acute secondary prevention after minor stroke or TIA, recurrence of stroke is well-described by a 2-state kinetic model postulating vulnerable and stabilized states, with similar kinetic parameters across trials. Enhanced antiplatelet regimens only affected the recurrence rates in the vulnerable state, over a brief period. This analysis suggests that 2 distinct states follow acute cerebral ischemic events, subject to differential impact of immediate or delayed therapies.

Background: The objective of this study was to create normative growth curves for pediatric upper airway volume using 3D computed tomography with emphasis on the neonatal age group. Methods: We completed a single-institution, retrospective review of all patients with available CT scans between the ages of 0 and 60 months. Patients were excluded if they exhibited any maxillofacial dysmorphism or upper airway pathology or if scans showed the presence of airway appliances or tubes. 3D volumetric upper airway analysis was performed and 2D cephalometric measurements and growth parameters including height, weight and age were recorded for all patients. Linear regression analysis was used to develop a prediction model for airway volume in terms of age adjusting for cephalometric and growth parameters stratified by sex and the resulting model was used to create separate percentile curves for each sex group. Results: The growth curves were created based on CT scans from 217 healthy patients. Mean airway volume was significantly larger in males than females (3.23 ± 1.98 mm³ vs 2.61 ± 1.64 mm³, p = 0.017). Conclusions: Normative growth curves for neonatal and pediatric upper airway volume are a useful tool for tracking changes in airway volume in the growing infant.

Hybrid multidimensional MRI had similar or improved reader performance, higher interobserver agreement, and faster interpretation time for a diversely experienced group of radiologists diagnosing c... Background Variability of acquisition and interpretation of prostate multiparametric MRI (mpMRI) persists despite implementation of the Prostate Imaging Reporting and Data System (PI-RADS) version ...

To assess the necessity of endorectal coil use in 3 Tesla (T) prostate magnetic resonance imaging (MRI), a literature review comparing the image quality and diagnostic performance with an endorectal coil (ERC) and a without endorectal coil (NERC), with a phased array coil or a wearable perineal coil (WPC), was performed. A PubMed search of 3T prostate MRI using an endorectal coil for studies published until 31 July 2021 was performed. A total of 14 studies comparing 3T prostate MRI with and without endorectal coil use were identified. The quality scores and diagnostic performances were recorded for each study. In total, five studies compared image quality; five studies compared quality and performance; and four studies compared performance of detection, size of detected lesions, accuracy of cancer localization, and aggressiveness/staging. The use of an endorectal coil improved image quality with a higher overall signal to noise ratio, posterior and peripheral zone signal to noise ratio, high b-value attenuation diffusion coefficient (ADC) signal to noise ratio, and contrast to noise ratio. Endorectal coil use improved subjective image quality for anatomic detail on T2 weighted images (T2WI) and diffusion weighted images (DWI). Endorectal coil use had less motion artifact on DWI than non-endorectal coil use, but produced a higher occurrence of other artifacts on DWI. Endorectal coils had higher sensitivity, specificity, and positive predictive value (PPV) in the detection of overall and index lesions, as well as smaller and less aggressive lesions, missing fewer and smaller lesions than non-endorectal coils. Endorectal coils had higher sensitivity than non-endorectal coils in localizing and staging lesions. Endorectal coils improved quantitative and qualitative image quality and diagnostic performance in the detection of smaller and less aggressive cancers in 3T prostate MRI.

Purpose During the initial 12 months of the pandemic, racial and ethnic disparities in COVID-19 death rates received considerable attention but it has been unclear whether disparities in death rates were due to disparities in case fatality rates (CFRs), incidence rates or both. We examined differences in observed COVID-19 case fatality rates (CFRs) between U.S. Whites, Blacks/African Americans and Latinx during this period. Methods Using data from the COVID Tracking Project (CTP) and the CDC’s COVID-19 Case Surveillance Public Use dataset, we calculated CFR ratios comparing minority groups to Whites, both overall and separately by age group. We also used a model of monthly COVID-19 deaths to estimate CFR ratios, adjusting for age, gender, and differences across states and time. Results Overall Blacks and Latinx had lower CFRs than Whites. However, when adjusting for age, Blacks and Latinx had higher CFRs than Whites among those younger than 65. CFRs varied substantially across states and time. Conclusions Disparities in COVID-19 case fatality among U.S. Blacks and Latinx under age 65 were evident during the first year of the pandemic. Understanding racial/ethnic differences in COVID-19 CFRs is challenging due to limitations in available data.

We propose a nonparametric estimate of the scale-change parameter for characterizing the difference between two survival functions under the accelerated failure time model using an estimating equation based on restricted means. Advantages of our restricted means based approach compared to current nonparametric procedures is the strictly monotone nature of the estimating equation as a function of the scale-change parameter, leading to a unique root, as well as the availability of a direct standard error estimate, avoiding the need for hazard function estimation or re-sampling to conduct inference. We derive the asymptotic properties of the proposed estimator for fixed and for random point of restriction. In a simulation study, we compare the performance of the proposed estimator with parametric and nonparametric competitors in terms of bias, efficiency, and accuracy of coverage probabilities. The restricted means based approach provides unbiased estimates and accurate confidence interval coverage rates with efficiency ranging from 81% to 95% relative to fitting the correct parametric model. An example from a randomized clinical trial in head and neck cancer is provided to illustrate an application of the methodology in practice.