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Ilana F Gareen,1,2 Bettina Siewert,3 David J Vanness,4 Benjamin Herman,2 CD Johnson,5 Constantine Gatsonis2,6 1Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA; 2Center for Statistical Sciences, Brown University School of Public Health, Providence, RI, USA; 3Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA; 4Population Health Sciences, University of Wisconsin, Madison, WI, USA; 5Mayo Clinic, Scottsdale, AZ, USA; 6Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA Background: Current American Cancer Society recommendations for colon cancer screening include optical colonoscopy every 10 years or computed tomography colonography (CTC) every 5 years. Bowel preparation (BP) is currently required for both screening modalities.Purpose: To compare ACRIN 6664: the National CT Colonography Trial (NCTCT) participant experiences with CTC and optical colonoscopy (OC), procedure preference, and willingness to return for each procedure.Materials and methods: Participants from fifteen NCTCT sites, who underwent CTC followed by OC under sedation, were invited to complete questionnaires 2 weeks postexam, asking about procedure preference, physical discomfort, and embarrassment experienced and whether that discomfort and embarrassment was better or worse than expected during BP, CTC, and OC, as well as willingness to return for repeat CTC and OC at different time intervals.Results: A total of 2,310 of 2,600 patients (89%) returned their questionnaires. Of patients reporting a preference, 1,058 (46.6%) preferred CTC, 569 (25.0%) preferred OC, and 626 (27.6%) reported no preference. Participant-reported discomfort worse than expected differed significantly between CTC (32.9%) and OC (5.0%) (P

PurposeTo assess the relative accuracies of computed tomography (CT) and magnetic resonance (MR) imaging in the local staging of primary malignant bone and soft-tissue tumors.Materials and methodsAt four institutions, 367 eligible patients (aged 6-89 years) with malignant bone or soft-tissue neoplasms in selected anatomic sites were enrolled. Patients underwent both CT and MR imaging within 4 weeks before surgery. In each patient, CT scans were interpreted independently by two radiologists and MR images by two other radiologists at the enrolling institution. The CT and MR images were then interpreted together by two of those radiologists and subsequently reread at the other institutions. Imaging and histopathologic findings were compared and were supplemented when needed with surgical findings. Receiver operating characteristic curve analysis and descriptive statistical analysis were performed.ResultsCases were analyzable in 316 patients: 183 had primary bone tumors; 133 had primary soft-tissue tumors. There was no statistically significant difference between CT and MR imaging in determining tumor involvement of muscle, bone, joints, or neurovascular structures. The combined interpretation of CT and MR images did not statistically significantly improve accuracy. Interreader variability was similar for both modalities.ConclusionCT and MR imaging are equally accurate in the local staging of malignant bone and soft-tissue neoplasms in the specific anatomic sites studied.

BACKGROUND: Numerous studies have documented substantial differences by race and gender in the use of coronary artery bypass graft surgery and percutaneous coronary angioplasty. However, few studies have examined whether these differences reflect problems in quality of care. METHOD: We selected a random sample stratified by gender, race, and income of 5026 Medicare beneficiaries aged 65 to 75 who underwent inpatient coronary angiography during 1991 to 1992 in 1 of 5 states. We compared the frequency of 2 problems in quality by race and gender: underuse or the failure to receive a clinically indicated revascularization procedure and receipt of revascularization when it was not clinically indicated. We used 2 independent sets of criteria developed by the RAND Corporation and the American College of Cardiology/American Hospital Association (ACC/AHA). We also examined survival of the cohort through March 31, 1994. RESULTS: Revascularization procedures were clinically indicated more frequently among whites than blacks and among men than women. Failure to receive revascularization when it was indicated was more common among blacks than among whites (40% vs. 23-24%, depending on the criteria, both P<0.001) but similar among men and women (25% vs. 22-24%, P>0.05). Racial disparities remained similar after adjusting for patient and hospital characteristics. Among patients rated inappropriate, use of procedures was greater for whites than blacks using RAND criteria (10.5% vs. 5.8%, P<0.01) and greater for men than for women (14.2% vs. 5.3% by RAND criteria, P=0.001; 8.2% vs. 4.0%% by ACC/AHA criteria, P=0.04). After multivariate adjustment, the disparities for race and gender remained similar and were statistically significant using RAND criteria. Mortality rates tended to validate our appropriateness criteria for underuse. CONCLUSIONS: Racial differences in procedure use reflect higher rates of clinical appropriateness among whites, greater underuse among blacks, and more frequent revascularization when it was not clinically indicated among whites. Underuse is associated with higher mortality. In contrast, men had higher rates of clinical appropriateness and were more likely to receive revascularization when it was not clinically indicated. There was no evidence of greater underuse among women. [ABSTRACT FROM AUTHOR]

We considered methods for transporting a prediction model for use in a new target population, both when outcome and covariate data for model development are available from a source population that has a different covariate distribution compared with the target population and when covariate data (but not outcome data) are available from the target population. We discuss how to tailor the prediction model to account for differences in the data distribution between the source population and the target population. We also discuss how to assess the model's performance (e.g., by estimating the mean squared prediction error) in the target population. We provide identifiability results for measures of model performance in the target population for a potentially misspecified prediction model under a sampling design where the source and the target population samples are obtained separately. We introduce the concept of prediction error modifiers that can be used to reason about tailoring measures of model performance to the target population. We illustrate the methods in simulated data and apply them to transport a prediction model for lung cancer diagnosis from the National Lung Screening Trial to the nationally representative target population of trial-eligible individuals in the National Health and Nutrition Examination Survey., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology., Objective: To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status., Design, Setting, and Participants: This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia-Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019. Data were analyzed from May to November 2020., Exposures: Amyloid detected in blood and by positron emission tomography (PET) imaging., Main Outcomes and Measures: The main outcome was the diagnostic performance of plasma Aβ42:40 ratio, together with apoE proteotype and age, for identifying amyloid PET status, assessed by accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC)., Results: All 686 participants (mean [SD] age 73.2 [6.3] years; 368 [53.6%] men; 378 participants [55.1%] with amyloid PET findings) had symptoms of mild cognitive impairment or mild dementia. The AUC of plasma Aβ42:40 ratio for PARIS was 0.79 (95% CI, 0.73-0.85) and 0.86 (95% CI, 0.82-0.89) for MissionAD. Ratio cutoffs for Aβ42:40 based on the Youden index were similar between cohorts (PARIS: 0.089; MissionAD: 0.092). A logistic regression model (LRM) incorporating Aβ42:40 ratio, apoE proteotype, and age improved diagnostic performance within each cohort (PARIS: AUC, 0.86 [95% CI, 0.81-0.91]; MissionAD: AUC, 0.89 [95% CI, 0.86-0.92]), and overall accuracy was 78% (95% CI, 72%-83%) for PARIS and 83% (95% CI, 79%-86%) for MissionAD. The model developed on the prospectively collected samples from PARIS performed well on the MissionAD samples (AUC, 0.88 [95% CI, 0.84-0.91]; accuracy, 78% [95% CI, 74%-82%]). Training the LRM on combined cohorts yielded an AUC of 0.88 (95% CI, 0.85-0.91) and accuracy of 81% (95% CI, 78%-84%). The output of this LRM is the Amyloid Probability Score (APS). For clinical use, 2 APS cutoff values were established yielding 3 categories, with low, intermediate, and high likelihood of brain amyloid plaque pathology., Conclusions and Relevance: These findings suggest that this blood biomarker test could allow for distinguishing individuals with brain amyloid-positive PET findings from individuals with amyloid-negative PET findings and serve as an aid for Alzheimer disease diagnosis.

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers ( 18 F-florbetapir/FBP, 18 F-florbetaben/FBB or 18 F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with the image as it is. We validate rPOP with n = 740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the Imaging Dementia-Evidence for Amyloid Scanning - Brain Health Registry sub-study (IDEAS-BHR) and n = 1,518 scans from the Alzheimer's Disease Neuroimaging Initiative (n = 1,249 FBP, n = 269 FBB), including heterogeneous acquisition and reconstruction protocols. After running rPOP, a standard quantification to extract Standardized Uptake Value ratios and the respective Centiloids conversion was performed. rPOP-based amyloid status (using an independent pathology-based threshold of ≥24.4 Centiloid units) was compared with either local visual reads (IDEAS-BHR, n = 663 with complete valid data and reads available) or with amyloid status derived from an MRI-based PET processing pipeline (ADNI, thresholds of >20/>18 Centiloids for FBP/FBB). Finally, within the ADNI dataset, we tested the linear associations between rPOP- and MRI-based Centiloid values. rPOP achieved accurate warping for N = 2,233/2,258 (98.9%) in the first pass. Of the N = 25 warping failures, 24 were rescued with manual reorientation and origin reset prior to warping. We observed high concordance between rPOP-based amyloid status and both visual reads (IDEAS-BHR, Cohen's k = 0.72 [0.7-0.74], ∼86% concordance) or MRI-pipeline based amyloid status (ADNI, k = 0.88 [0.87-0.89], ∼94% concordance). rPOP- and MRI-pipeline based Centiloids were strongly linearly related (R 2 :0.95, p<0.001), with this association being significantly modulated by estimated PET resolution (β= -0.016, p<0.001). rPOP provides reliable MRI-free amyloid-PET warping and quantification, leveraging widely available software and only requiring an attenuation-corrected amyloid-PET image as input. The rPOP pipeline enables the comparison and merging of heterogeneous datasets and is publicly available at https://github.com/leoiacca/rPOP., (Copyright © 2021. Published by Elsevier Inc.)

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of 1.3 (95% CI=0, 1.605). One thousand fifty participants from 44 sites were randomized to CCTA (n=518) or SPECT (n=532). Mean follow-up time was 16.2 (SD 7.9) months. There were no cardiac-related deaths. In patients with a negative CCTA there was 1 acute myocardial infarction; in patients with a negative SPECT examination there were 2 acute myocardial infarctions; and for positive CCTA and SPECT, 1 acute myocardial infarction each. Participants in the CCTA arm had a similar rate of MACE or revascularization compared with those in the SPECT myocardial perfusion imaging arm, (HR, 1.03; 95% CI=0.61-1.75) ( P =0.19). CCTA segment involvement by a stenosis of ≥50% diameter was a better predictor of MACE and revascularization at 1 year ( P =0.02) than the percent reversible defect size by SPECT myocardial perfusion imaging. Four (1.2%) patients with negative CCTA compared with 14 (3.2%) with negative SPECT had MACE or revascularization ( P =0.03). Conclusions There was no difference in outcomes of patients who had stable angina and who underwent CCTA in comparison to SPECT as the first imaging test directing them to optimal medical therapy alone or with revascularization. CCTA was a better predictor of MACE and revascularization. Registration Information URL: https://www.clinicaltrials.gov/. Identifier: NCT01262625.

Rationale: Annual computed tomography (CT) is now widely recommended for lung cancer screening in the United States, although concerns remain regarding the potential harms, including those from overdiagnosis., Objectives: To examine the effect of airflow limitation on overdiagnosis by comparing lung cancer incidence, histology, and stage shift in a subgroup of the National Lung Screening Trial (NLST)., Methods: In an NLST subgroup (n = 18,714), screening participants were randomized to annual computed tomography (CT, n = 9,357) or chest radiograph (n = 9,357) screening and monitored for a mean of 6.1 years. After baseline prebronchodilator spirometry, to identify the presence of airflow limitation, 18,475 subjects (99%) were assigned as having chronic obstructive pulmonary disease (COPD) or no COPD. Lung cancer prevalence, incidence, histology, and stage shift were compared after stratification by COPD., Measurements and Main Results: For screening participants with spirometric COPD (n = 6,436), there was a twofold increase in lung cancer incidence (incident rate ratio, 2.15; P < 0.001) and, when compared according to screening arm, no excess lung cancers and comparable histology. Compared with chest radiography, there was also a trend favoring reduced late-stage and increased early-stage cancers in the CT arm (P = 0.054). For those with normal baseline spirometry (n = 12,039), we found an excess of lung cancers during screening in the CT arm, almost exclusively early-stage adenocarcinoma-related cancers (histology shift and overdiagnosis). After correction for these excess cancers, stage shift was marginal (P = 0.077)., Conclusions: In the CT arm of the NLST-ACRIN (American College of Radiology Imaging Network) cohort, COPD status was associated with a doubling of lung cancer incidence, no apparent overdiagnosis, and a more favorable stage shift.

Unlabelled: We investigated the correlation between metabolic response by (18)F-FDG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib mesylate therapy., Methods: (18)F-FDG PET was performed at baseline, 1-7 d, and 4 or 8 wk after imatinib mesylate initiation. Best objective response was defined by version 1.0 of the Response Evaluation Criteria in Solid Tumors (RECIST). Mutational analysis and tumor GLUT4 expression by immunohistochemistry were done on tissue obtained at baseline or surgery., Results: (18)F-FDG PET showed high baseline tumor glycolytic activity (mean SUV(max), 14.2; range, 1.3-53.2), decreasing after 1 wk of imatinib mesylate (mean, 5.5; range, -0.5-47.7, P < 0.001, n = 44), and again before surgery (mean, 3.0; range, -0.5-36.1, P < 0.001, n = 40). At week 1, there were 3 patients with complete metabolic response (CMR), 33 with partial metabolic response (PMR), 6 with stable metabolic disease (SMD), and 2 with progressive metabolic disease (PMD). Before surgery, there were 3 with CMR, 33 with PMR, 4 with SMD, and none with PMD. The best response according to RECIST was 2 with partial response, 36 with stable disease, and 1 with progressive disease (n = 39). Of the patients with a posttreatment decrease in GLUT4 expression, 1 had CMR, 15 had PMR, 2 had SMD, and 1 had PMD at week 1, whereas before surgery 1 patient had CMR, 16 had PMR, 2 had SMD, and none had PMD. Among 27 patients with KIT exon 11 mutations, 1 had CMR, 22 had PMR, 3 had SMD, and 1 had PMD at week 1, whereas 1 had CMR, 22 had PMR, 2 had SMD, and 2 were unknown before surgery; among 4 patients with a wild-type genotype, 2 had PMR and 2 SMD at week 1, whereas 1 had CMR, 2 had PMR, and 1 had SMD before surgery., Conclusion: After imatinib mesylate initiation, metabolic response by (18)F-FDG PET was documented earlier (1-7 d) and was of much greater magnitude (36/44) than that documented by RECIST (2/39). Immunohistochemistry data suggest that GLUT4 may play a role in (18)F-FDG uptake in gastrointestinal stromal tumor, GLUT4 levels decrease after imatinib mesylate therapy in most patients with PMR, and the biologic action of imatinib mesylate interacts with glycolysis and GLUT4 expression. A greater than 85% metabolic response was observed as early as days 1-7 in patients with exon 11 mutations.

Binary test outcomes typically result from dichotomizing a continuous test variable, observable or latent. The effect of the threshold for test positivity on test sensitivity and specificity has been studied extensively in receiver operating characteristic (ROC) analysis. However, considerably less attention has been given to the study of the effect of the positivity threshold on the predictive value of a test. In this paper we present methods for the joint study of the positive (PPV) and negative predictive values (NPV) of diagnostic tests. We define the predictive receiver operating characteristic (PROC) curve that consists of all possible pairs of PPV and NPV as the threshold for test positivity varies. Unlike the simple trade-off between sensitivity and specificity exhibited in the ROC curve, the PROC curve displays what is often a complex interplay between PPV and NPV as the positivity threshold changes. We study the monotonicity and other geometric properties of the PROC curve and propose summary measures for the predictive performance of tests. We also formulate and discuss regression models for the estimation of the effects of covariates.

We propose methods for regression analysis of repeatedly measured ordinal categorical data when there is nonmonotone missingness in these responses and when a key covariate is missing depending on observables. The methods use ordinal regression models in conjunction with generalized estimating equations (GEEs). We extend the GEE methodology to accommodate arbitrary patterns of missingness in the responses when this missingness is independent of the unobserved responses. We further extend the methodology to provide correction for possible bias when missingness in knowledge of a key covariate may depend on observables. The approach is illustrated with the analysis of data from a study in diagnostic oncology in which multiple correlated receiver operating characteristic curves are estimated and corrected for possible verification bias when the true disease status is missing depending on observables.

We examined the cost of health care and out-of-pocket medical expenditures for 189 persons with AIDS at three sites in Massachusetts: an HMO; a public hospital immunodeficiency clinic; and a group practice at a major teaching hospital. The mean cost of care during a four-month reference period was $9,093 +/- $12,683 (mean +/- standard deviation) per patient. Thirty-six percent of the cost was due to hospital care and 40% was due to home health care. Mean out-of-pocket expenditures were $429 +/- $991 (mean +/- standard deviation). Studies that focus on the cost of hospital care may seriously underestimate the medical costs of AIDS.

Profiling provider performance for the assessment of quality involves a number of issues related to selection of appropriate quality measures, subsequent data collection and analysis, and selection of standards of comparison. This article emphasizes the limitations of current data systems for this purpose and discusses hierarchical modeling as the optimal analytic approach for analyzing resulting data. Mention is made of the difficulties of achieving large enough sample sizes for statistical significance at the individual provider level. Finally, the article discusses feasible options for profiling quality.