Summary Competing risks arise naturally in time-to-event studies. In this article, we propose time-dependent accuracy measures for a marker when we have censored survival times and competing risks. ...Time-dependent versions of sensitivity or true positive (TP) fraction naturally correspond to consideration of either cumulative (or prevalent) cases that accrue over a fixed time period, or alternatively to incident cases that are observed among event-free subjects at any select time. Time-dependent (dynamic) specificity (1-false positive (FP)) can be based on the marker distribution among event-free subjects. We extend these definitions to incorporate cause of failure for competing risks outcomes. The proposed estimation for cause-specific cumulative TP/dynamic FP is based on the nearest neighbor estimation of bivariate distribution function of the marker and the event time. On the other hand, incident TP/dynamic FP can be estimated using a possibly nonproportional hazards Cox model for the cause-specific hazards and riskset reweighting of the marker distribution. The proposed methods extend the time-dependent predictive accuracy measures of Heagerty, Lumley, and Pepe (2000, Biometrics 56, 337-344) and Heagerty and Zheng (2005, Biometrics 61, 92-105).
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, INZLJ, IZUM, KILJ, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK, ZRSKP
Summary
Because osteoporosis is under-recognized in patients with vertebral fractures, we evaluated characteristics associated with osteoporosis identification. Most patients with vertebral fractures ...did not receive evaluation or treatment for osteoporosis. Black, younger, and male participants were particularly unlikely to have had recognized osteoporosis, which could increase their risk of negative outcomes.
Introduction
Vertebral fractures may be identified on imaging but fail to prompt evaluation for osteoporosis. Our objective was to evaluate characteristics associated with clinical osteoporosis recognition in patients who had vertebral fractures detected on their thoracolumbar spine imaging reports.
Methods
We prospectively identified individuals who received imaging of the lower spine at primary care clinics in 4 large healthcare systems who were eligible for osteoporosis screening and lacked indications of osteoporosis diagnoses or treatments in the prior year. We evaluated characteristics of participants with identified vertebral fractures that were associated with recognition of osteoporosis (diagnosis code in the health record; receipt of bone mineral density scans; and/or prescriptions for anti-osteoporotic medications). We used mixed models to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).
Results
A total of 114,005 participants (47% female; mean age 65 (interquartile range: 57–72) years) were evaluated. Of the 8579 (7%) participants with vertebral fractures identified, 3784 (44%) had recognition of osteoporosis within the subsequent year. In adjusted regressions, Black participants (OR (95% CI): 0.74 (0.57, 0.97)), younger participants (age 50–60: 0.48 (0.42, 0.54); age 61–64: 0.70 (0.60, 0.81)), and males (0.39 (0.35, 0.43)) were less likely to have recognized osteoporosis compared to white participants, adults aged 65 + years, or females.
Conclusion
Individuals with identified vertebral fractures commonly did not have recognition of osteoporosis within a year, particularly those who were younger, Black, or male. Providers and healthcare systems should consider efforts to improve evaluation of osteoporosis in patients with vertebral fractures.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A major biomedical goal associated with evaluating a candidate biomarker or developing a predictive model score for event-time outcomes is to accurately distinguish between incident cases from the ...controls surviving beyond t throughout the entire study period. Extensions of standard binary classification measures like time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves have been developed in this context (Heagerty, P. J., and others, 2000. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 56, 337-344). We propose a direct, non-parametric method to estimate the time-dependent Area under the curve (AUC) which we refer to as the weighted mean rank (WMR) estimator. The proposed estimator performs well relative to the semi-parametric AUC curve estimator of Heagerty and Zheng (2005. Survival model predictive accuracy and ROC curves. Biometrics 61, 92-105). We establish the asymptotic properties of the proposed estimator and show that the accuracy of markers can be compared very simply using the difference in the WMR statistics. Estimators of pointwise standard errors are provided.
Cancer patients, chronic kidney disease patients, and subjects infected with HIV are routinely monitored over time using biomarkers that represent key health status indicators. Furthermore, ...biomarkers are frequently used to guide initiation of new treatments or to inform changes in intervention strategies. Since key medical decisions can be made on the basis of a longitudinal biomarker, it is important to evaluate the potential accuracy associated with longitudinal monitoring. To characterize the overall accuracy of a time‐dependent marker, we introduce a summary ROC curve that displays the overall sensitivity associated with a time‐dependent threshold that controls time‐varying specificity. The proposed statistical methods are similar to concepts considered in disease screening, yet our methods are novel in choosing a potentially time‐dependent threshold to define a positive test, and our methods allow time‐specific control of the false‐positive rate. The proposed summary ROC curve is a natural averaging of time‐dependent incident/dynamic ROC curves and therefore provides a single summary of net error rates that can be achieved in the longitudinal setting.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
ROC curves are a popular method for displaying sensitivity and specificity of a continuous diagnostic marker, X, for a binary disease variable, D. However, many disease outcomes are time dependent, ...D(t), and ROC curves that vary as a function of time may be more appropriate. A common example of a time-dependent variable is vital status, where D(t) = 1 if a patient has died prior to time t and zero otherwise. We propose summarizing the discrimination potential of a marker X, measured at baseline (t = 0), by calculating ROC curves for cumulative disease or death incidence by time t, which we denote as ROC(t). A typical complexity with survival data is that observations may be censored. Two ROC curve estimators are proposed that can accommodate censored data. A simple estimator is based on using the Kaplan-Meier estimator for each possible subset X > c. However, this estimator does not guarantee the necessary condition that sensitivity and specificity are monotone in X. An alternative estimator that does guarantee monotonicity is based on a nearest neighbor estimator for the bivariate distribution function of (X, T), where T represents survival time (Akritas, M. J., 1994, Annals of Statistics 22, 1299-1327). We present an example where ROC(t) is used to compare a standard and a modified flow cytometry measurement for predicting survival after detection of breast cancer and an example where the ROC(t) curve displays the impact of modifying eligibility criteria for sample size and power in HIV prevention trials.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
Abstract Background and aims In previous analyses, we identified three dietary patterns from food frequency questionnaire data among a sample of Yup'ik Alaska Native people living in Southwest ...Alaska: a “subsistence foods” dietary pattern and two market-based dietary patterns “processed foods” and “fruits and vegetables”. In this analysis, we aimed to characterize the association between the dietary patterns and cardiometabolic (CM) risk factors (lipids, blood pressure, glucose, adiposity). Methods and results We used multilevel linear regression to estimate the mean of each CM risk factor, comparing participants in the 4th to the 1st quartile of each dietary pattern (n = 637). Models were adjusted for age, sex, past smoking, current smoking, and physical activity. Mean log triglyceride levels were significantly higher among participants in the 4th compared to the 1st quartile of the processed foods dietary pattern (β = 0.11). Mean HbA1c percent was significantly lower (β = −0.08) and mean diastolic blood pressure (DBP) mm Hg was significantly higher (β = 2.87) among participants in the 4th compared to the 1st quartile of the fruits and vegetables dietary pattern. Finally, mean log triglyceride levels and mean DBP mm Hg were significantly lower among participants in the 4th compared to the 1st quartile of the subsistence foods dietary pattern (β = −0.10 and β = −3.99 respectively). Conclusions We found increased CM risk, as reflected by increased triglycerides, associated with eating a greater frequency of processed foods, and reduced CM risk, as reflected by lower triglycerides and DBP, associated with eating a greater frequency of subsistence foods.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Epidural steroid injections may offer little-to-no short-term benefit in the overall population of patients with symptomatic spinal stenosis compared with lidocaine alone. We investigated whether ...imaging could identify subgroups of patients who might benefit most.
A secondary analysis of the Lumbar Epidural Steroid Injections for Spinal Stenosis prospective, double-blind trial was performed, and patients were randomized to receive an epidural injection of lidocaine with or without corticosteroids. Patients (
= 350) were evaluated for qualitative and quantitative MR imaging or CT measures of lumbar spinal stenosis. The primary clinical end points were the Roland-Morris Disability Questionnaire and the leg pain numeric rating scale at 3 weeks following injection. ANCOVA was used to assess the significance of interaction terms between imaging measures of spinal stenosis and injectate type on clinical improvement.
There was no difference in the improvement of disability or leg pain scores at 3 weeks between patients injected with epidural lidocaine alone compared with corticosteroid and lidocaine when accounting for the primary imaging measures of qualitative spinal stenosis assessment (interaction coefficients for disability score, -0.1; 95% CI, -1.3 to 1.2;
= .90; and for the leg pain score, 0.1; 95% CI, -0.6 to 0.8;
= .81) or the quantitative minimum thecal sac cross-sectional area (interaction coefficients for disability score, 0.01; 95% CI, -0.01 to 0.03;
= .40; and for the leg pain score, 0.01; 95% CI, -0.01 to 0.03;
= .33).
Imaging measures of spinal stenosis are not associated with differential clinical responses following epidural corticosteroid injection.
Contexte
: Il existe peu de recherches sur l’efficacité à long terme des injections péridurales de corticostéroïdes (IPC) chez les personnes âgées, malgré la prévalence élevée des douleurs au dos et ...au membre inférieur dans ce groupe d’âge. Nous avons testé les hypothèses selon lesquelles les adultes plus âgés recevant une IPC, comparés aux patients n’en recevant pas : 1) présentent avant l’IPC une douleur et une impotence fonctionnelle plus graves et une qualité de vie moindre (« critères cliniques ») ; 2) présentent une amélioration des critères cliniques après l’IPC et 3) sont améliorés grâce à un effet spécifique de l’IPC.
Méthodes
: Nous avons étudié prospectivement des patients de plus de 65 ans consultant en soins primaires dans trois systèmes de santé étatsuniens (registre BOLD), pour nouvel épisode de lombalgie. Les critères de jugement étaient l’intensité de la douleur du/des membre(s) inférieur(s) et lombaire, l’impotence fonctionnelle et la qualité de vie, évalués au départ et lors des suivis à 3, 6, 12 et 24 mois. Nous avons classé les participants comme suit : groupe 1, IPC dans les six mois suivant la visite de référence (
n
= 295) ; groupe 2, pas d’IPC dans les six mois (
n
= 4 809) ; groupe 3, pas d’IPC dans les six mois, appariés sur score de propension au groupe 1 (
n
= 483). Nous avons analysé les données au moyen d’une régression linéaire avec équations d’estimation généralisées.
Résultats
: L’intensité de la douleur, l’impotence fonctionnelle et la qualité de vie au départ étaient significativement plus défavorables chez les patients IPC (groupe 1) que chez ceux du groupe 2. L’amélioration entre l’initiation et le 24
e
mois de tous les critères était statistiquement significative dans le groupe 1. Cependant, aucune différence statistiquement significative n’a été observée entre les trajectoires des critères des groupes 1 et 3, appariés sur score de propension.
Conclusions
: Les personnes âgées traitées par IPC présentent une amélioration à long terme. Cependant, il est peu probable que cette amélioration soit le résultat d’un effet spécifique de l’IPC.
Importance
: Dans ce grand suivi prospectif de deux ans chez des sujets âgés présentant un nouvel épisode de lombalgie, la douleur lombaire et la douleur du/des membre(s) inférieur(s), l’impotence fonctionnelle et la qualité de vie ont évolué favorablement après IPC ; toutefois, l’appariement sur score de propension a montré que cette amélioration n’était probablement pas due à un effet spécifique des injections, ce qui indique que les corticostéroïdes en péridural sont peu susceptibles de procurer des bénéfices à long terme aux sujets âgés présentant un nouvel épisode de douleur lombaire et de douleur du/des membre(s) inférieur(s).
Multiple case series of vertebroplasty outcomes have been published, though no large, placebo controlled trial has yet been performed. Our aim was to report baseline characteristics for the ...Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), a randomized blinded controlled study of vertebroplasty.
We compared baseline demographics, pain scores, and scores on the modified Roland-Morris Disability Scale (RMDS), a back pain-specific metric, between 2 groups. One group included subjects enrolled at the lead INVEST site (n = 27 to date). The second group consisted of eligible patients seen concurrently at the lead INVEST site, who declined enrollment (n = 70). Comparisons were made by using 2-sample t tests.
Mean ages were similar between groups, averaging approximately 74 years among study participants and 77 years among nonenrolled eligible patients (P = .17). Approximately 75% of subjects were female in both groups. RMDS scores of enrolled patients at the lead site (18.0 +/- 4.2) were not statistically different from those of eligible nonenrolled patients at the lead site (18.6 +/- 3.6, P = .49). Pain scores in the enrolled subjects were measured as "average intensity over the prior 24 hours" with mean scores of 7.6 +/- 2.1 among enrolled patients at the lead site. Pain scores in eligible nonenrolled patients were measured as "pain at rest," with mean score of 3.4 +/- 3.3, and "pain with activity," with mean score of 8.5 +/- 2.0.
Patient demographics among subjects enrolled in the INVEST are similar to those in a cohort of eligible nonenrolled patients. Back pain-specific disability was similar between subjects enrolled in the INVEST study and eligible nonenrolled patients at the lead site.
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