Biomedical subjects

David Faraggi

Publications and source records attributed to David Faraggi.

9 recordsLinked to original sources

PubMed2006

ROC analysis for markers with mass at zero.

The receiver operating characteristic (ROC) curve and in particular the area under the curve (AUC) is commonly used to examine the discriminatory ability of diagnostic markers. Certain markers while basically continuous and non-negative have a positive probability mass (spike) at the value zero. We discuss a flexible modelling approach to such data and contrast it with the standard non-parametric approach. We show how the modelling approach can be extended to take account of the effect of explanatory variables. We motivate this problem and illustrate the modelling approach using data on the coronary calcium score, measured by electron beam tomography, which is a marker for atherosclerosis.

Adult↗

PubMed2006

Comparing the areas under two correlated ROC curves: parametric and non-parametric approaches.

In order to compare the discriminatory effectiveness of two diagnostic markers the equality of the areas under the respective Receiver Operating Characteristic Curves is commonly tested. A non-parametric test based on the Mann-Whitney statistic is generally used. Weiand et al. (1989) present a parametric test based on normal distributional assumptions. We extend this test using the Box-Cox power family of transformations to non-normal situations. These three test procedures are compared in terms of significance level and power by means of a large simulation study. Overall we find that transforming to normality is to be preferred. An example of two pancreatic cancer serum biomarkers is used to illustrate the methodology.

Area Under Curve↗

PubMed2005

Estimation of the Youden Index and its associated cutoff point.

The Youden Index is a frequently used summary measure of the ROC (Receiver Operating Characteristic) curve. It both, measures the effectiveness of a diagnostic marker and enables the selection of an optimal threshold value (cutoff point) for the marker. In this paper we compare several estimation procedures for the Youden Index and its associated cutoff point. These are based on (1) normal assumptions; (2) transformations to normality; (3) the empirical distribution function; (4) kernel smoothing. These are compared in terms of bias and root mean square error in a large variety of scenarios by means of an extensive simulation study. We find that the empirical method which is the most commonly used has the overall worst performance. In the estimation of the Youden Index the kernel is generally the best unless the data can be well transformed to achieve normality whereas in estimation of the optimal threshold value results are more variable.

Algorithms↗

PubMed2004

Reduced glomerular filtration rate in asymptomatic diabetic patients: predictor of increased risk for cardiac events independent of albuminuria.

OBJECTIVES: This study aimed to investigate the prevalence of a reduced glomerular filtration rate (GFR) with and without albuminuria and its ability to predict cardiac events in asymptomatic diabetic patients undergoing stress-rest thallium-201 myocardial perfusion single-photon emission computed tomography. BACKGROUND: Diabetic patients have a higher prevalence of asymptomatic coronary heart disease. Therefore, identifying predictors of cardiac events in asymptomatic diabetic patients is needed. METHODS: In 269 asymptomatic patients, baseline evaluation included diabetes-related complications, including creatinine clearance (CrCl) and albuminuria. During follow-up (mean 2.3 +/- 1.0 years), all cardiac events were recorded. RESULTS: Seventy-seven patients (29%) had a reduced GFR defined by CrCl <60 ml/min/1.73 m(2). Compared with the 177 patients with CrCl >/=60 ml/min/1.73 m(2), the reduced GFR group was older (p < 0.0001), had a longer duration of diabetes (p = 0.002), and had a higher prevalence of albuminuria (p = 0.04). Nevertheless, 35% of the reduced GFR group had normoalbuminuria. Patients with reduced GFR had a significant two-fold increase in total cardiac events (unstable angina, nonfatal myocardial infarction, and cardiac procedures) (25% vs. 13%, p = 0.019), and multivariate analysis found that reduced GFR was an independent predictor of cardiac events (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1 to 4.46). Other independent predictors of cardiac events included stress-induced abnormal myocardial perfusion imaging (OR 3.1, 95% CI 1.3 to 7.5), an electrocardiographic ischemic response (OR 2.7, 95% CI 1.01 to 7.14), and peripheral artery disease (OR 2.1, 95% CI 1.05 to 4.23); however, albuminuria was not. CONCLUSIONS: A reduced GFR was common in our group of asymptomatic diabetic patients and was associated with a two-fold increase in cardiac events. Multivariate analysis found that reduced GFR independent of albuminuria was a significant predictor of cardiac events.

Aged↗

PubMed2004

Adjusting the generalized ROC curve for covariates.

Receiver operating characteristic (ROC) curves and in particular the area under the curve (AUC), are widely used to examine the effectiveness of diagnostic markers. Diagnostic markers and their corresponding ROC curves can be strongly influenced by covariate variables. When several diagnostic markers are available, they can be combined by a best linear combination such that the area under the ROC curve of the combination is maximized among all possible linear combinations. In this paper we discuss covariate effects on this linear combination assuming that the multiple markers, possibly transformed, follow a multivariate normal distribution. The ROC curve of this linear combination when markers are adjusted for covariates is estimated and approximate confidence intervals for the corresponding AUC are derived. An example of two biomarkers of coronary heart disease for which covariate information on age and gender is available is used to illustrate this methodology.

Adult↗

PubMed2003

ROC curve analysis for biomarkers based on pooled assessments.

Interleukin-6 is a biomarker of inflammation which has been suggested as having potential discriminatory ability for myocardial infarction. Because of its high assaying cost it is very expensive to evaluate this marker. In order to reduce this cost we propose pooling the specimens. In this paper we examine the efficiency of ROC curve analysis, specifically the estimation of the area under the ROC curve, when dealing with pooled data. We study the effect of pooling when there are only a fixed number of individuals available for testing and pooling is carried out to save on the number of assays. Alternatively we examine how many pooled assays of size g are necessary to provide essentially the same information as N individual assays. We measure loss of information by means of the change in root mean square error of the estimate of the area under the ROC curve and study the extent of this loss via a simulation study.

Biomarkers↗

PubMed2002

Estimation of the area under the ROC curve.

The area under the receiver operating characteristic curve is frequently used as a measure for the effectiveness of diagnostic markers. In this paper we discuss and compare estimation procedures for this area. These are based on (i) the Mann-Whitney statistic; (ii) kernel smoothing; (iii) normal assumptions; (iv) empirical transformations to normality. These are compared in terms of bias and root mean square error in a large variety of situations by means of an extensive simulation study. Overall we find that transforming to normality usually is to be preferred except for bimodal cases where kernel methods can be effective.

Area Under Curve↗

PubMed2002

Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer.

BACKGROUND AND OBJECTIVES: Gemcitabine is an active agent in pancreatic cancer, with known radiosensitizing properties. Therefore, a phase II study was conducted to evaluate the efficacy of gemcitabine combined with radiation therapy in patients with localized unresectable adenocarcinoma of the pancreas. METHODS: Weekly gemcitabine at a dose of 1,000 mg/m(2) for 7 weeks was given as an induction phase. Patients who showed both clinical benefit response (CBR) and reduced or stable tumor size on computed tomography (CT) scan entered the chemoradiotherapy phase of the treatment. This consisted of gemcitabine 400 mg/m(2) weekly x3 every 28 days for 2 cycles, given concurrently with radiotherapy, for a total dose of 50.4 Gy in 28 fractions. After completion of radiotherapy, gemcitabine was continued as maintenance. RESULTS: Twenty patients entered this study. Ten patients (50%) achieved CBR to gemcitabine in the induction phase; these patients had no objective tumor progression and were therefore enrolled in the chemoradiotherapy phase. Four patients (20%) had a partial response, and three patients (15%) underwent pancreatectomy. Two patients had negative surgical margins, and in one patient histologic examination of the residual mass showed only fibrosis. The median survival for the entire group was 8 months, and the median survival has not yet been reached for the chemoradiotherapy group. CONCLUSIONS: Treatment with gemcitabine concomitant with radiation therapy according to the present schedule is well tolerated and can provide prolonged CBR and disease stabilization in patients with localized, unresectable pancreatic cancer.

Adenocarcinoma↗

PubMed2002

The association of hormone replacement therapy and coronary calcium as determined by electron beam tomography.

BACKGROUND: Observational studies have shown that hormone replacement therapy (HRT) is associated with lower coronary heart disease (CHD), and animal studies demonstrate potent antiatherosclerotic estrogen effects. Paradoxically, recent clinical trials have not demonstrated a protective effect. This paradox may be explained by a healthy woman effect bias. Women using HRT have improved health outcomes unrelated to underlying atherosclerotic burden. Examination of the association between coronary calcium (CC), a marker of atherosclerotic plaque burden, and the use of HRT in postmenopausal women may help address this paradox. METHODS: The study population comprised 641 asymptomatic postmenopausal women, 425 (66%) of whom were taking HRT. Data obtained from a self-administered questionnaire and blood samples were analyzed. Electron beam tomography (EBT) for CC was performed on each subject. Analysis of variance (ANOVA) was used to evaluate adjusted means. RESULTS: Independent t tests found that age, low-density lipoproteins (LDL), high-density lipoproteins (HDL), body mass index (BMI), vitamin use, coronary calcium score (CCS), coronary calcified volume (CCV), and the number of coronary calcium lesions (CCL) were significantly different between the HRT group and the non-HRT group. However, after controlling for potential confounders, no significant differences were observed in CCS, CCV, or the number of CCL between the HRT and non-HRT groups. Stratifying by BMI shows that obese/overweight women taking HRT have lower adjusted CCS and fewer CCL than the obese/overweight women not taking HRT. CONCLUSIONS: These findings demonstrate no association between HRT use and CCS, CCV, and CCL after adjusting for measurable confounders in postmenopausal women. Our failure to demonstrate an independent association between HRT use and a marker of atherosclerotic plaque burden suggests that a healthy woman effect may explain the beneficial association between HRT use and CHD in observational studies.

Aged↗