Statistical Evaluation of Continuous-Scale Diagnostic Tests with Missing Data

The receiver operating characteristic (ROC) curve methodology is the statistical methodology for assessment of the accuracy of diagnostics tests or bio-markers. Currently most widely used statistical methods for the inferences of ROC curves are complete-data based parametric, semi-parametric or nonparametric methods. However, these methods cannot be used in diagnostic applications with missing data. In practical situations, missing diagnostic data occur more commonly due to various reasons such as medical tests being too expensive, too time consuming or too invasive. This dissertation aims to develop new nonparametric statistical methods for evaluating the accuracy of diagnostic tests or biomarkers in the presence of missing data. Specifically, novel nonparametric statistical methods will be developed with different types of missing data for (i) the inference of the area under the ROC curve (AUC, which is a summary index for the diagnostic accuracy of the test) and (ii) the joint inference of the sensitivity and the specificity of a continuous-scale diagnostic test. In this dissertation, we will provide a general framework that combines the empirical likelihood and general estimation equations with nuisance parameters for the joint inferences of sensitivity and specificity with missing diagnostic data. The proposed methods will have sound theoretical properties. The theoretical development is challenging because the proposed profile log-empirical likelihood ratio statistics are not the standard sum of independent random variables. The new methods have the power of likelihood based approaches and jackknife method in ROC studies. Therefore, they are expected to be more robust, more accurate and less computationally intensive than existing methods in the evaluation of competing diagnostic tests

Validity and reliability of a short self-efficacy instrument for hypertension treatment adherence among adults with uncontrolled hypertension

Objective: To establish the reliability and validity of a self-report measure designed to assess self-efficacy for hypertension treatment adherence. Methods: This investigation was embedded within a six-month randomized clinical trial (RCT), which demonstrated that a tailored, stage-matched intervention was more effective at improving hypertension control than usual care among individuals (n = 533) with repeated uncontrolled hypertension. The instrument used to assess self-efficacy for hypertension treatment adherence (SE-HTA) comprised three subscales that assessed diet self-efficacy (DSE), exercise self-efficacy (ESE), and medication self-efficacy (MSE). To determine SE-HTA validity and reliability, we assessed internal consistency using Cronbach's α coefficients, conducted exploratory factor analysis, and evaluated convergent and discriminant validity, as well as test-retest reliability using Spearman's ρ correlation coefficients. Results: Cronbach's α (internal consistency) values for DSE, ESE, and MSE were 0.81, 0.82 and 0.74. Factor analysis and the scree plot demonstrated three distinct factors, which correspond to the three subscales contained in the SE-HTA instrument. SE-HTA possessed good convergent and discriminant validity, and moderate test-retest reliability. Conclusion: The SE-HTA instrument containing diet, exercise, and medication adherence subscales is valid and reliable in adults with uncontrolled hypertension. Practice implications: This SE-HTA instrument measures self-efficacy and could help facilitate behavior change in hypertension

Sustained Benefit of Alternate Behavioral Interventions to Improve Hypertension Control: A Randomized Clinical Trial

Little is known about the long-term effects of behavioral interventions to improve blood pressure (BP) control. We evaluated whether a telephone-delivered, behavioral stage-matched intervention (SMI), or a nontailored health education intervention (HEI) delivered for 6 months improves BP control (or lowers systolic BP) over 12 months, as well as its sustainability 6 months after intervention implementation ended, compared with usual care in participants with repeated uncontrolled BP at baseline. A 3-arm, randomized controlled trial was designed to evaluate the effectiveness of 2 interventions, each compared with a usual-care control group. Participants were 533 adults with persistent uncontrolled BP who were treated at 2 Veterans Affairs Medical Centers. The intervention was implemented for 6 months, followed by 6 months of observation. Compared with usual care, the odds of having BP under control over 12 months in SMI were 84% higher (odds ratio, 1.84 [95% CI, 1.28–2.67]; P=0.001), and 48% higher in HEI (odds ratio, 1.48 [95% CI, 1.02–2.14]; P=0.04).Over the 12 months, compared with usual care, systolic blood pressure was 2.80 mm Hg lower in SMI ([95% CI, 0.27 to 5.33]; P=0.03) while it was 2.58 mm Hg lower in HEI ([95% CI, −0.40 to 5.55]; P=0.09). From 6 to 12 months, SMI sustained improved BP control and lower systolic blood pressure, while HEI, which did not have significantly better BP control or lower systolic blood pressure at 6 months, appeared to improve BP control and lower systolic blood pressure. SMI and HEI are promising interventions that can be implemented in clinical practice to improve BP management

Access to diagnostic tests and essential medicines for cardiovascular diseases and diabetes care: cost, availability and affordability in the west region of Cameroon

Objective: To assess the availability and affordability of medicines and routine tests for cardiovascular disease (CVD) and diabetes in the West region of Cameroon, a low-income setting. METHODS: A survey was conducted on the availability and cost of twelve routine tests and twenty medicines for CVD and diabetes in eight health districts (four urban and four rural) covering over 60% of the population of the region (1.8 million). We analyzed the percentage of tests and medicines available, the median price against the international reference price (median price ratio) for the medicines, and affordability in terms of the number of days' wages it would cost the lowest-paid unskilled government worker for initial investigation tests and procurement for one month of treatment. RESULTS: The availability of tests varied between 10% for the ECG to 100% for the fasting blood sugar. The average cost for the initial investigation using the minimum tests cost 29.76 days' wages. The availability of medicines varied from 36.4% to 59.1% in urban and from 9.1% to 50% in rural settings. Only metformin and benzathine-benzylpenicilline had a median price ratio of ≤1.5, with statins being largely unaffordable (at least 30.51 days' wages). One month of combination treatment for coronary heart disease costs at least 40.87 days' wages. CONCLUSION: The investigation and management of patients with medium-to-high cardiovascular risk remains largely unavailable and unaffordable in this setting. An effective non-communicable disease program should lay emphasis on primary prevention, and improve affordable access to essential medicines in public outlets

Association between Arsenic Exposure from Drinking Water and Longitudinal Change in Blood Pressure among HEALS Cohort Participants

Background: Cross-sectional studies have shown associations between arsenic exposure and prevalence of high blood pressure; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking. Method: We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every 2 years after baseline. Mixed-effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with annual change in blood pressure during follow-up (median, 6.7 years). Result: In the HEALS population, the median water arsenic concentration at baseline was 62 μg/L. Individuals in the highest quartile of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in systolic blood pressure compared with those in the reference group (β = 0.48 mmHg/year; 95% CI: 0.35, 0.61, and β = 0.43 mmHg/year; 95% CI: 0.29, 0.56 for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models. Likewise, individuals in the highest quartile of baseline arsenic exposure had a greater annual increase in diastolic blood pressure for water arsenic and urinary creatinine-adjusted arsenic, (β = 0.39 mmHg/year; 95% CI: 0.30, 0.49, and β = 0.45 mmHg/year; 95% CI: 0.36, 0.55, respectively) compared with those in the lowest quartile. Conclusion: Our findings suggest that long-term arsenic exposure may accelerate age-related increases in blood pressure. These findings may help explain associations between arsenic exposure and cardiovascular disease

Variable Selection in ROC Regression

Regression models are introduced into the receiver operating characteristic (ROC) analysis to accommodate effects of covariates, such as genes. If many covariates are available, the variable selection issue arises. The traditional induced methodology separately models outcomes of diseased and nondiseased groups; thus, separate application of variable selections to two models will bring barriers in interpretation, due to differences in selected models. Furthermore, in the ROC regression, the accuracy of area under the curve (AUC) should be the focus instead of aiming at the consistency of model selection or the good prediction performance. In this paper, we obtain one single objective function with the group SCAD to select grouped variables, which adapts to popular criteria of model selection, and propose a two-stage framework to apply the focused information criterion (FIC). Some asymptotic properties of the proposed methods are derived. Simulation studies show that the grouped variable selection is superior to separate model selections. Furthermore, the FIC improves the accuracy of the estimated AUC compared with other criteria