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Browsing by Author "Wang, Chenkun"
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Item Antidepressant Use in the Elderly Is Associated With an Increased Risk of Dementia(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2016-04) Wang, Chenkun; Gao, Sujuan; Hendrie, Hugh C.; Kesterson, Joe; Campbell, Noll L.; Shekhar, Anantha; Callahan, Christopher M.; Biostatistics, School of Public HealthA retrospective cohort study was conducted including 3688 patients age 60 years or older without dementia enrolled in a depression screening study in primary care clinics. Information on antidepressant use and incident dementia during follow-up was retrieved from electronic medical records. The Cox proportional hazard models were used to compare the risk for incident dementia among 5 participant groups: selective serotonin re-uptake inhibitors (SSRI) only, non-SSRI only (non-SSRI), mixed group of SSRI and non-SSRI, not on antidepressants but depressed, and not on antidepressants and not depressed. SSRI and non-SSRI users had significantly higher dementia risk than the nondepressed nonusers (hazard ratio [HR]=1.83, P=0.0025 for SSRI users and HR=1.50, P=0.004 for non-SSRI users). In addition, SSRIs users had significantly higher dementia risk than non-users with severe depression (HR=2.26, P=0.0005). Future research is needed to confirm our results in other populations and to explore potential mechanism underlying the observed association.Item Comparison of matrix frequency-doubling technology perimetry and standard automated perimetry in monitoring the development of visual field defects for glaucoma suspect eyes(PLOS, 2017-05-18) Hu, Rongrong; Wang, Chenkun; Racette, Lyne; Ophthalmology, School of MedicineBACKGROUND: Perimetry is indispensable for the clinical management of glaucoma suspects. Our goal is to compare the performance of standard automated perimetry (SAP) and Matrix frequency-doubling technology (FDT) perimetry in monitoring the development of visual field (VF) defects in glaucoma suspect eyes. METHODS: Longitudinal data of paired SAP and FDT from 221 eyes of 155 glaucoma suspects enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. All eyes had glaucomatous optic neuropathy or ocular hypertension, but normal SAP and FDT results at baseline. The development of glaucomatous VF defects was defined as the presence of a cluster of ≥ 3 (less conservative) or ≥ 4 (more conservative) locations confirmed on ≥ 2 additional consecutive tests. Risk factors for the development of VF defects were analyzed by COX proportional hazard models. After conversion into common logarithmic units, the rates of change of global VF indices were fitted with linear mixed models. RESULTS: FDT detected more eyes that developed VF defects than SAP using the less conservative criterion, and no significant difference was observed using the more conservative criterion. For those eyes detected by both SAP and FDT, FDT detected the development of VF defects either earlier than SAP or simultaneously in most cases. Baseline structural measurements were not significantly associated with an increased risk for the development of glaucomatous VF defects on either SAP or FDT. Older age was significantly associated with the development of VF defects on FDT but not on SAP. Both SAP and FDT detected a progressing worsening trend of pattern standard deviation over time with a similar rate of change between these test types. CONCLUSIONS: Matrix FDT would be useful to monitor the onset of VF defects in glaucoma suspects and may outperform SAP in the early stage of glaucomatous VF damage.Item Flexible models of time-varying exposures(2015-05) Wang, Chenkun; Gao, Sujuan; Liu, Hai; Yu, Zhangsheng; Callahan, Christopher M.With the availability of electronic medical records, medication dispensing data offers an unprecedented opportunity for researchers to explore complex relationships among longterm medication use, disease progression and potential side-effects in large patient populations. However, these data also pose challenges to existing statistical models because both medication exposure status and its intensity vary over time. This dissertation focused on flexible models to investigate the association between time-varying exposures and different types of outcomes. First, a penalized functional regression model was developed to estimate the effect of time-varying exposures on multivariate longitudinal outcomes. Second, for survival outcomes, a regression spline based model was proposed in the Cox proportional hazards (PH) framework to compare disease risk among different types of time-varying exposures. Finally, a penalized spline based Cox PH model with functional interaction terms was developed to estimate interaction effect between multiple medication classes. Data from a primary care patient cohort are used to illustrate the proposed approaches in determining the association between antidepressant use and various outcomes.Item A penalized Cox proportional hazards model with multiple time-varying exposures(IMS, 2017) Wang, Chenkun; Liu, Hai; Gao, Sujuan; Biostatistics, School of Public HealthIn recent pharmacoepidemiology research, the increasing use of electronic medication dispensing data provides an unprecedented opportunity to examine various health outcomes associated with long-term medication usage. Often, patients may take multiple types of medications intended for the same medical condition and the medication exposure status and intensity may vary over time, posing challenges to the statistical modeling of such data. In this article, we propose a penalized Cox proportional hazards (PH) model with multiple functional covariates and potential interaction effects. We also consider constrained coefficient functions to ensure a diminishing medication effect over time. Hypothesis testing of interaction effect and main effect was discussed under the penalized Cox PH model setting. Our simulation studies demonstrate the adequate performance of the proposed methods for both parameter estimation and hypothesis testing. Application to a primary care depression cohort study was also illustrated to examine the effects of two common types of antidepressants on the risk of coronary artery disease.Item Redefined blood pressure variability measure and its association with mortality in elderly primary care patients(Ovid Technologies Wolters Kluwer -American Heart Association, 2014-07) Gao, Sujuan; Hendrie, Hugh C.; Wang, Chenkun; Stump, Timothy E.; Stewart, Jesse C.; Kesterson, Joe; Clark, Daniel O.; Callahan, Christopher M.; Department of Biostatistics, Richard M. Fairbanks School of Public HealthVisit-to-visit blood pressure (BP) variability has received considerable attention recently. The objective of our study is to define a variability measure that is independent of change over time and determine the association between longitudinal summary measures of BP measurements and mortality risk. Data for the study came from a prospective cohort of 2906 adults, aged ≥60 years, in an urban primary care system with ≤15 years of follow-up. Dates of death for deceased participants were retrieved from the National Death Index. Systolic and diastolic BP measurements from outpatient clinic visits were extracted from the Regenstrief Medical Record System. For each patient, the intercept, regression slope, and root mean square error for visit-to-visit variability were derived using linear regression models and used as independent variables in Cox proportional hazards models for both all-cause mortality and mortality attributable to coronary heart disease or stroke. Rate of change was associated with mortality risk in a U-shaped relationship and that participants with little or no change in BP had the lowest mortality risk. BP variability was not an independent predictor of mortality risk. By separating change over time from visit-to-visit variability in studies with relatively long follow-up, we demonstrated in this elderly primary care patient population that BP changes over time, not variability, were associated with greater mortality risk. Future research is needed to confirm our findings in other populations.