End stage renal disease is associated with accelerated mortality, and cardiovascular (CV) disease is the leading cause of death. Of relevance to more effective care of patients on dialysis is characterizing how outcome trajectories evolve over time and identifying their associated risk factors. Elucidating the time-varying effects of patient-level risk factors, such as infection, and facility-level characteristic, such as facilities' patient care staffing composition, on patients' CV outcome over time, from the start of dialysis is important. Our long-term goal is to provide guidance in identifying modifiable patient-level and facility-level risk factors and approaches to quality improvement of dialysis care providers. Towards this goal, we will develop a general framework to estimation and inference for multilevel time-dynamic modeling of patient outcomes that accommodates multilevel data structures (e.g., patients nested within dialysis facilities or care providers and observations over time nested within patients). Our proposed novel modeling of time- dynamic effects of risk factors of CV events and infection in patients on dialysis, is important for designing effective approaches to disease management and prevention because it allows identification of specific time periods of increased risk. In addition, the proposed framework is o relevant to facility-level decision making, including prediction of whether changes in a dialysis facility's patient care strategy would lead to improved patient outcome over time, as well as time-dynamic performance evaluation. Innovation. To date, there does not exist a feasible framework for estimation and dual inference (patient- and facility-level) in multilevel varying coefficient modeling (MVCM) that accommodates multilevel longitudinal data structures. Our work will be the first to study both patient- and facility-level inference in MVCM simultaneously and to flexibly model facility-level effects that span a spectrum of models, including facility (i) fixed effects, (ii) constant random effects, and (iii) random effects functions of time (random coefficient functions). This will also be the first study to examine continuous dialysis facility performance assessment from initiation of dialysis and allow for identification of specific time periods for targeted patient outcome improvement.
Aims. The proposed framework will be achieved through the following specific aims: 1) (Subject-level Inference) To develop and apply MVCM for multilevel longitudinal response (outcome) with general subject- level covariates and flexible modeling of facility-level effects; 2) (Facility-level Inference) To develop and apply MVCM for facility-level inference; 3) (MVCM Performance Characteristics) To characterize the operational characteristics of MVCM, including relative efficiency and sensitivity to modeling assumptions, across information sparsity levels and inferential goals.

Public Health Relevance

Understanding time-dynamic effects of risk factors on outcomes of patients with chronic diseases, such as cardiovascular events and infections in patients on dialysis, is important for effective disease management and prevention. The application involves developing new methods for multilevel time- dynamic modeling of patient outcomes using the United States Renal Data System. The goal is to provide guidance in identifying modifiable patient-level and facility-level risk factors and approaches to quality improvement of dialysis care providers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK092232-07
Application #
9618868
Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Abbott, Kevin C
Project Start
2011-09-15
Project End
2020-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Estes, Jason P; Nguyen, Danh V; Chen, Yanjun et al. (2018) Time-dynamic profiling with application to hospital readmission among patients on dialysis. Biometrics :
Li, Yihao; Nguyen, Danh V; Chen, Yanjun et al. (2018) Modeling time-varying effects of multilevel risk factors of hospitalizations in patients on dialysis. Stat Med 37:4707-4720
Estes, Jason P; Nguyen, Danh V; Chen, Yanjun et al. (2018) Rejoinder: Time-dynamic profiling with application to hospital readmission among patients on dialysis. Biometrics :
Chou, Jason A; Streja, Elani; Nguyen, Danh V et al. (2018) Intradialytic hypotension, blood pressure changes and mortality risk in incident hemodialysis patients. Nephrol Dial Transplant 33:149-159
Rhee, Connie M; Kalantar-Zadeh, Kamyar; Ravel, Vanessa et al. (2018) Thyroid Status and Death Risk in US Veterans With Chronic Kidney Disease. Mayo Clin Proc 93:573-585
Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P; Streja, Elani et al. (2017) Transition of care from pre-dialysis prelude to renal replacement therapy: the blueprints of emerging research in advanced chronic kidney disease. Nephrol Dial Transplant 32:ii91-ii98
You, Amy S; Kalantar-Zadeh, Kamyar; Lerner, Lorena et al. (2017) Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort. Cardiorenal Med 7:158-168
Campos, Luis Fernando; ?entürk, Damla; Chen, Yanjun et al. (2017) Bias and estimation under misspecification of the risk period in self-controlled case series studies. Stat (Int Stat Inst) 6:373-389
Rhee, Connie M; You, Amy S; Nguyen, Danh V et al. (2017) Thyroid Status and Mortality in a Prospective Hemodialysis Cohort. J Clin Endocrinol Metab 102:1568-1577
Rhee, Connie M; Kovesdy, Csaba P; Ravel, Vanessa A et al. (2017) Association of Glycemic Status During Progression of Chronic Kidney Disease With Early Dialysis Mortality in Patients With Diabetes. Diabetes Care 40:1050-1057

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