Chronic Disease Research Group

Minneapolis, MN, United States

Chronic Disease Research Group

Minneapolis, MN, United States
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Koopmeiners J.S.,University of Minnesota | Wey A.,Chronic Disease Research Group
Journal of Biopharmaceutical Statistics | Year: 2017

The primary object of a Phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose finding. Recently, it was shown that the CRM has a tendency to get “stuck” on a dose level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable tradeoff with respect to the average number treated at the MTD. © 2017 Taylor & Francis Group, LLC


Shroff G.R.,University of Minnesota | Li S.,Chronic Disease Research Group | Herzog C.A.,University of Minnesota
Journal of the American Society of Nephrology : JASN | Year: 2017

Analysis of a contemporary cohort of patients on dialysis revealed that mortality from acute myocardial infarction (AMI) has decreased, whereas the prevalence of AMI has increased markedly, particularly among patients with non-ST elevation myocardial infarction (NSTEMI). Using inpatient discharge diagnosis codes (1993-2008), we determined that proportions of AMI claims decreased in the primary position (from 65% to 52%) but increased in the secondary position (from 35% to 48%). Proportions of NSTEMI codes increased remarkably in both the primary and secondary positions. The progressive increase in diagnostic claims for secondary AMI identifies a unique high-risk population and has important clinical, economic, and epidemiologic implications among patients on dialysis. Copyright © 2017 by the American Society of Nephrology.


Shroff G.R.,University of Minnesota | Herzog C.A.,University of Minnesota | Herzog C.A.,Chronic Disease Research Group
Journal of the American Society of Nephrology | Year: 2016

Coronary revascularization decisions for patients with CKD stage 5D present a dilemma for clinicians because of high baseline risks of mortality and future cardiovascular events. This population differs from the general population regarding characteristics of coronary plaque composition and behavior, accuracy of noninvasive testing, and response to surgical and percutaneous revascularization, such that findings from the general population cannot be automatically extrapolated. However, this high-risk population has been excluded from all randomized trials evaluating outcomes of revascularization. Observational studies have attempted to address long-term outcomes after surgical versus percutaneous revascularization strategies, but inherent selection bias may limit accuracy. Compared with percutaneous strategies, surgical revascularization seems to have long-term survival benefit on the basis of observational data but associates with substantially higher short-term mortality rates. Percutaneous revascularization with drug-eluting and bare metal stents associates with a high risk of in-stent restenosis and need for future revascularization, perhaps contributing to the higher long-term mortality hazard. Off-pump coronary bypass surgery and the newest generation of drug-eluting stent platforms offer no definitive benefits. In this review, we address the nuances, complexities, and tradeoffs that clinicians face in determining the optimal method of coronary revascularization for this high-risk population. Copyright © 2016 by the American Society of Nephrology.


Obrador G.T.,Panamerican University of Mexico | Mahdavi-Mazdeh M.,Tehran University of Medical Sciences | Collins A.J.,Chronic Disease Research Group
American Journal of Kidney Diseases | Year: 2011

The Global Kidney Disease Prevention Network is an international public health organization devoted to encouraging and enhancing efforts to increase awareness and recognition of kidney disease, detect it early, and provide treatment to prevent disease progression, improve patient outcomes, and decrease costs. Twenty-six participants from 12 low-, middle-, and high-income countries attended the first meeting, held in Geneva, Switzerland, on September 12-13, 2009. Work groups discussed target populations for chronic kidney disease (CKD) screening, optimal parameters for screening on a public health level, evaluating the impact of early screening programs, and use of screening data to inform health care policy. Of the screening programs discussed, most have targeted populations at high risk of CKD and have included medical history; weight, height, and blood pressure measurements; and blood and urine tests. In screenees, CKD prevalence ranged from 11%-33%. In screenees with CKD, few were aware of the disease, although substantial proportions had been seen by a physician in the previous 6-12 months. At the policy level, prevention of CKD implies prevention and control of risk-factor conditions, including diabetes, hypertension, and others. Given the high prevalence and under-recognition of CKD in different countries, a concerted effort to globally improve primary and secondary CKD prevention appears to be warranted. © 2011 National Kidney Foundation, Inc.


Dharnidharka V.R.,University of Florida | Lamb K.E.,University of Florida | Lamb K.E.,Chronic Disease Research Group | Gregg J.A.,University of Florida | Meier-Kriesche H.-U.,University of Florida
American Journal of Transplantation | Year: 2012

In a prior multiorgan transplant database study, recipient Epstein - Barr virus (EBV) seronegativity was not associated with increased risk for posttransplant lymphoproliferative disorders (PTLD) in liver transplants (LTX), at variance with prior single center reports and with data from kidney and heart transplants (KTX and HTX). The Scientific Registry of Transplant Recipients (SRTR) in the United States is the only other registry with data on the required variables for comparison. Our study set comprised 112 756 KTX (580 PTLDs; 0.51%), 13 937 HTX (140 PTLDs; 1.0%) and 40 437 LTX (383 PTLDs; 0.95%) performed January 2003 onward. The unadjusted hazard ratio (HR) for PTLD if recipient EBV seronegative was 5.005 for KTX, 6.528 for HTX and 2.615 for LTX (p < 0.001 for all). In models adjusted for multiple covariates, the adjusted HR was 3.583 (p < 0.001) for KTX, 4.037 (p < 0.001) for HTX, 1.479 (p = 0.03) for LTX. Interaction models using EBV seropositive KTX as reference group showed significantly higher risk for all other EBV seronegative organ transplant groups and also for EBV seropositive LTX (AHR 2.053, p < 0.0001).Recipient EBV seronegativity is still significantly associated with risk for PTLD in LTX, though less so because of higher baseline risk in the EBV seropositive LTX group. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.


Majhail N.S.,Center for International Blood and Marrow Transplant Research | Mau L.W.,Chronic Disease Research Group | Denzen E.M.,National Marrow Donor Program | Arneson T.J.,Chronic Disease Research Group
Bone Marrow Transplantation | Year: 2013

There is a lack of multi-center cost-identification studies for hematopoietic cell transplantation (HCT). We used a single longitudinal administrative claims database representing a national, commercially insured population to evaluate the feasibility of identifying HCT recipients and to establish a cohort of autologous and allogeneic HCT recipients to study inpatient and outpatient direct medical costs from transplant hospitalization through first 100 days post-transplantation. Using ICD-9 procedure and diagnosis codes, we identified 3365 patients who had received their first transplant in the United States between 2007 and 2009 (autologous, 1678, allogeneic, 1320, graft source not specified, 367). The median 100-day total costs for autologous HCT were 99 899 (interquartile range (IQR), 73 914-140 555), and for allogeneic HCT were 203 026 (IQR, 141 742-316 426). The majority of costs (>75%) occurred during the initial transplant hospitalization for both autologous and allogeneic HCT recipients. Costs were greater among pediatric (≤20 years) compared with adult (>20 years) recipients and this difference was more pronounced with allogeneic HCT. Using a claims database representing a national HCT population, we highlight the high costs associated with autologous and allogeneic HCT. Our study lays the foundation for using claims data for future research on economic aspects of HCT. © 2013 Macmillan Publishers Limited All rights reserved.


Weinhandl E.D.,Chronic Disease Research Group | Liu J.,Chronic Disease Research Group | Gilbertson D.T.,Chronic Disease Research Group | Arneson T.J.,Chronic Disease Research Group | And 2 more authors.
Journal of the American Society of Nephrology | Year: 2012

Frequent hemodialysis improves cardiovascular surrogates and quality-of-life indicators, but its effect on survival remains unclear. We used a matched-cohort design to assess relative mortality in daily home hemodialysis and thrice-weekly in-center hemodialysis patients between 2005 and 2008. We matched 1873 home hemodialysis patients with 9365 in-center patients (i.e., 1:5 ratio) selected from the prevalent population in the US Renal Data System database. Matching variables included first date of follow-up, demographic characteristics, and measures of disease severity. The cumulative incidence of death was 19.2% and 21.7% in the home hemodialysis and in-center patients, respectively. In the intention-to-treat analysis, home hemodialysis associated with a 13% lower risk for all-cause mortality than in-center hemodialysis (hazard ratio [HR], 0.87; 95%confidence interval [95%CI], 0.78-0.97). Cause-specificmortality HRs were 0.92 (95% CI, 0.78-1.09) for cardiovascular disease, 1.13 (95% CI, 0.84-1.53) for infection, 0.63 (95% CI, 0.41-0.95) for cachexia/dialysis withdrawal, 1.06 (95%CI, 0.81-1.37) for other specified cause, and 0.59 (95% CI, 0.44-0.79) for unknown cause. Findings were similar using as-treated analyses. We did not detect statistically significant evidence of heterogeneity of treatment effects in subgroup analyses. In summary, these data suggest that relative to thrice-weekly in-center hemodialysis, daily home hemodialysis associates with modest improvements in survival. Continued surveillance should strengthen inference about causes of mortality and determine whether treatment effects are homogeneous throughout the dialysis population. Copyright © 2012 by the American Society of Nephrology.


Weinhandl E.D.,Chronic Disease Research Group | Arneson T.J.,Chronic Disease Research Group | St. Peter W.L.,Chronic Disease Research Group | St. Peter W.L.,University of Minnesota
American Journal of Kidney Diseases | Year: 2013

Background: Reducing medication-related problems and improving medication adherence in hemodialysis patients may improve clinical outcomes. In 2005, a large US dialysis organization created an integrated pharmacy program for its patients. We aimed to compare the outcomes of hemodialysis patients enrolled in this program and matched control patients. Study Design: Quality improvement report. Setting & Participants: Hemodialysis patients with concurrent Medicare and Medicaid eligibility who chose to receive program services and propensity score-matched controls; the propensity score was an estimated function of demographic characteristics, comorbid conditions, medication exposure, serum concentrations, and vascular access method. Quality Improvement Plan: Program services included medication delivery, refill management, medication list reviews, telephonic medication therapy management, and prior authorization assistance. Outcomes: Relative rates of death and hospitalization. Measurements: Survival estimates calculated with the Kaplan-Meier method; mortality hazards compared with Cox regression; hospitalization rates compared with Poisson regression. Results: In outcome models, there were 8,864 patients receiving integrated pharmacy services and 43,013 matched controls. In intention-to-treat and as-treated analyses, mortality HRs for patients receiving integrated pharmacy services versus matched controls were 0.92 (95% CI, 0.86-0.97) and 0.79 (95% CI, 0.74-0.84), respectively. Corresponding relative rates of hospital admissions were 0.98 (95% CI, 0.95-1.01) and 0.93 (95% CI, 0.90-0.96), respectively, and of hospital days, 0.94 (95% CI, 0.90-0.98) and 0.86 (95% CI, 0.82-0.90), respectively. Cumulative incidences of disenrollment from the pharmacy program were 23.4% at 12 months and 37.0% at 24 months. Limitations: Patients were not randomly assigned to receive integrated pharmacy services; as-treated analyses may be biased because of informative censoring by disenrollment from the pharmacy program; data regarding use of integrated pharmacy services were lacking. Conclusions: Receipt of integrated pharmacy services was associated with lower rates of death and hospitalization in hemodialysis patients with concurrent Medicare and Medicaid eligibility. Studies are needed to measure pharmacy program use and assess detailed clinical and economic outcomes. © 2013 National Kidney Foundation, Inc.


Liu J.,Chronic Disease Research Group | Foley R.N.,Chronic Disease Research Group
Kidney International | Year: 2012

Zhang et al. studied the relationship between day of the week and all-cause and cardiovascular mortality in the United States, Europe, and Japan. The study confirms findings of studies of US patients that risk of all-cause and cardiac mortality is higher after a long interdialytic interval, and shows that this is also true in Europe and Japan. Alternate-day dialysis may improve patient survival on hemodialysis, but randomized trials are necessary to establish a new schedule. © 2012 International Society of Nephrology.


Foley R.N.,Chronic Disease Research Group
Nature Reviews Nephrology | Year: 2010

The stimulation of erythropoiesis is a rapidly evolving area of research, with mechanistic insights often developing rapidly into therapeutic agents. A broad range of erythropoiesis-stimulating agents are currently in clinical use and many more under development are likely to enter the marketplace in the near future. To date, much of the investigative activity in this field has targeted activation of the erythropoietin receptor and factors that modulate hypoxia-related pathways of erythropoietin production within cells. This Review discusses newer erythropoiesis-stimulating agents currently under assessment for the treatment of anemia in patients with chronic kidney disease. Such agents include proteins and peptides that activate erythropoietin receptors, non-protein agents, and strategies with targets other than erythropoietin receptors. © 2010 Macmillan Publishers Limited. All rights reserved.

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