James S Kaufman

University of Colorado, Denver, CO, United States

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Publications (45)338.11 Total impact

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    ABSTRACT: Aims: The concentration of fibroblast growth factor 23 (FGF-23) is elevated in patients on dialysis. FGF receptors have been implicated in the pathogenesis of left ventricular (LV) hypertrophy. The objective of this study was to examine the associations between high plasma FGF-23 concentration and LV systolic dysfunction. Methods: We tested the hypothesis that high plasma FGF-23 concentration is associated with LV dysfunction in 110 chronic dialysis patients from the Homocysteine study who had paired echocardiograms performed for clinical indications. C-terminal FGF-23 concentrations were measured in stored plasma samples. Multivariate regression analyses were performed to evaluate the association of FGF-23 concentration with LV dysfunction. Results: Participants had a mean age of 60 ± 11 years. Median FGF-23 level and mean ejection fraction (EF) at baseline were 4,632 (1,384 - 14,997) RU/ml and 50 ± 13%, respectively. Median follow-up time was 1.9 years. Higher FGF-23 concentration was directly associated with decreases in EF during follow-up. After adjustment for demographics, baseline EF, hypertension, diabetes, cardiovascular disease, body mass index, systolic blood pressure, hemoglobin and markers of mineral metabolism, participants with FGF-23 in the highest tertile had an 8% decrease in EF compared to participants in the lowest tertile (β -8.0, 95% CI -15.5 to -0.53; p = 0.04). When FGF-23 was evaluated as a continuous variable, for every log10 increase in FGF-23, EF decreased during follow-up by 6.5% (β -6.5, 95% CI -11.3 to -1.73; p = 0.01). Conclusion: In conclusion, higher FGF-23 concentration is independently associated with LV systolic dysfunction in chronic dialysis patients.
    Clinical nephrology 07/2013; · 1.29 Impact Factor
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    ABSTRACT: Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial.
    Clinical Journal of the American Society of Nephrology 05/2013; · 5.07 Impact Factor
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    ABSTRACT: BACKGROUND: Northwestern Nicaragua has a high prevalence of chronic kidney disease (CKD) of unknown cause among young adult men. In addition, frequent occurrence of urinary tract infections (UTI) among men and a dysuria syndrome described by sugarcane workers as "chistata" are both reported. This study examines health professionals perceptions regarding etiology of these conditions and their treatment approaches, including use of potentially nephrotoxic medications. METHODS: Nineteen in-person semi-structured interviews were conducted in November 2010 among ten physicians and nine pharmacists practicing in the region. RESULTS: Health professionals perceived CKD as a serious and increasing problem in the region, primarily affecting young men working as manual laborers. All interviewees regarded occupational and environmental exposure to sun and heat, and dehydration as critical factors associated with the occurrence of CKD. These factors were also considered to play a role in the occurrence of chistata in the region. Health professionals indicated that reluctance among workers to hydrate might be influenced by perceptions of water contamination. Symptoms often were treated with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics and antibiotics. Physicians acknowledged that the diagnosis of UTI usually was not based on microbial culture and opined that the use of potentially nephrotoxic medications may be contributing to CKD. CONCLUSIONS: Interviews provided evidence suggesting that medications such as diuretics, antibiotics and NSAIDs are widely used and sold over the counter for symptoms that may be related to dehydration and volume depletion. These factors, alone or in combination, may be possible contributors to kidney damage. Acute kidney damage coupled with volume depletion and exposures including medications and infectious agents should be further evaluated as causal factors for CKD in this region.
    BMC Public Health 04/2013; 13(1):350. · 2.08 Impact Factor
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    ABSTRACT: Background: Fibroblast growth factor 23 (FGF23) has been associated with death in dialysis patients. Since FGF23 shares structural features with FGF19 subfamily members that exert hormonal control of fat mass, we hypothesized that high circulating FGF23 concentrations would be associated with the development of a uremic lipid profile and lower body mass index (BMI). Methods: This study was conducted among 654 patients receiving chronic hemodialysis. C-terminal FGF23 concentrations were measured in stored plasma samples. Linear regression was used to examine the cross-sectional associations of plasma FGF23 concentrations with BMI, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides. Cox proportional hazard models were used to examine the association between FGF23 concentrations and all-cause mortality. Results: Participants had a mean age of 60 ± 11 years and a median (IQR) FGF23 concentration of 4,212 (1,411-13,816) RU/ml. An increase per SD in log(10) FGF23 was associated with lower BMI (β = -1.11; p = 0.008), TC (β = -6.46; p = 0.02), LDL-C (β = -4.73; p = 0.04) and HDL-C (β = -2.14; p = 0.03); after adjusting for age, gender, race, cardiovascular risk factors, serum albumin, markers of mineral metabolism, and use of lipid-lowering drugs. The association of FGF23 with death was attenuated after adjustment for HDL-C (HR of highest quartile 1.53, 95% CI 1.06-2.20 compared to lowest quartile). Conclusion: These results indicate that higher plasma FGF23 levels are associated with lower BMI and dyslipidemia in dialysis patients. The association between FGF23 and death may be mediated through unexplored metabolic risk factors unrelated to mineral metabolism.
    American Journal of Nephrology 02/2013; 37(3):183-190. · 2.62 Impact Factor
  • James S Kaufman
    American Journal of Kidney Diseases 02/2013; 61(2):191-3. · 5.29 Impact Factor
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    ABSTRACT: Recent reports have described an apparent epidemic of CKD along the Pacific coast of Central America, such that CKD is a leading cause of death among working-age men in lower-altitude agricultural communities in this region. Given the limited availability of kidney replacement therapies in this region, CKD often is a terminal diagnosis, lending greater urgency to the identification of a modifiable cause. This article discusses the epidemiology of CKD in this region, reviews the clinical features of this CKD outbreak, discusses potential causes and the evidence supporting these hypotheses, and highlights the wider implications of this epidemic of CKD.
    Clinical Journal of the American Society of Nephrology 10/2012; · 5.07 Impact Factor
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    ABSTRACT: Background: Patients with chronic kidney disease (CKD) not requiring dialysis have a high prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency but the relationship between 25(OH)D levels and metabolic syndrome is unknown in this population. Methods: This study analyzed stored plasma samples from 495 non-diabetic subjects with severe kidney disease, not yet on dialysis, who participated in the homocysteine in kidney and end stage renal disease study. Metabolic syndrome was defined as the presence of all three of the following: (1) Serum triglycerides ≥ 150 mg/dl or drug treatment for hypertriglyceridemia; (2) serum high density lipoprotein-cholesterol (HDL-C) < 50 mg/dl for women or < 40 mg/dl for men or drug treatment for dyslipidemia; and (3) blood pressure ≥ 130/85 mmHg or drug treatment for hypertension. Multivariate logistic regression models were used to evaluate the cross-sectional association between plasma 25(OH)D levels and metabolic syndrome. Results: The prevalence of metabolic syndrome increased as 25(OH)D levels declined, with the highest prevalence in participants with 25(OH)D levels < 20 ng/ml. Participants with 25(OH)D levels < 20 ng/ml had a significantly increased risk of metabolic syndrome compared to subjects with levels > 30 ng/ml after adjustment for multiple confounders (OR 2.25, 95% CI 1.25 - 4.07). Plasma 25(OH)D levels were inversely associated with diastolic blood pressure (R = -0.10, p = 0.029) and serum triglyceride levels (R = -0.14, p = 0.002). Conclusion: 25(OH)D deficiency is strongly associated with an increased risk of metabolic syndrome in non-diabetic patients with severe CKD not yet on dialysis, independent of cardiometabolic risk factors and other important regulators of mineral metabolism.
    Clinical nephrology 07/2012; · 1.29 Impact Factor
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    ABSTRACT: Low vitamin D concentrations are prevalent in patients with chronic kidney disease (CKD). We investigated the relationship between plasma 25-hydroxyvitamin D (25[OH]D) or 1,25-dihydroxyvitamin D (1,25[OH](2)D) concentrations with death, cardiovascular events, and dialysis therapy initiation in patients with advanced CKD. The HOST (Homocysteinemia in Kidney and End Stage Renal Disease) Study was a randomized double-blind trial evaluating the effects of high doses of folic acid on death and long-term dialysis therapy initiation in patients with advanced CKD (stages 4 and 5 not yet on dialysis therapy). 25(OH)D and 1,25(OH)(2)D were measured in stored plasma samples obtained 3 months after trial initiation and evaluated at clinically defined cutoffs (<10, 10-30, and >30 ng/mL) and tertiles (<15, 15-22, and >22 pg/mL), respectively. Cox proportional hazard models were used to examine the association between vitamin D concentrations and clinical outcomes. 1,099 patients with advanced CKD from 36 Veteran Affairs Medical Centers. 25(OH)D and 1,25(OH)(2)D concentrations. Death, cardiovascular events, and time to initiation of long-term dialysis therapy. After a median follow-up of 2.9 years, 41% (n = 453) died, whereas 56% (n = 615) initiated dialysis therapy. Mean 25(OH)D and 1,25(OH)(2)D concentrations were 21 ± 10 ng/mL and 20 ± 11 pg/mL, respectively. After adjustment for potential confounders, the lowest tertile of 1,25(OH)(2)D was associated with death (HR, 1.33; 95% CI, 1.01-1.74) and initiation of long-term dialysis therapy (HR, 1.78; 95% CI, 1.40-2.26) compared with the highest tertile. The association with death and initiation of dialysis therapy was moderately attenuated after adjustment for plasma fibroblast growth factor 23 (FGF-23) concentrations (HRs of lower tertiles of 1.20 [95% CI, 0.91-1.58] and 1.56 [95% CI, 1.23-1.99], respectively, compared with highest tertile). There was no association between 25(OH)D concentrations and outcomes. Participants were mostly men. Low plasma 1,25(OH)(2)D concentrations are associated with death and initiation of long-term dialysis therapy in patients with advanced CKD. FGF-23 level may attentuate this relationship.
    American Journal of Kidney Diseases 05/2012; 60(4):567-75. · 5.29 Impact Factor
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    ABSTRACT: AKI remains an important clinical problem, with a high mortality rate, increasing incidence, and no Food and Drug Administration-approved therapeutics. Advances in addressing this clinical need require approaches for rapid diagnosis and stratification of injury, development of therapeutic agents based on precise understanding of key pathophysiological events, and implementation of well designed clinical trials. In the near future, AKI biomarkers may facilitate trial design. To address these issues, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a meeting, "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers," in December of 2010 that brought together academic investigators, industry partners, and representatives from the National Institutes of Health and the Food and Drug Administration. Important issues in the design of clinical trials for interventions in AKI in patients with sepsis or AKI in the setting of critical illness after surgery or trauma were discussed. The sepsis working group discussed use of severity of illness scores and focus on patients with specific etiologies to enhance homogeneity of trial participants. The group also discussed endpoints congruent with those endpoints used in critical care studies. The second workgroup emphasized difficulties in obtaining consent before admission and collaboration among interdisciplinary healthcare groups. Despite the difficult trial design issues, these clinical situations represent a clinical opportunity because of the high event rates, severity of AKI, and poor outcomes. The groups considered trial design issues and discussed advantages and disadvantages of several short- and long-term primary endpoints in these patients.
    Clinical Journal of the American Society of Nephrology 03/2012; 7(5):856-60. · 5.07 Impact Factor
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    ABSTRACT: Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.
    Clinical Journal of the American Society of Nephrology 03/2012; 7(5):844-50. · 5.07 Impact Factor
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    ABSTRACT: AKI is an important clinical problem that has become increasingly more common. Mortality rates associated with AKI remain high despite advances in supportive care. Patients surviving AKI have increased long-term mortality and appear to be at increased risk of developing CKD and progressing to ESRD. No proven effective pharmacologic therapies are currently available for the prevention or treatment of AKI. Advances in addressing this unmet need will require the development of novel therapeutic agents based on precise understanding of key pathophysiological events and the implementation of well designed clinical trials. To address this need, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored the "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" workshop in December 2010. The event brought together representatives from academia, industry, the National Institutes of Health, and the US Food and Drug Administration. We report the discussions of workgroups that developed outlines of clinical trials for the prevention of AKI in two patient populations: patients undergoing elective surgery who are at risk for or who develop AKI, and patients who are at risk for contrast-induced AKI. In both of these populations, primary prevention or secondary therapy can be delivered at an optimal time relative to kidney injury. The workgroups detailed primary and secondary endpoints for studies in these groups, and explored the use of adaptive clinical trial designs for trials of novel preventive strategies to improve outcomes of patients with AKI.
    Clinical Journal of the American Society of Nephrology 03/2012; 7(5):851-5. · 5.07 Impact Factor
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    ABSTRACT: This study examined differences in the concentration of markers of mineral metabolism across race in patients with advanced CKD not requiring dialysis and ESRD. Concentrations of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), intact parathyroid hormone (iPTH), and fibroblast growth factor 23 (FGF-23) were measured in stored plasma samples of 1497 patients with advanced CKD not yet on dialysis and ESRD who participated in the Homocysteine in Kidney and End Stage Renal Disease study. Linear regression models were used to examine the relationship between race and 25(OH)D, 1,25(OH)(2)D, iPTH, and FGF-23 concentrations. Non-Hispanic white patients comprised 58% of the cohort, whereas non-Hispanic blacks comprised 42%. Median (interquartile range) FGF-23 concentrations were lower in blacks compared with whites with CKD (323 [181-655] versus 431 [232-1026] RU/ml; P<0.001) but not in ESRD. In adjusted linear regression models, blacks with CKD not requiring dialysis had significantly lower plasma FGF-23 concentrations (difference, -159; 95% confidence interval, -205 to -106; P<0.001) compared with whites, independent of plasma 25(OH)D, 1,25(OH)(2)D, and iPTH concentrations. This difference was not observed in the ESRD group. The magnitude of correlation for the relationships between 1,25(OH)(2)D with iPTH, FGF-23 with 1,25(OH)(2)D, and FGF-23 with iPTH were stronger among blacks than whites with CKD not requiring dialysis. In advanced CKD not requiring dialysis, blacks have lower FGF-23 concentrations than whites. Blacks with CKD and ESRD have lower 25(OH)D and higher iPTH compared with whites, independent of FGF-23 concentrations.
    Clinical Journal of the American Society of Nephrology 03/2012; 7(4):640-7. · 5.07 Impact Factor
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    ABSTRACT: Healthcare for end-stage renal disease (ESRD) is intensive, expensive, and provided in both the public and private sector. Using a societal perspective, we examined healthcare costs and health outcomes for Department of Veterans Affairs (VA) ESRD patients comparing those who received hemodialysis care at VA versus private sector facilities. Dialysis patients were recruited from 8 VA medical centers from 2001 through 2003 and followed for 12 months in a prospective cohort study. Patient demographics, clinical characteristics, quality of life, healthcare use, and cost data were collected. Healthcare data included utilization (VA), claims (Medicare), and patient self-report. Costs included VA calculated costs, Medicare dialysis facility reports and reimbursement rates, and patient self-report. Multivariable regression was used to compare costs between patients receiving dialysis at VA versus private sector facilities. The cohort comprised 334 patients: 170 patients in the VA dialysis group and 164 patients in the private sector group. The VA dialysis group had more comorbidities at baseline, outpatient and emergency visits, prescriptions, and longer hospital stays; they also had more conservative anemia management and lower baseline urea reduction ratio (67% vs. 72%; P<0.001), although levels were consistent with guidelines (Kt/V≥1.2). In adjusted analysis, the VA dialysis group had $36,431 higher costs than those in the private sector dialysis group (P<0.001). Continued research addressing costs and effectiveness of care across public and private sector settings is critical in informing health policy options for patients with complex chronic illnesses such as ESRD.
    Medical care 09/2011; 50(2):161-70. · 3.24 Impact Factor
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    ABSTRACT: Concentrations of the phosphate-regulating hormone fibroblast growth factor-23 (FGF-23) are elevated in patients with chronic kidney disease (CKD), but whether higher plasma FGF-23 concentrations associate with all-cause mortality, cardiovascular events, or initiation of chronic dialysis is not completely understood. Here, we measured FGF-23 concentration in stored plasma samples from 1099 patients with advanced CKD who participated in The Homocysteine in Kidney and End Stage Renal Disease study. Mean serum phosphorus concentration was 4.3 mg/dl, median FGF-23 concentration was 392 RU/ml, and mean GFR was 18 ml/min/1.73 m(2). During a median follow-up of 2.9 yr, 453 (41%) patients died from any cause, 215 (20%) had a cardiovascular event, and 615 (56%) initiated chronic dialysis. Compared with the lowest quartile of FGF-23, each subsequent quartile associated with a progressively higher risk for death, adjusted for confounders (HR [95% CI] of 1.24 [0.91 to 1.69], 1.76 [1.28 to 2.44], and 2.17 [1.56 to 3.08] for the second through fourth quartiles, respectively). In addition, compared with the lowest quartile, the two highest quartiles of FGF-23 also associated with a significantly elevated risk for cardiovascular events and initiation of chronic dialysis. In conclusion, in advanced CKD, FGF-23 strongly and independently associates with all-cause mortality, cardiovascular events, and initiation of chronic dialysis.
    Journal of the American Society of Nephrology 09/2011; 22(10):1913-22. · 8.99 Impact Factor
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    ABSTRACT: BACKGROUND: Assessment of adherence to study medications is a common challenge in clinical research. Counting unused study medication is the predominant method by which adherence is assessed in outpatient clinical trials but it has limitations that include questionable validity and burdens on research personnel. PURPOSE: To compare capsule counts, patient questionnaire responses, and plasma drug levels as methods of determining adherence in a clinical trial that had 2056 participants and used centralized drug distribution and patient follow-up. METHODS: Capsule counts from study medication bottles returned by participants and responses to questions regarding adherence during quarterly telephone interviews were averaged and compared. Both measures were compared to plasma drug levels obtained at the 3-month study visit of patients in the treatment group. Counts and questionnaire responses were converted to adherence rates (doses taken divided by days elapsed) and were categorized by stringent (≥85.7%) and liberal (≥71.4%) definitions. We calculated the prevalence-adjusted bias-adjusted kappa to assess agreement between the two measures. RESULTS: Using a pre-paid mailer, participants returned 76.0% of study medication bottles to the central pharmacy. Both capsule counts and questionnaire responses were available for 65.8% of participants and were used to assess adherence. Capsule counts identified more patients who were under-adherent (18.8% by the stringent definition and 7.5% by the liberal definition) than self-reports did (10.4% by the stringent definition and 2.1% by the liberal definition). The prevalence-adjusted bias-adjusted kappa was 0.58 (stringent) and 0.83 (liberal), indicating fair and very good agreement, respectively. Both measures were also in agreement with plasma drug levels determined at the 3-month visit (capsule counts: p = 0.005 for the stringent and p = 0.003 for the liberal definition; questionnaire: p = 0.002 for both adherence definitions). LIMITATIONS: Inconsistent bottle returns and incomplete notations of medication start and stop dates resulted in missing data but exploratory missing data analyses showed no reason to believe that the missing data resulted in systematic bias. CONCLUSIONS: Depending upon the definition of adherence, there was fair to very good agreement between questionnaire results and capsule counts among returned study bottles, confirmed by plasma drug levels. We conclude that a self-report of medication adherence is potentially comparable to capsule counts as a method of assessing adherence in a clinical trial, if a relatively low adherence threshold is acceptable, but adherence should be confirmed by other measures if a high adherence threshold is required.
    Clinical Trials 08/2011; · 2.20 Impact Factor
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    ABSTRACT: Access to nephrology care before initiation of chronic dialysis is associated with improved outcomes after initiation. Less is known about the effect of predialysis nephrology care on healthcare costs and utilization. We conducted retrospective analyses of elderly patients who initiated dialysis between January 1, 2000 and December 31, 2001 and were eligible for services covered by the Department of Veterans Affairs. We used multivariable generalized linear models to compare healthcare costs for patients who received no predialysis nephrology care during the year before dialysis initiation with those who received low- (1-3 nephrology visits), moderate- (4-6 visits), and high-intensity (>6 visits) nephrology care during this time period. There were 8022 patients meeting inclusion criteria: 37% received no predialysis nephrology care, while 24% received low, 16% moderate, and 23% high-intensity predialysis nephrology care. During the year after dialysis initiation, patients in these groups spent an average of 52, 40, 31, and 27 days in the hospital (P < 0.001), respectively, and accounted for an average of $103,772, $96,390, $93,336, and $89,961 in total healthcare costs (P < 0.001), respectively. Greater intensity of predialysis nephrology care was associated with lower costs even among patients whose first predialysis nephrology visit was ≤ 3 months before dialysis initiation. Patients with greater predialysis nephrology care also had lower mortality rates during the year after dialysis initiation (43%, 38%, 28%, and 25%, respectively, P < 0.001). Greater intensity of predialysis nephrology care was associated with fewer hospital days and lower total healthcare costs during the year after dialysis initiation, even though patients survived longer.
    Medical care 03/2011; 49(3):248-56. · 3.24 Impact Factor
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    ABSTRACT: Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care. We describe a novel randomized clinical trial that uses the informatics and statistics infrastructure of the Veterans Affairs Healthcare System (VA) to illustrate one key component (called the point-of-care clinical trial - POC-CT) of a 'learning healthcare system,' and settles a clinical question of interest to the VA. This study is an open-label, randomized trial comparing sliding scale regular insulin to a weight-based regimen for control of hyperglycemia, using the primary outcome length of stay, in non-ICU inpatients within the northeast region of the VA. All non-ICU patients who require in-hospital insulin therapy are eligible for the trial, and the VA's automated systems will be used to assess eligibility and present the possibility of randomization to the clinician at the point of care. Clinicians will indicate their approval for informed consent to be obtained by study staff. Adaptive randomization will assign up to 3000 patients, preferentially to the currently 'winning' strategy, and all care will proceed according to usual practices. Based on a Bayesian stopping rule, the study has acceptable frequentist operating characteristics (Type I error 6%, power 86%) against a 12% reduction of median length of stay from 5 to 4.4 days. The adaptive stopping rule promotes implementation of a successful treatment strategy. Despite clinical equipoise, individual healthcare providers may have strong treatment preferences that jeopardize the success and implementation of the trial design, leading to low rates of randomization. Unblinded treatment assignment may bias results. In addition, generalization of clinical results to other healthcare systems may be limited by differences in patient population. Generalizability of the POC-CT method depends on the level of informatics and statistics infrastructure available to a healthcare system. The methods proposed will demonstrate outcome-based evaluation of control of hyperglycemia in hospitalized veterans. By institutionalizing a process of statistically sound and efficient learning, and by integrating that learning with automatic implementation of best practice, the participating VA Healthcare Systems will accelerate improvements in the effectiveness of care.
    Clinical Trials 01/2011; 8(2):183-95. · 2.20 Impact Factor
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    Ann M O'Hare, Michael Allon, James S Kaufman
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    ABSTRACT: Patients who initiate chronic dialysis with a functional arteriovenous (AV) fistula survive longer and experience fewer complications after initiation of dialysis than those who require a catheter. However, more than 80% of patients in this country begin chronic dialysis with a catheter rather than a fistula, either because they do not have a permanent access or their permanent access is not ready for use. Increasing rates of predialysis AV fistula placement is thus considered a priority area for predialysis care in this country. However, achievement of a functional AV fistula by the time of dialysis initiation is not always an easy proposition. We here outline the limitations of currently recommended approaches toward timing of AV fistula placement. We also highlight the potential complexity of patient and clinician decision making in this area. Particularly in the presence of advanced age and a high burden of comorbidity and disability, it is often uncertain whether patients will need, want, or benefit from chronic dialysis. Adding to this uncertainty, it is often not known whether, when, and after how many revisions an AV fistula will be sufficiently mature to support dialysis. We argue that it is important to acknowledge the complexity of medical decision making in this area and the limitations of currently available prognostic tools to guide such decision making. We conclude that initiation of dialysis with a catheter is appropriate for patients in whom the perceived harms of preemptive fistula placement outweigh the expected benefit.
    Seminars in Dialysis 09/2010; 23(5):452-5. · 2.25 Impact Factor
  • Nephrology news & issues 06/2010; 24(7):30, 32, 34.
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    ABSTRACT: People are exposed to various potentially toxic agents and conditions in their natural and occupational environments. These agents may be physical or chemical, may enter the human body through oral, inhalational, or transdermal routes, and may exert effects on all organ systems. Several well-known as well as lesser known associations exist between chronic kidney disease (CKD) and both environmental agents and conditions, such as heavy metals, industrial chemicals, elevated ambient temperatures, and infections. The effects of these agents may be modulated by genetic susceptibility and other comorbid conditions and may lead to the development of acute and CKD. In this article, we present environmental factors that are associated with CKD.
    Advances in chronic kidney disease 05/2010; 17(3):254-64. · 2.42 Impact Factor

Publication Stats

1k Citations
131 Downloads
3k Views
338.11 Total Impact Points

Institutions

  • 2012–2013
    • University of Colorado
      • Division of Renal Diseases and Hypertension
      Denver, CO, United States
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, IN, United States
  • 2001–2013
    • U.S. Department of Veterans Affairs
      • Center for Management of Complex Chronic Care (CMC3)
      Washington, Washington, D.C., United States
  • 2010
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2004–2010
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2002–2010
    • Boston University
      • • Renal Section
      • • Department of Medicine
      Boston, MA, United States
  • 2005–2009
    • University of Iowa
      • Division of Nephrology
      Iowa City, Iowa, United States
  • 2000
    • Richard L. Roudebush VA Medical Center
      Indianapolis, Indiana, United States