Survival analysis using Medicare data: example and methods.

OBJECTIVE: To describe key methods and issues in conducting survival analyses, especially using Medicare (and other) administrative data. PRINCIPAL FINDINGS: Survival analyses are rich , informative, and underutilized methods for examining out comes whose timing is important . Medicare files contain the necessary information for conducting such analyses, including identification of cohorts, definition of events, censoring of observations, and adjustment for covariates. CONCLUSION: Survival analyses can readily be conducted using the information contained in administrative data files.

How much better can we predict dialysis patient survival using clinical data?

OBJECTIVE: To use three approaches to compare dialysis survival prediction based on variables included in the Standardized Mortality Ratio (SMR) with prediction based on a clinically enriched set of variables. DATA SOURCE: The United States Renal Data System Case Mix Severity data set containing demographic, clinical, functional, nutritional, and treatment details about a random sample of 4,797 adult dialysis patients from 291 treatment units, incident to dialysis in 1986 and 1987. STUDY DESIGN: This observational study uses baseline patient characteristics in two proportional hazards survival models: the BASE model incorporates age, race, sex, and cause of end-stage renal disease (ESRD); the FULL model includes these and additional clinical information. We compare each model's performance using (1) the c-index, (2) observed median survival in strata of predicted risk, and (3) predicted survival for patients with different characteristics. PRINCIPAL FINDINGS: The FULL model's c-index (0.709, 0.708-0.711) is significantly higher than that of the BASE model (0.675, 0.675-0.676), indicating better discrimination. Second, the sickest patients identified by the FULL model were in fact sicker than those identified as sickest by the BASE model, with observed median survival of 451 days versus 524. Third, survival predictions for sickest patients using the FULL model are one-third shorter than those based on the BASE model. CONCLUSIONS: The model with more detailed clinical information predicted survival better than the BASE model. Clinical characteristics enable more accurate predictions, particularly for the sickest patients. Thus, clinical characteristics should be considered when making quality assessments for dialysis patients.

Does the survival advantage of nonwhite dialysis patients persist after case mix adjustment?

PURPOSE: Nonwhite dialysis patients survive longer than white patients; however, their clinical characteristics differ. We examined whether case mix differences explain the apparent survival advantage of nonwhite dialysis patients. SUBJECTS AND METHODS: We performed a prospective cohort study using data from the US Renal Data System Case Mix Severity Study that included 4,797 randomly selected dialysis patients 20 years of age and older who were followed up for up to 6 years. Demographic, comorbidity, laboratory, nutritional, and functional status data were obtained. Multivariable proportional hazards models adjusted for case mix differences between nonwhite and white dialysis patients. Additional analyses examined the effects of differences in transplantation rates, withdrawal from dialysis rates, and treatment modality selection. RESULTS: Unadjusted survival rates of black, Native American, and Asian or Pacific Islander dialysis patients were similar, and better than that for white dialysis patients. Relative to whites, the unadjusted relative risk (RR) for mortality among nonwhite patients was 0.64 (95% confidence interval [CI]: 0.58 to 0.70). Adjustment for case mix reduced, but did not eliminate, the survival advantage associated with nonwhite race (RR = 0.78, CI: 0.71 to 0.86). Adjustment for differences in transplantation rates (RR = 0.83, CI: 0.75 to 0.91), withdrawal from dialysis rates (RR = 0.81, CI: 0.73 to 0.90), and initial treatment modality (RR = 0.79, CI: 0.71 to 0.87) did not explain the lower mortality among nonwhites. CONCLUSIONS: A survival advantage for nonwhite dialysis patients persists after case mix adjustment. Future studies should explore additional physiologic and socioeconomic factors that might explain this difference.

Primary hyperaldosteronism causing posttransplantation hypertension: localization by adrenal vein sampling.

A 58 year-old man with end-stage renal disease who had received a cadaveric renal transplant presented with persistent hypertension and hypokalemia. Allograft renal artery stenosis, rejection, and cyclosporine effects were excluded. Hypokalemia persisted despite potassium supplementation and antihypertensive medications with hyperkalemic effects. The biochemical findings of primary hyperaldosteronism with a normal adrenal anatomy imaged by magnetic resonance imaging (MRI) necessitated adrenal vein sampling to lateralize a left adrenal adenoma. His hypokalemia was cured by the removal of the adenoma, and his blood pressure (BP) control was easily achieved with a less complex regimen of antihypertensives. We suggest that the concomitant existence of resistant hypokalemia and posttransplantation hypertension, especially in the cyclosporine era, should stimulate a search for hyperaldosteronism; once transplant renal artery stenosis has been excluded, the patient should be investigated for primary hyperaldosteronism. When imaging studies fail to show adrenal pathology, adrenal vein sampling will likely do so.

Magnetic resonance angiography in the evaluation of living-related renal donors.

Live-donor kidney donation requires an accurate determination of renal arterial anatomy. Traditionally, conventional angiography has supplied this information. The present study was undertaken to determine the accuracy of magnetic resonance angiography (MRA) compared with conventional angiography (CA) in the evaluation of potential living renal donors. Fifteen potential living renal donors underwent both conventional angiography (midstream aortic injection) and three-dimensional phase contrast MRA. Two overlapping volumes of 64 slices (slice thickness 1.5 mm) were obtained in the axial plane to allow coverage from the celiac trunk to the aortic bifurcation. Conventional angiography demonstrated single renal arteries in 24 kidneys and multiple renal arteries in 6 kidneys. Magnetic resonance angiography demonstrated multiple renal arteries in 5 of the 6 kidneys. The sensitivity of MRA in determining kidneys with multiple renal arteries was 83% (5/6). One kidney with an accessory 2-mm polar artery was incorrectly identified as having a single renal artery by MRA. The overall accuracy of MRA in identifying the number of renal arteries was 97% (29/30). Fibromuscular dysplasia was demonstrated in 2 patients by CA, but was not visualized prospectively by MRA. Based on standard physician and hospital fees for each procedure, use of MRA alone would represent a cost savings of approximately $1900 over CA. Despite its minimally invasive and economic attractions, MRA does not achieve the level of accuracy required to replace CA in the evaluation of potential living kidney donors.

Measuring, managing, and improving the quality of end-stage renal disease care.

As the federal end-stage renal disease (ESRD) program enters its third decade, it continues to grow both in terms of patient enrollment and cost. High visibility as well as patient, physician, and societal concerns regarding ESRD treatment outcomes and expenditures make the development of improved and expanded quality assurance and improvement (QA/QI) mechanisms for the ESRD program vital. The purpose of a QA/QI program is to identify and apply techniques for assessing and improving ESRD care quality to achieve the best possible outcome for all patients who can benefit medically, within the expenditure constraints set by society. Current QA knowledge and methods are reviewed in this article and are judged to be useful but of limited value. Limitations of current quality assessment tools, provider resistance, and inadequate governmental support are substantial barriers to implementation of a QA program. An ESRD QA/QI program should develop improved QA tools at the same time that available tools are cautiously put to work. Such a program would be based in individual treatment units, using existing network and US Renal Data System structures and a new national ESRD QA committee for support and oversight. As additional ESRD QA data become available, providers would incorporate the new information into decision making at all levels to enhance patient outcome. Substantial financial support from the government will be needed to implement such a quality program. A comprehensive ESRD QA program could serve as a model for QA for the national health care system.

1,25-Dihydroxyvitamin D3 activates secretion of hydrogen peroxide by human monocytes.

Human blood monocytes cultured in the presence of 1,25(OH)2D3 developed enhanced competence for secretion of H2O2 relative to cells suspended in media. This effect was maximal at a concentration of 10(-8) M 1,25(OH)2D3. After 3 days of incubation, monocyte-derived macrophages (MDM) exposed to 1,25(OH)2D3 demonstrated competence for secretion of H2O2 equivalent to cells exposed to recombinant IFN-gamma. Both IFN-gamma and 1,25(OH)2D3 offset decay of this function among cells in culture after 7 days. Simultaneous exposure of cells to 1,25(OH)2D3 and IFN-gamma did not activate competence for H2O2 secretion more than either agent alone. 24,25(OH)2D3 and 25(OH)2D3 activated MDM but at higher concentration than required for 1,25(OH)2D3. Progesterone did not affect H2O2 production. Incubation of MDM with a monoclonal antibody directed against IFN-gamma inhibited activation induced by lymphokine, and to a lesser extent by cells activated with IFN-gamma; this antibody had an insignificant effect on cells treated with 1,25(OH)2D3. These results suggest that 1,25(OH)2D3 exerts a receptor-mediated effect on monocyte function that results in cellular activation as manifested by enhanced competence for secretion of H2O2. It is possible that smaller concentrations of 1,25(OH)2D3 present in serum are permissive for macrophage activation, or that monocytic phagocytes are exposed to high concentrations of vitamin D metabolites under some clinical circumstances.

Photodynamic effects of erythrosine on the smooth muscle cells of guinea-pig taenia coli.

Photon activation of the halogenated fluorescein derivative erythrosine caused a marked calcium-dependent contraction of the smooth muscle cells of the guinea-pig taenia coli superfused in vitro. Neither high intensity illumination alone (up to 5 X 10(4) lux) nor erythrosine alone (up to 2 X 10(-4) M) altered the tone of the taenia or its ability to respond to carbachol (5 X 10(-5) M); photo-irradiation of erythrosine before tissue contact was also ineffective. The magnitude of the photodynamic contraction was dependent upon the concentration of erythrosine, the intensity and wavelength of the incident light, and the presence of oxygen; indirect effects via neurotransmitter release or cyclo-oxygenase activation were specifically excluded. The photodynamic response was blocked by zero-[Ca]o and addition of EGTA (1 mM) but not by omission of [Mg]o or a decrease in [Cl]o or [Na]o. D600 (methoxyverapamil) 10(-5) M, or a ten fold increase in [Mg]o, to 11.3 mM, partly inhibited the photodynamic contraction at low, but not high, light intensities. These observations are consistent with the following sequence of events: (i) photo-activation of the erythrosine molecule, (ii) the generation of highly reactive singlet oxygen, (iii) local peroxidation of cell membrane proteolipid, (iv) increased membrane permeability to Ca2+, (v) the influx of Ca2+ and, (vi) muscle contraction. It is concluded that the photodynamic action of erythrosine presents a novel method for modulation of membrane calcium permeability, and hence [Ca]i, not only in smooth muscle but possibly in other cells as well, e.g., secretory, epithelial and myocardial cells.