An integrated approach to prognosis using protein microarrays and nonparametric methods

Over the past several years, multivariate approaches have been developed that address the problem of disease diagnosis. Here, we report an integrated approach to the problem of prognosis that uses protein microarrays to measure a focused set of molecular markers and non-parametric methods to reveal non-linear relationships among these markers, clinical variables, and patient outcome. As proof-of-concept, we applied our approach to the prediction of early mortality in patients initiating kidney dialysis. We found that molecular markers are not uniformly prognostic, but instead vary in their value depending on a combination of clinical variables. This may explain why reports in this area aiming to identify prognostic markers, without taking into account clinical variables, are either conflicting or show that markers have marginal prognostic value. Just as treatments are now being tailored to specific subsets of patients, our results show that prognosis can also benefit from a ‘personalized' approach

Fibrosis in the kidney: is a problem shared a problem halved?

Fibrotic disorders are commonplace, take many forms and can be life-threatening. No better example of this exists than the progressive fibrosis that accompanies all chronic renal disease. Renal fibrosis is a direct consequence of the kidney's limited capacity to regenerate after injury. Renal scarring results in a progressive loss of renal function, ultimately leading to end-stage renal failure and a requirement for dialysis or kidney transplantation

The importance of iron in long-term survival of maintenance hemodialysis patients treated with epoetin-alfa and intravenous iron: analysis of 9.5 years of prospectively collected data

<p>Abstract</p> <p>Background</p> <p>In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial. The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron, and of hemoglobin and variables related to iron status.</p> <p>Methods</p> <p>The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York, NY from January 1998 to June, 2007. A patient-centered, coded, electronic patient record used in patient care enabled retrospective analysis of data collected prospectively. For survival analysis, patients were censored when transplanted, transferred to hemodialysis at home or elsewhere, peritoneal dialysis. Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox's regression, using as variables age, race, gender, major co-morbid conditions, epoetin-alfa and intravenous iron administered, and 15 laboratory tests.</p> <p>Results</p> <p>Median age was 59 years, epoetin-alfa (interquartile range) 18,162 (12,099, 27,741) units/week, intravenous iron 301 (202, 455) mg/month, survival 789 (354, 1489) days. Median hemoglobin was 116 (110, 120)g/L, transferrin saturation 29.7 (24.9, 35.1)%, serum ferritin 526 (247, 833) μg/L, serum albumin 39.0 (36.3, 41.5) g/L. Survival was better the higher the hemoglobin, best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron. For intravenous iron, survival was best with 1–202 mg/month, slightly worse with 202–455 mg/month; it was worst with no intravenous iron, only slightly better with > 455 mg/month. Survival was worst with transferrin saturation ≤ 16%, serum ferritin ≤ 100 μg/L, best with transferrin saturation > 25%, serum ferritin > 600 μg/L The effects of each of hemoglobin, intravenous iron, transferrin saturation, and serum ferritin on survival were independently significant and not mediated by other predictors in the model.</p> <p>Conclusion</p> <p>Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level, by moderate intravenous iron administration, and by indicators of iron sufficiency. It was unfavorably influenced by a low hemoglobin level, and by indicators of iron deficiency.</p

Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients – the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]

BACKGROUND: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. METHODS: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. CONCLUSION: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD

Bismarck or Beveridge: a beauty contest between dinosaurs

<p>Abstract</p> <p>Background</p> <p>Health systems delivery systems can be divided into two broad categories: National Health Services (NHS) on the one hand and Social Security (based) Health care systems (SSH) on the other hand. Existing literature is inconclusive about which system performs best. In this paper we would like to improve the evidence-base for discussion about pros and cons of NHS-systems versus SSH-system for health outcomes, expenditure and population satisfaction.</p> <p>Methods</p> <p>In this study we used time series data for 17 European countries, that were characterized as either NHS or SSH country. We used the following performance indicators: For health outcome: overall mortality rate, infant mortality rate and life expectancy at birth. For health care costs: health care expenditure per capita in pppUS$ and health expenditure as percentage of GDP. Time series dated from 1970 until 2003 or 2004, depending on availability. Sources were OECD health data base 2006 and WHO health for all database 2006. For satisfaction we used the Eurobarometer studies from 1996, 1998 and 1999.</p> <p>Results</p> <p>SSH systems perform slightly better on overall mortality rates and life expectancy (after 1980). For infant mortality the rates converged between the two types of systems and since 1980 no differences ceased to exist.</p> <p>SSH systems are more expensive and NHS systems have a better cost containment. Inhabitants of countries with SSH-systems are on average substantially more satisfied than those in NHS countries.</p> <p>Conclusion</p> <p>We concluded that the question 'which type of system performs best' can be answered empirically as far as health outcomes, health care expenditures and patient satisfaction are concerned. Whether this selection of indicators covers all or even most relevant aspects of health system comparison remains to be seen. Perhaps further and more conclusive research into health system related differences in, for instance, equity should be completed before the leading question of this paper can be answered. We do think, however, that this study can form a base for a policy debate on the pros and cons of the existing health care systems in Europe.</p