Predicting hospital cost in CKD patients through blood chemistry values

<p>Abstract</p> <p>Background</p> <p>Controversy exists in predicting costly hospitalization in patients with chronic kidney disease and co-morbid conditions. We therefore tested associations between serum chemistry values and the occurrence of in-patient hospital costs over a thirteen month study period. Secondarily, we derived a linear combination of variables to estimate probability of such occurrences in any patient.</p> <p>Method</p> <p>We calculated parsimonious values for select variables associated with in-patient hospitalization and compared sensitivity and specificity of these models to ordinal staging of renal disease.</p> <p>Data from 1104 de-identified patients which included 18 blood chemistry observations along with complete claims data for all medical expenses.</p> <p>We employed multivariable logistic regression for serum chemistry values significantly associated with in-patient hospital costs exceeding $3,000 in any single month and contrasted those results to other models by ROC area curves.</p> <p>Results</p> <p>The linear combination of weighted Z scores for parathyroid hormone, phosphorus, and albumin correlated with in-patient hospital care at p < 0.005. ROC curves derived from weighted variables of age, eGFR, hemoglobin, albumin, creatinine, and alanine aminotransferase demonstrated significance over models based on non-weighted Z scores for those same variables or CKD stage alone. In contrast, the linear combination of weighted PTH, PO4 and albumin demonstrated better prediction, but not significance over non-weighted Z scores for PTH alone.</p> <p>Conclusion</p> <p>Further study is justified to explore indices that predict costly hospitalization. Such metrics could assist Accountable Care Organizations in evaluating risk adjusted compensation for providers.</p

A common polymorphism of the human cardiac sodium channel alpha subunit (SCN5A) gene is associated with sudden cardiac death in chronic ischemic heart disease

Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio =1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association. © 2015 Marcsa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Estrogen receptor beta activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo

Estrogen receptor (ER)-β has been shown to possess a tumor suppressive effect, and is a potential target for cancer therapy. Using gene-expression meta-analysis of human malignant pleural mesothelioma, we identified an ESR2 (ERβ coding gene) signature. High ESR2 expression was strongly associated with low succinate dehydrogenase B (SDHB) (which encodes a mitochondrial respiratory chain complex II subunit) expression. We demonstrate that SDHB loss induced ESR2 expression, and that activated ERβ, by over-expression or by selective agonist stimulation, negatively affected oxidative phosphorylation compromising mitochondrial complex II and IV activity. This resulted in reduced mitochondrial ATP production, increased glycolysis dependence and impaired cell proliferation. The observed in vitro effects were phenocopied in vivo using a selective ERβ agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ERβ-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma