Motivated by the national evaluation of readmission rates among kidney dialysis facilities in the United States, we evaluate the impact of including discharging hospitals on the estimation of facility-level standardized readmission ratios (SRRs). The estimation of SRRs consists of two steps. First, we model the dependence of readmission events on facilities and patient-level characteristics, with or without an adjustment for discharging hospitals. Second, using results from the models, standardization is achieved by computing the ratio of the number of observed events to the number of expected events assuming a population norm and given the case-mix in that facility. A challenging aspect of our motivating example is that the number of parameters is very large and estimation of high-dimensional parameters is troublesome. To solve this problem, we propose a structured Newton-Raphson algorithm for a logistic fixed effects model and an approximate EM algorithm for the logistic mixed effects model. We consider a re-sampling and simulation technique to obtain p-values for the proposed measures. Finally, our method of identifying outlier facilities involves converting the observed p-values to Z-statistics and using the empirical null distribution, which accounts for overdispersion in the data. The finite-sample properties of proposed measures are examined through simulation studies. The methods developed are applied to national dialysis data. It is our great pleasure to present this paper in honor of Ross Prentice, who has been instrumental in the development of modern methods of modeling and analyzing life history and failure time data, and in the inventive applications of these methods to important national data problem.
Scaffold incorporated with affinity peptides can efficiently promote cartilage regeneration without exogenous addition of growth factors and cells.
Different forms of biomaterials, including microspheres, sponges, hydrogels, and nanofibers, have been broadly used in cartilage regeneration; however, effects of internal structures of the biomaterials on cells and chondrogenesis remain largely unexplored. We hypothesized that different internal structures of sponges and hydrogels led to phenotypic disparity of the cells and may lead to disparate chondrogenesis. In the current study, the chondrocytes in sponges and hydrogels of chitosan were compared with regard to cell distribution, morphology, gene expression, and production of extracellular matrix. The chondrocytes clustered or attached to the materials with spindle morphologies in the sponges, while they distributed evenly with spherical morphologies in the hydrogels. The chondrocytes proliferated faster with elevated gene expression of collagen type I and down-regulated gene expression of aggracan in sponges, when compared with those in the hydrogels. However, there was no significant difference of the expression of collagen type II between these two scaffolds. Excretion of both glycosaminoglycan (GAG) and collagen type II increased with time in vitro, but there was no significant difference between the sponges and the hydrogels. There was no significant difference in secretion of GAG and collagen type II in the two scaffolds, while the levels of collagen type I and collagen type X were much higher in sponges compared with those in hydrogels during an in vivo study. Though the chondrocytes displayed different phenotypes in the sponges and hydrogels, they led to comparable chondrogenesis. An optimized design of the biomaterials could further improve chondrogenesis through enhancing functionalities of the chondrocytes.
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