Pneumonia in Indiana Nursing Homes: A Retrospective Case Series

Background: The Optimizing Patient Transfers, Impacting Medical Quality, & Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project is a Centers for Medicare and Medicaid (CMS) demonstration project, tasked with reducing potentially avoidable hospitalizations of nursing home residents. OPTIMISTIC-enrolled nursing homes are reimbursed by CMS for treating residents with pneumonia in place. The purpose of this study is to examine the diagnosis, treatment, and outcomes of episodes of pneumonia in OPTIMISTIC nursing homes. Methods: This case series uses data from nursing home medical records of the seven facilities with the highest pneumonia caseload identified from the OPTIMISTIC database. Cases are from billing episodes spanning November 2017 through April 2018. Within each facility, cases of pneumonia were randomly selected for inclusion. Data were entered into an extraction tool designed by the study team. Results: Data were extracted from 41 records of unique patients. Despite CMS reimbursing for a maximum of 7 days for treatment of pneumonia, 78.0% of patients were monitored beyond that time and with greater attention than usual care. Of all 41 patients treated with antibiotics, 53.7% were given a fluoroquinolone and 24.4% were given amoxicillin/clavulanate. CURB-65 scores showed 58.3% scored in a range recommending hospitalization. Most patients (87.8%) were stabilized in the nursing home; three (7.3%) were hospitalized, one (2.4%) transferred to hospice, and one (2.4%) died. Conclusion: OPTIMISTIC-affiliated nursing facilities successfully provide enhanced care for most patients diagnosed with pneumonia in the facilities. Given the high incidence of fluoroquinolone use, one area for improvement is reduction of this medication contraindicated in the elderly

Pneumonia in Indiana nursing homes: a retrospective case series

Background  The Optimizing Patient Transfers, Impacting Medical Quality, & Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project is a Centers for Medicare and Medicaid (CMS) demonstration project, tasked with reducing potentially avoidable hospitalizations of nursing home residents. OPTIMISTIC-enrolled nursing homes are reimbursed by CMS for treating residents with pneumonia in place. The purpose of this study is to examine the diagnosis, treatment, and outcomes of episodes of pneumonia in OPTIMISTIC nursing homes.  Project Methods  This case series uses data from nursing home medical records of the seven facilities with the highest pneumonia caseload identified from the OPTIMISTIC database. Cases are from billing episodes spanning November 2017 through April 2018. Within each facility, cases of pneumonia were randomly selected for inclusion. Data were entered into an extraction tool designed by the study team.  Results  Data were extracted from 41 records of unique patients. Despite CMS reimbursing for a maximum of 7 days for treatment of pneumonia, 78.0% of patients were monitored beyond that time and with greater attention than usual care. Of all 41 patients treated with antibiotics, 53.7% were given a fluoroquinolone and 24.4% were given amoxicillin/clavulanate.  CURB-65 scores showed 58.3% scored in a range recommending hospitalization. Most patients (87.8%) were stabilized in the nursing home; three (7.3%) were hospitalized, one (2.4%) transferred to hospice, and one (2.4%) died.  Conclusion and Potential Impact  OPTIMISTIC-affiliated nursing facilities successfully provide enhanced care for most patients diagnosed with pneumonia in the facilities. Given the high incidence of fluoroquinolone use, one area for improvement is reduction of this medication contraindicated in the elderly

Discovering cancer genes by integrating network and functional properties

<p>Abstract</p> <p>Background</p> <p>Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI) data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO) annotations, to facilitate the identification of cancer genes.</p> <p>Methods</p> <p>Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1.</p> <p>Results</p> <p>Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs) with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1.</p> <p>Conclusion</p> <p>Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.</p

Regulation of the CNC-bZIP transcription factor Nrf2 by Keap1 and the axis between GSK-3 and β-TrCP

The transcription factor NF-E2 p45-related factor 2 (Nrf2) mediates adaptation to oxidative stress by inducing cytoprotective genes including heme oxygenase-1 (HMOX1) and NAD(P)H:quinone oxidoreductase-1 (NQO1). Nrf2 is principally controlled by Kelch-like ECH-associated protein 1 (Keap1), which allows constitutive ubiquitylation and rapid degradation of Nrf2 by the cullin-3 (Cul3)-RING ubiquitin ligase CRLKeap1 under non-stressed conditions. Simultaneously, glycogen synthase kinase-3 (GSK-3) also negatively controls Nrf2 through phosphorylation of a DSGIS-containing destruction motif in Nrf2, which then allows binding by β-transducin repeat-containing protein (β-TrCP) and ubiquitylation of the transcription factor by the Skp1−Cul1−F-box (SCF) ubiquitin ligase designated SCFβ-TrCP. It is well documented that oxidative stressors activate Nrf2 by antagonizing Keap1. We now show that both tert-butyl hydroquinone (tBHQ) and diethyl maleate (DEM), but not sulforaphane, induce Hmox1 and Nqo1 in Keap1−/− mouse embryonic fibroblasts (MEFs). Moreover, expression of Hmox1 and Nqo1 in Keap1−/− MEFs is substantially blunted by inhibition of either phosphoinositide 3-kinase (PI3K, using LY294002) or protein kinase B (PKB/Akt, using MK-2206), whereas inhibition of GSK-3 (using CT99021) induces expression of Hmox1 and Nqo1. Herein, we provide evidence that Nrf2 is subject to repression by both Keap1 and the axis between GSK-3 and β-TrCP. One likely scenario is that loss of the phosphatidylinositol (3,4,5)-trisphosphate (PIP3) 3-phosphatase activity of PTEN caused by tBHQ and DEM results in an increase in the levels of PIP3 produced by PI3K, and hence 3-phosphoinositide-dependent protein kinase-1 (PDK1) activity, which then stimulates PKB/Akt signaling.</p