Browsing by Author "Nelson, David R."

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    An integrated clinico-metabolomic model improves prediction of death in sepsis
    (American Association for the Advancement of Science, 2013) Langley, Raymond J.; Tsalik, Ephraim L.; van Velkinburgh, Jennifer C.; Glickman, Seth W.; Rice, Brandon J.; Wang, Chunping; Chen, Bo; Carin, Lawrence; Suarez, Arturo; Mohney, Robert P.; Freeman, Debra H.; Wang, Mu; You, Jinsam; Wulff, Jacob; Thompson, J. Will; Moseley, M. Arthur; Reisinger, Stephanie; Edmonds, Brian T.; Grinnell, Brian; Nelson, David R.; Dinwiddie, Darrell L.; Miller, Neil A.; Saunders, Carol J.; Soden, Sarah S.; Rogers, Angela J.; Gazourian, Lee; Fredenburgh, Laura E.; Massaro, Anthony F.; Baron, Rebecca M.; Choi, Augustine M. K.; Corey, G. Ralph; Ginsburg, Geoffrey S.; Cairns, Charles B.; Otero, Ronny M.; Fowler, Vance G., Jr.; Rivers, Emanuel P.; Woods, Christopher W.; Kingsmore, Stephen F.; Medicine, School of Medicine
    Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would ultimately die differed markedly from those of patients who would survive. The different profiles of proteins and metabolites clustered into the following groups: fatty acid transport and β-oxidation, gluconeogenesis, and the citric acid cycle. They differed consistently among several sets of patients, and diverged more as death approached. In contrast, the metabolomes and proteomes of surviving patients with mild sepsis did not differ from survivors with severe sepsis or septic shock. An algorithm derived from clinical features together with measurements of five metabolites predicted patient survival. This algorithm may help to guide the treatment of individual patients with sepsis.
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    Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention
    (Elsevier, 2018-01-22) Cavallari, Larisa H.; Lee, Craig R.; Beitelshees, Amber L.; Cooper-DeHoff, Rhonda M.; Duarte, Julio D.; Voora, Deepak; Kimmel, Stephen E.; McDonough, Caitrin W.; Gong, Yan; Dave, Chintan V.; Pratt, Victoria M.; Alestock, Tameka D.; Anderson, R. David; Alsip, Jorge; Ardati, Amer K.; Brott, Brigitta C.; Brown, Lawrence; Chumnumwat, Supatat; Clare-Salzler, Michael J.; Coons, James C.; Denny, Joshua C.; Dillon, Chrisly; Elsey, Amanda R.; Hamadeh, Issam; Harada, Shuko; Hillegass, William B.; Hines, Lindsay; Horenstein, Richard B.; Howell, Lucius A.; Jeng, Linda J.B.; Kelemen, Mark D.; Lee, Y.M.; Magvanjav, Oyunbileg; Montasser, May; Nelson, David R.; Nutescu, Edith A.; Nwaba, Devon C.; Pakyz, Ruth E.; Palmer, Kathleen; Peterson, Josh F.; Pollin, Toni I.; Quinn, Alison H.; Robinson, Shawn W.; Schub, Jamie; Skaar, Todd C.; Smith, Donald M.; Sriramoju, Vindhya B.; Starostik, Petr; Stys, Tomasz P.; Stevenson, James M.; Varunok, Nicholas; Vesely, Mark R.; Wake, Dyson T.; Weck, Karen E.; Weitzel, Kristin W.; Wilke, Russell A.; Willig, James; Zhao, Richard Y.; Kreutz, Rolf P.; Stouffer, George A.; Empey, Philip E.; Limdi, Nita A.; Shuldiner, Alan R.; Winterstein, Almut G.; Johnson, Julie A.; Medical and Molecular Genetics, School of Medicine
    OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
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    Trends in Depressed Mood and Suicidal Behaviors Among Female High School Students Who Engaged in Physical Fighting
    (Sage, 2019) Ford, Janet H.; Zollinger, Terrell W.; Zhang, Jianjun; O'Neil, Joseph; Nelson, David R.; Steele, Gregory K.; Epidemiology, School of Public Health
    The objective of this article is to identify prevalence changes in depressed mood/suicidal behaviors among female high school students reporting physical fighting. This research analyzed the national combined data set of the Youth Risk Behavior Surveillance (YRBS) cross-sectional surveys from 2001 to 2015. Logistic regression analyzed the time trends. Two multiple logistic regression models were built. A quadratic trend was present with an initial decrease followed by an increase 2009 to 2015 (p < .001). The odds and severity of depressed mood/suicidal behaviors were greater among female youths with four or more fights and for other violent events, which were even greater when accounting for electronic bullying. The odds of depressed mood/suicidal behaviors among female adolescents engaged in physical fighting has been increasing with electronic bullying contributing to polyvictimization.