Browsing by Author "Decker, Brian"

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    Analytical validity of a genotyping assay for use with personalized antihypertensive and chronic kidney disease therapy
    (Wolters Kluwer, 2019-01) Collins, Kimberly; Pratt, Victoria; Stansberry, Wesley; Medeiros, Elizabeth; Kannegolla, Karthik; Swart, Marelize; Skaar, Todd C.; Chapman, Arlene; Decker, Brian; Moorthi, Ranjani; Eadon, Michael; Medicine, School of Medicine
    Hypertension and chronic kidney disease are inextricably linked. Hypertension is a well-recognized contributor to chronic kidney disease progression and, in turn, renal disease potentiates hypertension. A generalized approach to drug selection and dosage has not proven effective in managing these conditions, in part, because patients with heterogeneous kidney disease and hypertension etiologies are frequently grouped according to functional or severity classifications. Genetic testing may serve as an important tool in the armamentarium of clinicians who embrace precision medicine. Increasing scientific evidence has supported the utilization of genomic information to select efficacious antihypertensive therapy and understand hereditary contributors to chronic kidney disease progression. Given the wide array of antihypertensive agents available and diversity of genetic renal disease predictors, a panel-based approach to genotyping may be an efficient and economic means of establishing an individualized blood pressure response profile for patients with various forms of chronic kidney disease and hypertension. In this manuscript, we discuss the validation process of a Clinical Laboratory Improvement Amendments (CLIA)-approved genetic test to relay information on 72 genetic variants associated with kidney disease progression and hypertension therapy. These genomic-based interventions, in addition to routine clinical data, may help inform physicians to provide personalized therapy.
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    Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing
    (Wiley, 2015-07) Birdwell, Kelly A.; Decker, Brian; Barbarino, Julia M.; Peterson, Josh F.; Stein, C. Michael; Sadee, Wolfgang; Wang, Danxin; Vinks, Alexander A.; He, Yijing; Swen, Jesse J.; Leeder, J. Steven; van Schaik, RHN; Thummel, Kenneth E.; Klein, Teri E.; Caudle, Kelly E.; MacPhee, Iain A.M.; Department of Medicine, IU School of Medicine
    Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).
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    Kidney Mentoring and Assessment Program for Students: a guide for engaging medical students in nephrology
    (Oxford University Press, 2019-12) Bayliss, George P.; Cobb, Jason; Decker, Brian; Hellman, Richard; Vasavada, Nina; Mackelaite, Lina; Shadur, Craig; Ilori, Titilayo; Ibrahim, Tod; Leight, Katlyn; Hsiao, Li-Li; Molitoris, Bruce A.; Okusa, Mark D.; Parker, Mark G.; Medicine, School of Medicine
    Background The American Society of Nephrology’s (ASN) Workforce Committee created a unique program called the Kidney Mentoring and Awareness Program for Students to engage medical students in the fight against kidney diseases and interest them in careers in nephrology. Methods The program provided a framework and 2 years of funding to three medical schools to organize and carry out health screenings in underserved areas of their communities as well as a structure for student mentoring by the practicing nephrologists. Results The Workforce Committee identified three medical schools (Emory University, Atlanta, GA; Indiana University, Indianapolis, IN and University of Louisville, Louisville, KY) and engaged faculty at each school to serve as advisors. The ASN committed funding to the groups for 2 years, after which the groups became self-sufficient. Three nephrologists participated in each chapter, building on existing relationships with community groups to identify sites and carry out kidney screening events. Conclusions We report here the experience of those chapters and a blueprint for other schools interested in setting up a similarly structured program to interest students in nephrology while working with community groups to spread awareness of the major underlying causes of kidney disease.
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    Lessons Learned When Introducing Pharmacogenomic Panel Testing into Clinical Practice
    (Elsevier, 2017-01-01) Rosenman, Marc B.; Decker, Brian; Levy, Kenneth D.; Holmes, Ann M.; Pratt, Victoria M.; Eadon, Michael T.; Medicine, School of Medicine
    Objectives: Implementing new programs to support precision medicine in clinical settings is a complex endeavor. We describe challenges and potential solutions based on the Indiana GENomics Implementation: an Opportunity for the Underserved (INGenious) program at Eskenazi Health-one of six sites supported by the Implementing GeNomics In pracTicE network grant of the National Institutes of Health/National Human Genome Research Institute. INGenious is an implementation of a panel of genomic tests. Methods: We conducted a descriptive case study of the implementation of this pharmacogenomics program, which has a wide scope (14 genes, 27 medications) and a diverse population (patients who often have multiple chronic illnesses, in a large urban safety-net hospital and its outpatient clinics). Challenges: We placed the clinical pharmacogenomics implementation challenges into six categories: patient education and engagement in care decision making; clinician education and changes in standards of care; integration of technology into electronic health record systems; translational and implementation sciences in real-world clinical environments; regulatory and reimbursement considerations, and challenges in measuring outcomes. A cross-cutting theme was the need for careful attention to workflow. Our clinical setting, a safety-net health care system, presented some distinctive challenges. Patients often had multiple chronic illnesses and sometimes were taking more than one pharmacogenomics-relevant medication. Reaching patients for recruitment or follow-up was another challenge. Conclusions: New, large-scale endeavors in health care are challenging. A description of the challenges that we encountered and the approaches that we adopted to address them may provide insights for those who implement and study innovations in other health care systems.
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    Quantitative Intravital Microscopy of Liver Transport
    (Office of the Vice Chancellor for Research, 2013-04-05) Ryan, Jennifer; Ghabril, Marwan; Decker, Brian; Dunn, Kenneth W.
    Because if its unique ability to collect fluorescence images from deep in biological tissues, intravital multiphoton microscopy has become a valuable tool in several areas of biological research, including neurobiology, cancer biology and immunology. Here we describe methods of quantitative intravital microscopy that we have developed to characterize cholestatic liver injury. Special methods of tissue immobilization, multiphoton microscopy and digital image analysis were developed to support dynamic measurements of the kinetics of transport from the sinusoids into the cytosol and from the cytosol into the bile canaliculi in individual hepatocytes in vivo. Using a combination of different fluorescent probes, we have combined transport assays with measures of microvascular function, inflammation and cell viability to provide integrated measures of liver injury. The sensitivity of this approach is demonstrated in quantitative analyses of the acute effects of cholestatic drugs and the effects of chronic kidney disease.