Browsing by Subject "Precision Medicine"

Now showing 1 - 10 of 11
  • Thumbnail Image
    Item
    ASN Presidential Address 2013: innovation and individualization--the path forward for nephrology
    (American Society for Nephrology, 2014-05) Molitoris, Bruce A.; Department of Medicine, IU School of Medicine
  • Thumbnail Image
    Item
    Characterization of hepatic enzyme activity in older adults with dementia: potential impact on personalizing pharmacotherapy
    (Dove Medical Press, 2015) Campbell, Noll L.; Skaar, Todd C.; Perkins, Anthony J.; Gao, Sujuan; Li, Lang; Khan, Babar A.; Boustani, Malaz A.; Department of Medicine, IU School of Medicine
    OBJECTIVE: To determine the frequency of pharmacogenomic variants and concurrent medications that may alter the efficacy and tolerability of acetylcholinesterase inhibitors (AChEIs). MATERIALS AND METHODS: A multisite cross-sectional study was carried out across four memory care practices in the greater Indianapolis area. Participants were adults aged 65 years and older with a diagnosis of probable or possible Alzheimer's disease (AD) (n=105). Blood samples and self-reported medication data were collected. Since two of the three AChEIs are metabolized by cytochrome P450 (CYP)-2D6, we determined the frequency of functional genetic variants in the CYP2D6 gene and calculated their predicted CYP2D6-activity scores. Concurrent medication data were collected from self-reported medication surveys, and their predicted effect on the pharmacokinetics of AChEIs was determined based on their known effects on CYP2D6 and CYP3A4/5 enzyme activities. RESULTS: Among the 105 subjects enrolled, 72% were female and 36% were African American. Subjects had a mean age of 79.6 years. The population used a mean of eight medications per day (prescription and nonprescription). The CYP2D6 activity score frequencies were 0 (3.8%), 0.5 (4.8%), 1.0 (36.2%), 1.5-2.0 (51.4%), and >2.0 (3.8%). Nineteen subjects (18.1%) used a medication considered a strong or moderate inhibitor of CYP2D6, and eight subjects (7.6%) used a medication considered a strong or moderate inhibitor of CYP3A4/5. In total, 28.6% of the study population was predicted to have reduced activity of the CYP2D6 or CYP3A4/5 enzymes due to either genetic variants or concomitant medications. CONCLUSION: Both pharmacogenetic variants and concurrent drug therapies that are predicted to alter the pharmacokinetics of AChEIs should be evaluated in older adults with AD. Pharmacogenetic and drug-interaction data may help personalize AD therapy and increase adherence by improving tolerability.
  • Thumbnail Image
    Item
    An Incremental Adoption Pathway for Developing Precision Medicine Based Healthcare Infrastructure for Underserved Settings
    (Medinfo 2017 Conference proceedings, 2017-08) Kasthurirathne, Suranga; Biondich, Paul; Mamlin, Burke; Cullen, Theresa; Grannis, Shaun
    Recent focus on Precision medicine (PM) has led to a flurry of research activities across the developed world. understaffed and underfunded health care systems in the US and elsewhere evolve to adapt PM to address pressing But how can healthcare needs? We offer guidance on a wide range of sources of healthcare data / knowledge sources as well as other infrastructure / tools that could inform PM initiatives, and may serve as low hanging fruit easily adapted on the incremental pathway towards a PM based healthcare system. Using these resources and tools, we propose an incremental adoption pathway to inform implementers working in underserved communities around the world on how they should position themselves to gradually embrace the concepts of PM with minimal interruption to existing care delivery.
  • Thumbnail Image
    Item
    Is personalized medicine achievable in obstetrics?
    (Elsevier - WB Saunders, 2014-12) Quinney, Sara K.; Patil, Avinash S.; Flockhart, David A.; Department of Obstetrics and Gynecology, IU School of Medicine
    Personalized medicine seeks to identify the right dose of the right drug for the right patient at the right time. Typically, individualization of therapy is based on the pharmacogenomic makeup of the individual and environmental factors that alter drug disposition and response. In addition to these factors, during pregnancy, a woman's body undergoes many changes that can impact the therapeutic efficacy of medications. Yet, there is minimal research regarding personalized medicine in obstetrics. Adoption of pharmacogenetic testing into the obstetrical care is dependent on evidence of analytical validity, clinical validity, and clinical utility. Here, we briefly present information regarding the potential utility of personalized medicine for treating the obstetric patient for pain with narcotics, hypertension, and preterm labor, and discuss the impediments of bringing personalized medicine to the obstetrical clinic.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Pharmacogenetics and individualizing drug treatment during pregnancy
    (Future Medicine, 2014-01) Haas, David M.; Department of Obstetrics and Gynecology, IU School of Medicine
    Pharmacogenetics as a tool to aid clinicians implement individualized pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in pregnancy is still a developing field. However, there are several areas of obstetric therapeutics where data are emerging that give glimpses into future therapeutic possibilities. These include opioid pain management, antihypertensive therapy, antidepressant medications, preterm labor tocolytics, antenatal corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few. More data are needed to populate the therapeutic models and to truly determine if pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The objective of this review is to summarize current data and highlight research needs.
  • Thumbnail Image
    Item
    Pharmacotherapy and pregnancy: Highlights from the first International Conference for Individualized Pharmacotherapy in Pregnancy
    (Wiley, 2009-02) Haas, David M.; Renbarger, Jamie L.; Denne, Scott; Ahmed, Mahmoud S.; Easterling, Thomas; Feibus, Karen; Meslin, Eric M.; Koren, Gideon; Zajicek, Anne; Snodgrass, Wayne R.; Flockhart, David A.; Medicine, School of Medicine
    Data are sparse on the effects of medication use during pregnancy. Half of the world's population is women. The majority of women become pregnant, and many of those women take some kind of medication during their pregnancy, even if only for a short time. The majority of drugs have not been rigorously studied in pregnant women to determine the most effective dose with the least potential for adverse effects. Instead, women are given “cookie‐cutter” therapy, using doses extrapolated from nonpregnant women, men, or pregnant animals. This can lead to problems. Instead, individualization of pharmacotherapy in pregnancy promises to take individual women and determine the optimal dose and drug for them to maximize the effect of the drug while attempting to minimize the side effects to them and their unborn babies. Because this field of study is underrepresented, we held a conference to bring together researchers and experts to discuss current knowledge, issues, and challenges surrounding individualized pharmacotherapy in pregnancy. Speakers came from the NIH, the Food and Drug Administration (FDA), and various research centers in the United States and Canada. Below are the summaries of the discussions at the conference. Full notes from the panel discussions are available from the authors on request.
  • Thumbnail Image
    Item
    Plain-language medical vocabulary for precision diagnosis
    (Nature Research, 2018-04) Vasilevsky, Nicole A.; Foster, Erin D.; Engelstad, Mark E.; Carmody, Leigh; Might, Matt; Chambers, Chip; Dawkins, Hugh J. S.; Lewis, Janine; Della Rocca, Maria G.; Snyder, Michelle; Boerkoel, Cornelius F.; Rath, Ana; Terry, Sharon F.; Kent, Alastair; Searle, Beverly; Baynam, Gareth; Jones, Erik; Gavin, Pam; Bamshad, Michael; Chong, Jessica; Groza, Tudor; Adams, David; Resnick, Adam C.; Heath, Allison P.; Mungall, Chris; Holm, Ingrid A.; Rageth, Kayli; Brownstein, Catherine A.; Shefchek, Kent; McMurry, Julie A.; Robinson, Peter N.; Köhler, Sebastian; Haendel, Melissa A.; Medicine, School of Medicine
  • Thumbnail Image
    Item
    The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: an overview of Network organization, procedures and interventions
    (Elsevier, 2022-02) Georas, Steve N.; Wright, Rosalind J.; Ivanova, Anastasia; Israel, Elliot; LaVange, Lisa M.; Akuthota, Praveen; Carr, Tara F.; Denlinger, Loren C.; Fajt, Merritt L.; Kumar, Rajesh; O’Neal, Wanda K.; Phipatanakul, Wanda; Szefler, Stanley J.; Aronica, Mark A.; Bacharier, Leonard B.; Burbank, Allison J.; Castro, Mario; Alexander, Laura Crotty; Bamdad, Julie; Cardet, Juan Carlos; Comhair, Suzy A. A.; Covar, Ronina A.; DiMango, Emily A.; Erwin, Kim; Erzurum, Serpil C.; Fahy, John V.; Gaffin, Jonathan M.; Gaston, Benjamin; Gerald, Lynn B.; Hoffman, Eric A.; Holguin, Fernando; Jackson, Daniel J.; James, John; Jarjour, Nizar N.; Kenyon, Nicholas J.; Khatri, Sumita; Kirwan, John P.; Kraft, Monica; Krishnan, Jerry A.; Liu, Andrew H.; Liu, Mark C.; Marquis, M. Alison; Martinez, Fernando; Mey, Jacob; Moore, Wendy C.; Moy, James N.; Ortega, Victor E.; Peden, David B.; Pennington, Emily; Peters, Michael C.; Ross, Kristie; Sanchez, Maria; Smith, Lewis J.; Sorkness, Ronald L.; Wechsler, Michael E.; Wenzel, Sally E.; White, Steven R.; Zein, Joe; Zeki, Amir A.; Noel, Patricia; Pediatrics, School of Medicine
    Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here we describe the Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the U.S. The PrecISE Network was designed to conduct phase II/proof of concept clinical trials of precision interventions in the severe asthma population, and is supported by the National Heart Lung and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the Network will evaluate up to six interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for of severe asthma.
  • Thumbnail Image
    Item
    Prerequisites to Implementing a Pharmacogenomics Program in a Large Healthcare System
    (Nature Publishing Group, 2014-09) Levy, KD; Decker, BS; Carpenter, JS; Flockhart, DA; Dexter, PR; Desta, Z; Skaar, Todd C.; Department of Medicine, Division of Clinical Pharmacology, IU School of Medicine