Browsing by Author "Holmes, Ann M."

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    Correction: Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network
    (Springer Nature, 2019-07) Levy, Kenneth D.; Blake, Kathryn; Fletcher-Hoppe, Colette; Franciosi, James; Goto, Diasuke; Hicks, James K.; Holmes, Ann M.; Kanuri, Sri Harsha; Madden, Ebony B.; Musty, Michael D.; Orlando, Lori; Pratt, Victoria M.; Ramos, Michelle; Wu, Ryanne; Ginsburg, Geoffrey S.; Medicine, School of Medicine
    The original version of this Article contained an error in the spelling of the author Geoffrey S. Ginsburg, which was incorrectly given as Geoffrey Ginsburg. This has now been corrected in both the PDF and HTML versions of the Article.
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    Correction: Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network
    (Springer Nature, 2021) Levy, Kenneth D.; Blake, Kathryn; Fletcher-Hoppe, Colette; Franciosi, James; Goto, Daisuke; Hicks, James K.; Holmes, Ann M.; Kanuri, Sri Harsha; Madden, Ebony B.; Musty, Michael D.; Orlando, Lori; Pratt, Victoria M.; Ramos, Michelle; Wu, Ryanne; Ginsburg, Geoffrey S.; Medicine, School of Medicine
    Correction to: Genetics in Medicine 21:2019; 10.1038/s41436-018-0080-y; published online 12 July 2018 The original version of this Article contained an error in the spelling of the author Daisuke Goto, which was incorrectly given as Diasuke Goto. This has now been corrected in both the PDF and HTML versions of the Article.
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    Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real-world data
    (Nature, 2020-10) Limdi, Nita A.; Cavallari, Larisa H.; Lee, Craig R.; Hillegass, William B.; Holmes, Ann M.; Skaar, Todd C.; Pisu, Maria; Dillon, Chrisly; Beitelshees, Amber L.; Empey, Philip E.; Duarte, Julio D.; Diaby, Vakaramoko; Gong, Yan; Johnson, Julie A.; Graves, John; Garbett, Shawn; Zhou, Zilu; Peterson, Josh F.; Medicine, School of Medicine
    Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are traditionally grounded in clinical trial data. We conduct a CEA using real-world data using a 1-year decision-analytic model comparing primary strategies: universal empiric clopidogrel (base case), universal ticagrelor, and genotype-guided escalation. We also explore secondary strategies commonly implemented in practice, wherein all patients are prescribed ticagrelor for 30 days post PCI. After 30 days, all patients are switched to clopidogrel irrespective of genotype (nonguided de-escalation) or to clopidogrel only if patients do not harbor an LOF allele (genotype-guided de-escalation). Compared with universal clopidogrel, both universal ticagrelor and genotype-guided escalation were superior with improvement in quality-adjusted life years (QALY’s). Only genotype-guided escalation was cost-effective ($42,365/QALY) and demonstrated the highest probability of being cost-effective across conventional willingness-to-pay thresholds. In the secondary analysis, compared with the nonguided de-escalation strategy, although genotype-guided de-escalation and universal ticagrelor were more effective, with ICER of $188,680/QALY and $678,215/QALY, respectively, they were not cost-effective. CYP2C19 genotype-guided antiplatelet prescribing is cost-effective compared with either universal clopidogrel or universal ticagrelor using real-world implementation data. The secondary analysis suggests genotype-guided and nonguided de-escalation may be viable strategies, needing further evaluation.
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    CYP2D6 drug-gene and drug-drug-gene interactions among patients prescribed pharmacogenetically actionable opioids
    (Elsevier, 2017-12) Knisely, Mitchell R.; Carpenter, Janet S.; Burke Draucker, Claire; Skaar, Todd C.; Broome, Marion E.; Holmes, Ann M.; Von Ah, Diane; School of Nursing
    Purpose When codeine and tramadol are used for pain management, it is imperative that nurses are able to assess for potential drug-gene and drug-drug-gene interactions that could adversely impact drug metabolism and ultimately pain relief. Both drugs are metabolized through the CYP2D6 metabolic pathway which can be affected by medications as well the patient's own pharmacogenotype. The purpose of this brief report is to identify drug-gene and drug-drug-gene interactions in 30 adult patients prescribed codeine or tramadol for pain. Methods We used three data sources: (1) six months of electronic health record data on the number and types of medications prescribed to each patient; (2) each patient's CYP2D6 pharmacogenotype, and (3) published data on known CYP2D6 gene-drug and drug-drug-gene interactions. Results Ten patients (33%) had possible drug-gene or drug-drug-gene interactions. Five patients had CYP2D6 drug-gene interactions indicating they were not good candidates for codeine or tramadol. In addition, five patients had potential CYP2D6 drug-drug-gene interactions with either codeine or tramadol. Conclusion Our findings from this exploratory study underscores the importance of assessing and accounting for drug-gene and drug-drug-gene interactions in patients prescribed codeine or tramadol.
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    Does preventive dental care reduce non-preventive dental visits and expenditures among Medicaid-enrolled adults?
    (Wiley, 2022) Taylor, Heather L.; Sen, Bisakha; Holmes, Ann M.; Schleyer, Titus; Menachemi, Nir; Blackburn, Justin; Health Policy and Management, School of Public Health
    Objective To determine whether preventive dental visits are associated with fewer subsequent non-preventive dental visits and lower dental expenditures. Data Sources Indiana Medicaid enrollment and claims data (2015–2018) and the Area Health Resource File. Study design A repeated measures design with individual and year fixed effects examining the relationship between preventive dental visits (PDVs) and non-preventive dental visits (NPVs) and dental expenditures. Data Collection/Extraction Methods Not applicable. Principal findings Of 28,152 adults (108,349 observation-years) meeting inclusion criteria, 36.0% had any dental visit, 27.8% a PDV, and 22.1% a NPV. Compared to no PDV in the prior year, at least one was associated with fewer NPVs (β = −0.13; 95% CI -0.12, −0.11), lower NPV expenditures (β = −$29.12.53; 95% CI -28.07, −21.05), and lower total dental expenditures (−$70.12; 95% -74.92, −65.31), as well as fewer PDVs (β = −0.24; 95% CI -0.26, −0.23). Conclusions Our findings suggest that prior year PDVs are associated with fewer subsequent NPVs and lower dental expenditures among Medicaid-enrolled adults. Thus, from a public insurance program standpoint, supporting preventive dental care use may translate into improved population oral health outcomes and lower dental costs among certain low-income adult populations, but barriers to consistent utilization of PDV prohibit definitive findings.
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    Drug–gene and drug–drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial
    (Future Medicine, 2019-04) Fulton, Cathy R.; Zang, Yong; Desta, Zeruesenay; Rosenman, Marc B.; Holmes, Ann M.; Decker, Brian S.; Zhang, Yifei; Callaghan, John T.; Pratt, Victoria M.; Levy, Kenneth D.; Gufford, Brandon T.; Dexter, Paul R.; Skaar, Todd C.; Eadon, Michael T.; Medicine, School of Medicine
    Background: Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. Methods: This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). Results: Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19.0; 95% CI: 2.8-160.4) as compared with normal or indeterminate metabolizers (p = 0.01). After adjusting the CYP2D6 activity score for drug-drug interactions, uncontrolled pain was reported more frequently in individuals with reduced CYP2D6 activity (odds ratio: 0.50; 95% CI: 0.25-0.94). Conclusion: Phenoconversion for drug-drug and drug-gene interactions is an important consideration in pharmacogenomic implementation; drug-drug interactions may obscure the potential benefits of genotyping.
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    The Effects of Healthcare Service Disruptions on the Community, Healthcare Services and Access to Care
    (2022-08) Mills, Carol Ann; Blackburn, Justin; Holmes, Ann M.; Unroe, Kathleen; Yeager, Valerie A.
    Access to healthcare services is important for improving health outcomes, preventing and managing illness, and achieving health equity. The geographic maldistribution of physicians has a negative impact on rural areas compared to urban, particularly as it relates to access to healthcare. Rural hospitals have been closing or converting to another form of healthcare service at an increasing rate, adding another element to the existing complexities in rural access to care. Although a hospital closure in any location may have a considerable impact on the community, the closure of a rural hospital may have disproportionately more substantial implications for the economy and employment, health outcomes, and access to care. The contributing factors preceding rural hospital closures have been studied, but less is known about the full impact of rural hospital closures on the community. There is some evidence of shortages in healthcare providers and services, and therefore communities may employ multiple strategies to mitigate the shortages and provide services, including utilizing telehealth/virtual services. This dissertation proposes to examine the effects of rural hospital closures on the community, healthcare services, access to care, and provide a qualitative assessment of telehealth as a strategy to bridge gaps in provider access. This dissertation includes three studies: 1) a systematic review of the literature to examine the impact of rural hospital closures on the community; 2) an empirical study that utilizes a generalized difference in difference design with county and year fixed effects to estimate the relationship between rural hospital closures and nursing homes; and 3) a qualitative study exploring the perceptions and experiences of the nurses that piloted a virtual care support project, providing insights into crucial elements important to the implementation of similar models and the role of telehealth in bridging healthcare workforce gaps.
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    Employment Trends Among Public Health Doctoral Recipients, 2003-2015
    (American Public Health Association, 2018-09) Brown-Podgorski, Brittany L.; Holmes, Ann M.; Golembiewski, Elizabeth H.; Jackson, Joanna R.; Menachemi, Nir; Health Policy and Management, School of Public Health
    OBJECTIVES: To examine postgraduation employment trends among graduates of doctoral programs in public health from 2003 to 2015. METHODS: We analyzed pooled cross-sectional data from a census of graduates receiving a research doctorate from US accredited institutions. The outcome of interest was employment status. Covariates included public health discipline, sociodemographic characteristics, and institutional attributes. RESULTS: Of 11 771 graduates, nearly two thirds secured employment in either academic (34.8%) or nonacademic (31.4%) settings at the time of graduation. The proportion of those still seeking employment increased over time. Individuals who were White, younger, trained in either biostatistics or epidemiology, or from an institution with the highest level of research intensity were significantly more likely to secure employment. Academic employment was the most common setting for all 5 public health disciplines, but we observed differences in employment patterns (e.g., government, nonprofit, for-profit) across disciplines. CONCLUSIONS: Certain characteristics among public health doctoral recipients are correlated with postgraduation employment. More research is needed, but the observed increase in individuals still seeking employment may be attributable to increases in general public health graduates from for-profit institutions.
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    Enrollment of Diverse Populations in the INGENIOUS Pharmacogenetics Clinical Trial
    (Frontiers, 2020-06) Shah-Williams, Ebony; Levy, Kenneth D.; Zang, Yong; Holmes, Ann M.; Stoughton, Christa; Dexter, Paul; Skaar, Todd C.; Medicine, School of Medicine
    Recruitment of diverse populations and subjects living in Medically Underserved Areas and Populations (MUA/P’s) into clinical trials is a considerable challenge. Likewise, representation of African-Americans in pharmacogenetic trials is often inadequate, but critical for identifying genetic variation within and between populations. To identify enrollment patterns and variables that predict enrollment in a diverse underserved population, we analyzed data from the INGENIOUS (Indiana GENomics Implementation and Opportunity for the UnderServed), pharmacogenomics implementation clinical trial conducted at a community hospital for underserved subjects (Safety net hospital), and a statewide healthcare system (Academic hospital). We used a logistic regression model to identify patient variables that predicted successful enrollment after subjects were contacted and evaluated the reasons that clinical trial eligible subjects refused enrollment. In both healthcare systems, African-Americans were less likely to refuse the study than non-Hispanic Whites (Safety net, OR = 0.68, and p < 0.002; Academic hospital, OR = 0.64, and p < 0.001). At the Safety net hospital, other minorities were more likely to refuse the study than non-Hispanic Whites (OR = 1.58, p < 0.04). The odds of refusing the study once contacted increased with patient age (Safety net hospital, OR = 1.02, p < 0.001, Academic hospital, OR = 1.02, and p < 0.001). At the Academic hospital, females were less likely to refuse the study than males (OR = 0.81, p = 0.01) and those not living in MUA/P’s were less likely to refuse the study than those living in MUA/P’s (OR = 0.81, p = 0.007). The most frequent barriers to enrollment included not being interested, being too busy, transportation, and illness. A lack of trust was reported less frequently. In conclusion, African-Americans can be readily recruited to pharmacogenetic clinical trials once contact has been successfully initiated. However, health care initiatives and increased recruitment efforts of subjects living in MUA/Ps are needed. Enrollment could be further enhanced by improving research awareness and knowledge of clinical trials, reducing time needed for participation, and compensating for travel.
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    Examining the Impact of State-Mandated Insurance Benefits and Reimbursement Provisions on Access to Diabetes Self-Management Education and Training (DSME/T)
    (2019-09) Brown-Podgorski, Brittany L.; Vest, Joshua R.; deGroot, Mary K.; Holmes, Ann M.; Shi, Yunfeng; Simon, Kosali I.
    With an estimated 30.2 million diagnosed and undiagnosed cases among adults (and another 84 million at risk), diabetes mellitus is one of the most prevalent chronic conditions and a leading cause of mortality in the US. Diabetes self-management education and training (DSME/T) is a recognized standard of care and provides patients with the requisite knowledge and skills to properly manage the condition, improve long-term health outcomes, and reduce health care expenditures. Yet, DSME/T is greatly underutilized. Health insurance coverage that does not include benefits for DSME/T effectively imposes barriers to access for patients in need of the service. Many states have adopted laws and regulations requiring public and/or private insurers in their market to provide benefits for DSME/T; however, these requirements vary by state. It is unclear if these policies effectively improve access to DSME/T services. This dissertation seeks to rigorously assess the impact of state-mandated benefits and reimbursement provisions on access to DSME/T among adult patients with diabetes. The first analysis utilizes a unique combination of legal and programmatic data to quantify changes in the supply of DSME/T resources after the adoption of state-mandated benefits (potential access). The second analysis merges legal data with the Medical Expenditure Panel Survey (MEPS) from 2008 to 2016 to examine the impact of state mandates and reimbursement provisions on patient utilization of DSME/T (realized access). Lastly, the final analysis utilizes electronic health record data (2010-2016) from a safety net population to determine if patients’ evaluated need for DSME/T predicts the likelihood of receiving a DSME/T referral during a provider encounter (equitable access). Using novel data sources and a sophisticated policy analysis technique, this study provides a rigorous assessment of the impact of decades of state policies designed to improve access to care.