Publications by authors named "Lindsay Hines"

9 Publications

  • Page 1 of 1

Impact of Automated Best Practice Advisories on Provider Response to Genotyping Results for Patients on Clopidogrel.

J Pharm Pract 2021 Oct 8:8971900211049589. Epub 2021 Oct 8.

Department of Neuropsychology, 24195Sanford Health, Fargo, ND, USA.

ObjectiveThe study objective was to examine provider acceptance and genotyping responses to a best practice advisory (BPA) concerning clopidogrel and intermediate and poor metabolizers within the context of a new pharmacogenomics program at a Midwestern health system Other secondary objectives analyzed included appropriate BPA firing, the distribution of alleles in study population, indications for clopidogrel use, and impact of indication on therapy change. In this study, the progress of this program was assessed by quantifying how providers respond to BPAs generated in the electronic medical record (EMR), in the context of a single representative gene-drug-outcome relationship. Patient data was pulled via reports yielding patients with genotyped information in the EMR and cross-referenced with a report evaluating BPA firing occurrences. By capturing antiplatelet therapy changes in response to genotyping results, 37 patients were found that had 73 BPAs fire. Nine of those patients had alternative antiplatelet therapy ordered. Of these, 6 alternative antiplatelet therapies were ordered from the BPA. Providers utilized BPAs, but responded differently based on individual knowledge of genotypes and indications. Information obtained from this study can be used for provider education and as reference for future design and wording of BPAs.
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http://dx.doi.org/10.1177/08971900211049589DOI Listing
October 2021

genotype, physician prescribing pattern, and risk for long QT on serotonin selective reuptake inhibitors.

Pharmacogenomics 2019 04 15;20(5):343-351. Epub 2019 Apr 15.

Department of Neuropsychology, Sanford Health, Fargo, ND 58122, USA.

To examine the impact of  genotype on selective serotonin reuptake inhibitor (SSRI) prescribing patterns. : Observational cohort containing 507 unique individuals receiving an SSRI prescription with genotype already in their electronic medical record. Genotype was distributed as follows: n = 360 (71%) had no loss of function alleles, 136 (26.8%) had one loss of function allele and 11 (2.2%) had two loss of function alleles. For poor metabolizers exposed to sertraline, citalopram or escitalopram, providers changed prescribing patterns in response to alerts in the electronic medical record by either changing the drug, changing the dose or monitoring serial EKGs longitudinally. For intermediate metabolizers exposed to sertraline, citalopram or escitalopram, no alert was needed (mean QTc = 440.338 ms [SD = 31.1273] for , mean QTc = 440.371 ms [SD = 29.2706] for ; p = 0.995).
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http://dx.doi.org/10.2217/pgs-2018-0156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562837PMC
April 2019

Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing.

Genet Med 2019 10 21;21(10):2255-2263. Epub 2019 Mar 21.

Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.

Purpose: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers.

Methods: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned.

Results: Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability.

Conclusion: There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs.
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http://dx.doi.org/10.1038/s41436-019-0484-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754805PMC
October 2019

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

JACC Cardiovasc Interv 2018 01 1;11(2):181-191. Epub 2017 Nov 1.

Department of Medicine, University of Maryland, Baltimore, Maryland.

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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http://dx.doi.org/10.1016/j.jcin.2017.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775044PMC
January 2018

Point-Counterpoint: Genotyping for SSRIs.

S D Med 2017 Jun;70(6):246-248

University of North Dakota.

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June 2017

Navigating pleiotropy in precision medicine: pharmacogenes from trauma to behavioral health.

Pharmacogenomics 2016 Apr 29;17(5):499-505. Epub 2016 Mar 29.

Department of Internal Medicine, University of South Dakota Sanford School of Medicine, 1400 West 22nd Street, Sioux Falls, SD 57105, USA.

A strong emerging principle in the field of precision medicine is that variation in any one pharmacogene may impact clinical outcome for more than one drug. Variants tested in the acute care setting often have downstream implications for other drugs impacting chronic disease management. A flexible framework is needed as clinicians and scientists move toward deploying automated decision support for gene-based drug dosing in electronic medical records.
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http://dx.doi.org/10.2217/pgs.16.6DOI Listing
April 2016

Cortical brain atrophy and intra-individual variability in neuropsychological test performance in HIV disease.

Brain Imaging Behav 2016 09;10(3):640-51

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV-) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIVd was measured by computing intra-individual standard deviations (ISD's) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Total gray matter (GM) volume was inversely associated with IIVd. Among all subjects, IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIVd -related GM atrophy. IIVd in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests.
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http://dx.doi.org/10.1007/s11682-015-9441-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767700PMC
September 2016

Depression, cognition, and self-appraisal of functional abilities in HIV: an examination of subjective appraisal versus objective performance.

Clin Neuropsychol 2011 Feb;25(2):224-43

Semel Institute for Neuroscience and Human Behavior, School of Medicine, University of California-Los Angeles, CA 90095, USA.

Depression frequently co-occurs with HIV infection and can result in self-reported overestimates of cognitive deficits. Conversely, genuine cognitive dysfunction can lead to an under-appreciation of cognitive deficits. The degree to which depression and cognition influence self-report of capacity for instrumental activities of daily living (IADLs) requires further investigation. This study examined the effects of depression and cognitive deficits on self-appraisal of functional competence among 107 HIV-infected adults. As hypothesized, higher levels of depression were found among those who over-reported problems in medication management, driving, and cognition when compared to those who under-reported or provided accurate self-assessments. In contrast, genuine cognitive dysfunction was predictive of under-reporting of functional deficits. Together, these results suggest that over-reliance on self-reported functional status poses risk for error when diagnoses require documentation of both cognitive impairment and associated functional disability in everyday life.
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http://dx.doi.org/10.1080/13854046.2010.539577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616492PMC
February 2011

Medication and finance management among HIV-infected adults: the impact of age and cognition.

J Clin Exp Neuropsychol 2011 Feb 6;33(2):200-9. Epub 2010 Aug 6.

UCLA School of Medicine, Los Angeles, CA 90024,

This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report.
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http://dx.doi.org/10.1080/13803395.2010.499357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616485PMC
February 2011
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