C Adrian Austin1,2, Andy Szeto3, Apoorva Gupta4, Timothy Wiltshire3,5, Daniel J Crona3,5,6, Christine Kistler2,7,8. 1. Division of Pulmonary and Critical Care Medicine, Division of Geriatric Medicine, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 2. Division of Geriatric Medicine, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 3. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 4. School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 5. UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA. 6. Department of Pharmacy, UNC Hospitals and Clinics, Chapel Hill, NC, USA. 7. Department of Family Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 8. The Cecil G. Sheps Center for Health Services Research, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Abstract
Background: Pharmacogenetics may explain a substantial proportion of the variation seen in the efficacy and risk profile of analgesosedative drugs and the incidence of delirium in critically ill adults. Objectives: Conduct a feasibility study to demonstrate the reliability of collecting and analyzing pharmacogenetic information from critically ill patients and to assess the impact of pharmacogenetics on intensive care unit (ICU) outcomes. Methods: We prospectively enrolled subjects from the Medical ICU at the University of North Carolina (UNC). DNA was obtained via a buccal swab and evaluated using the DNA2Rx assay. We collected data on demographics, daily cumulative psychoactive medication exposure, and severity of illness. We performed daily delirium assessments via the CAM-ICU. We analyzed associations between select single nucleotide polymorphisms (SNPs) and delirium. Results: From June, 2018 through January, 2019, we screened 244 patients and enrolled 50. The median age was 62.0 years old (range: 28-82 years old), and 27 (54%) of the subjects were female. In all, 49 (98%) samples were both high quality and sufficient quantity. In secondary analyses, we found that 80% (12/15) of patients with two 2 copies of a G allele at rs4680 on COMT experienced delirium, whereas 44% (4/9) of patients with 2 copies of an A allele at this location had delirium. In all, 44% (4/9) of patients with 2 T allele copies at rs7439366 on UGT2B7 experienced delirium compared to 73% (11/15) of patients with 2 C allele copies at this location. Conclusions: We can feasibly collect genetic information from critically ill adults. We were able to efficiently collect high quality DNA of sufficient quantity to conduct pharmacogenetic analysis in this critically ill population. Although the sample size of our current study is too small to conduct robust inferential analyses, it suggests potential SNP targets for a future larger study.
Background: Pharmacogenetics may explain a substantial proportion of the variation seen in the efficacy and risk profile of analgesosedative drugs and the incidence of delirium in critically ill adults. Objectives: Conduct a feasibility study to demonstrate the reliability of collecting and analyzing pharmacogenetic information from critically ill patients and to assess the impact of pharmacogenetics on intensive care unit (ICU) outcomes. Methods: We prospectively enrolled subjects from the Medical ICU at the University of North Carolina (UNC). DNA was obtained via a buccal swab and evaluated using the DNA2Rx assay. We collected data on demographics, daily cumulative psychoactive medication exposure, and severity of illness. We performed daily delirium assessments via the CAM-ICU. We analyzed associations between select single nucleotide polymorphisms (SNPs) and delirium. Results: From June, 2018 through January, 2019, we screened 244 patients and enrolled 50. The median age was 62.0 years old (range: 28-82 years old), and 27 (54%) of the subjects were female. In all, 49 (98%) samples were both high quality and sufficient quantity. In secondary analyses, we found that 80% (12/15) of patients with two 2 copies of a G allele at rs4680 on COMT experienced delirium, whereas 44% (4/9) of patients with 2 copies of an A allele at this location had delirium. In all, 44% (4/9) of patients with 2 T allele copies at rs7439366 on UGT2B7 experienced delirium compared to 73% (11/15) of patients with 2 C allele copies at this location. Conclusions: We can feasibly collect genetic information from critically ill adults. We were able to efficiently collect high quality DNA of sufficient quantity to conduct pharmacogenetic analysis in this critically ill population. Although the sample size of our current study is too small to conduct robust inferential analyses, it suggests potential SNP targets for a future larger study.
Authors: E W Ely; R Margolin; J Francis; L May; B Truman; R Dittus; T Speroff; S Gautam; G R Bernard; S K Inouye Journal: Crit Care Med Date: 2001-07 Impact factor: 7.598
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Pratik P Pandharipande; E Wesley Ely; Rakesh C Arora; Michele C Balas; Malaz A Boustani; Gabriel Heras La Calle; Colm Cunningham; John W Devlin; Julius Elefante; Jin H Han; Alasdair M MacLullich; José R Maldonado; Alessandro Morandi; Dale M Needham; Valerie J Page; Louise Rose; Jorge I F Salluh; Tarek Sharshar; Yahya Shehabi; Yoanna Skrobik; Arjen J C Slooter; Heidi A B Smith Journal: Intensive Care Med Date: 2017-06-13 Impact factor: 17.440
Authors: Mary E Larkin; Catherine C Beauharnais; Kendra Magyar; Laurel Macey; Kerry B Grennan; Emily E Boykin; Steven J Russell Journal: Clin Trials Date: 2012-11-20 Impact factor: 2.486
Authors: Paul A Harris; Robert Taylor; Brenda L Minor; Veida Elliott; Michelle Fernandez; Lindsay O'Neal; Laura McLeod; Giovanni Delacqua; Francesco Delacqua; Jacqueline Kirby; Stephany N Duda Journal: J Biomed Inform Date: 2019-05-09 Impact factor: 6.317
Authors: Joost Witlox; Lisa S M Eurelings; Jos F M de Jonghe; Kees J Kalisvaart; Piet Eikelenboom; Willem A van Gool Journal: JAMA Date: 2010-07-28 Impact factor: 56.272
Authors: E Wesley Ely; Ayumi Shintani; Brenda Truman; Theodore Speroff; Sharon M Gordon; Frank E Harrell; Sharon K Inouye; Gordon R Bernard; Robert S Dittus Journal: JAMA Date: 2004-04-14 Impact factor: 56.272