Dataset Information

Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?-Results from the ADRED Study.

ABSTRACT: Individual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and adverse drug reactions (ADR) that lead to admissions to the emergency department (ED). ADR cases of the prospective multi-center observational trial in EDs (ADRED study) were analyzed (n = 776) together with the relevant PGx phenotypes of the enzymes CYP2D6, CYP2C19, CYP2C9, and VKORC1. Overall, the allele frequency distribution in this cohort did not differ from the population frequencies. We compared the frequencies of phenotypes in the subgroups with the drugs suspected of certain ADR, in the remaining cases. The frequency distribution of CYP2C19 differed for the ADR bleeding cases suspected of clopidogrel (p = 0.020). In a logistic regression analysis, higher CYP2C19 activity (OR (95% CI): 4.97 (1.73-14.27)), together with age (1.05 (1.02-1.08)), showed an impact on the clopidogrel-suspecting ADRs, when adjusting for the clinical parameters. There was a trend for an association of phenprocoumon-risk profiles (low VKORC1 or CYP2C9 activity) with phenprocoumon-suspecting ADRs (p = 0.052). The PGx impact on serious ADRs might be highest in drugs that cannot be easily monitored or those that do not provoke mild ADR symptoms very quickly. Therefore, patients that require the intake of those drugs with PGx variability such as clopidogrel, might benefit from PGx testing.

SUBMITTER: Just KS

PROVIDER: S-EPMC7355597 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?-Results from the ADRED Study.

Just Katja S KS Dormann Harald H Schurig Marlen M Böhme Miriam M Fracowiak Jochen J Steffens Michael M Scholl Catharina C Seufferlein Thomas T Gräff Ingo I Schwab Matthias M Stingl Julia C JC

Journal of clinical medicine 20200609 6

Individual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and adverse drug reactions (ADR) that lead to admissions to the emergency department (ED). ADR cases of the prospective multi-center observational trial in EDs (ADRED study) were analyzed (<i>n</i> = 776) together with the relevant PGx phenotypes of the enzymes CYP2D6, CYP2C19, CYP2C9, and VKORC1. Overall, the allele frequency distributio ...[more]

PMID: 32527038

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Project description:BackgroundAlcohol consumption may interfere with absorption, distribution, metabolism, and excretion of medications and increase risk of adverse drug reactions (ADR). Studies report increasing prescription medication use over time, with many U.S. drinkers using alcohol-interactive medication. This study identified trends in incidence of U.S. emergency department (ED) visits for ADR with alcohol involvement (ADR-A), compared characteristics and disposition between ADR-A visits and ADR visits without alcohol involvement (ADR-NA), and examined frequency of implicated medications in such visits for 2005 to 2011.MethodsADR visits were identified through the Drug Abuse Warning Network, a national surveillance system monitoring drug-related ED visits. Analysis accounted for sampling design effects and sampling weights. Estimates are presented for totals (ages 12+), age group, and/or sex. Trends were assessed by joinpoint log-linear regression. Differences between ADR-A and ADR-NA visits were compared using two-tailed Rao-Scott chi-square tests.ResultsFrom 2005 to 2011, incidence of ADR-A visits increased for males and females ages 21 to 34 and females ages 55+. An average of 25,303 ADR-A visits ages 12+ occurred annually. Compared with ADR-NA visits, ADR-A visits were more likely to involve males, patients ages 21 to 54, and 2+ implicated drugs. Alcohol involvement increased odds of more serious outcomes from ADR visits. Central nervous system (CNS) agents were the most common medications in ADR-A visits (59.1%), with nearly half being analgesics (mainly opioid). About 13.8% of ADR-A visits involved psychotherapeutic agents, including antidepressants. Besides CNS and psychotherapeutic agents, ADR-A visits involved a higher percentage of genitourinary-tract agents (mainly for impotence) than ADR-NA visits. Sex and age variations were observed with certain implicated medications.ConclusionsED visits for alcohol-drug interactions can be prevented by avoiding alcohol when taking alcohol-interactive medications. Our results underscore the need for healthcare professionals to routinely ask patients about alcohol consumption and warn of ADR risks before prescribing and dispensing alcohol-interactive medications.

Project description:Fifty years ago, Richard Lewontin found that the vast majority of human genetic variation falls within (~85%) rather than between (~15%) racial groups. This result has been replicated numerous times since and is widely taken to support the notion that genetic differences between racial groups are trivial and thus irrelevant for clinical decision-making. The aim of this study was to consider how the apportionment of pharmacogenomic variation within and between racial and ethnic groups relates to risk disparities for adverse drug reactions. We confirmed that the majority of pharmacogenomic variation falls within (97.3%) rather than between (2.78%) the three largest racial and ethnic groups in the United States: Black, Hispanic, and White. Nevertheless, pharmacogenomic variants showing far greater within than between-group variation can have high predictive value for adverse drug reactions, particularly for minority racial and ethnic groups. We predicted excess adverse drug reactions for minority Black and Hispanic groups, compared to the majority White group, and considered these results in light of the apportionment of genetic variation within and between groups. For 85% within and 15% between group variation, there are 700 excess adverse drug reactions per 1,000 patients predicted for a recessive effect model and 300 for a dominant model. We found high numbers of predicted Black and Hispanic excess adverse drug reactions for widely prescribed platinum chemotherapy compounds, such as cisplatin and oxaliplatin, as well as controlled narcotics, including fentanyl and tramadol. Our results indicate that race and ethnicity, while imprecise proxies for genetic diversity, correlate with patterns of pharmacogenomic variation in a way that is clearly relevant to medical treatment decisions. The effects of this variation is particularly pronounced for Black and Hispanic minority groups, owing to genetic differences from the majority White group. Treatment decisions that are made based on (assumed) White pharmacogenomic variant frequencies can be harmful for minority groups. Ignoring clinically relevant genetic differences among racial and ethnic groups, however well-intentioned, will exacerbate rather than ameliorate health disparities.

Project description:Importance:The Patient Protection and Affordable Care Act of 2010 brought attention to adverse drug events in national patient safety efforts. Updated, detailed, nationally representative data describing adverse drug events can help focus these efforts. Objective:To describe the characteristics of emergency department (ED) visits for adverse drug events in the United States in 2013-2014 and describe changes in ED visits for adverse drug events since 2005-2006. Design, Setting, and Participants:Active, nationally representative, public health surveillance in 58 EDs located in the United States and participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project. Exposures:Drugs implicated in ED visits. Main Outcomes and Measures:National weighted estimates of ED visits and subsequent hospitalizations for adverse drug events. Results:Based on data from 42?585 cases, an estimated 4.0 (95% CI, 3.1-5.0) ED visits for adverse drug events occurred per 1000 individuals annually in 2013 and 2014 and 27.3% (95% CI, 22.2%-32.4%) of ED visits for adverse drug events resulted in hospitalization. An estimated 34.5% (95% CI, 30.3%-38.8%) of ED visits for adverse drug events occurred among adults aged 65 years or older in 2013-2014 compared with an estimated 25.6% (95% CI, 21.1%-30.0%) in 2005-2006; older adults experienced the highest hospitalization rates (43.6%; 95% CI, 36.6%-50.5%). Anticoagulants, antibiotics, and diabetes agents were implicated in an estimated 46.9% (95% CI, 44.2%-49.7%) of ED visits for adverse drug events, which included clinically significant adverse events, such as hemorrhage (anticoagulants), moderate to severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe neurological effects (diabetes agents). Since 2005-2006, the proportions of ED visits for adverse drug events from anticoagulants and diabetes agents have increased, whereas the proportion from antibiotics has decreased. Among children aged 5 years or younger, antibiotics were the most common drug class implicated (56.4%; 95% CI, 51.8%-61.0%). Among children and adolescents aged 6 to 19 years, antibiotics also were the most common drug class implicated (31.8%; 95% CI, 28.7%-34.9%) in ED visits for adverse drug events, followed by antipsychotics (4.5%; 95% CI, 3.3%-5.6%). Among older adults (aged ?65 years), 3 drug classes (anticoagulants, diabetes agents, and opioid analgesics) were implicated in an estimated 59.9% (95% CI, 56.8%-62.9%) of ED visits for adverse drug events; 4 anticoagulants (warfarin, rivaroxaban, dabigatran, and enoxaparin) and 5 diabetes agents (insulin and 4 oral agents) were among the 15 most common drugs implicated. Medications to always avoid in older adults according to Beers criteria were implicated in 1.8% (95% CI, 1.5%-2.1%) of ED visits for adverse drug events. Conclusions and Relevance:The prevalence of emergency department visits for adverse drug events in the United States was estimated to be 4 per 1000 individuals in 2013 and 2014. The most common drug classes implicated were anticoagulants, antibiotics, diabetes agents, and opioid analgesics.

Dataset Information

Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?-Results from the ADRED Study.

Publications

Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?-Results from the ADRED Study.

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