Search

Beta-blockers are widely used medications for a variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic (e.g., CYP2D6) and pharmacodynamic (e.g., ADRB1, ADRB2, ADRA2C, GRK4, GRK5) genes have been studied in relation to beta-blocker exposure and response. We searched and summarized the strength of the evidence linking beta-blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regarding genetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendations for CYP2D6 and other beta-blockers or for any beta-blocker and the other five genes evaluated (updates at www.cpicpgx.org)., (© 2024 St. Jude Children’s Research Hospital. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone, and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes that have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1, and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone, and methadone, and for OPRM1 and COMT for clinical use., (© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

The Emergency Medicine Specimen Bank (EMSB) was developed to facilitate precision medicine in acute care. The EMSB is a biorepository of clinical health data and biospecimens collected from all adult English- or Spanish-speaking individuals who are able and willing to provide consent and are treated at the UCHealth-University of Colorado Hospital Emergency Department. The EMSB is the first acute care biobank that seeks to enroll all patients, with all conditions who present to the ED. Acute care biobanking presents many challenges that are unique to acute care settings such as providing informed consent in a uniquely stressful and fast-paced environment and collecting, processing, and storing samples for tens of thousands of patients per year. Here, we describe the process by which the EMSB overcame these challenges and was integrated into clinical workflow allowing for operation 24 hours a day, 7 days a week at a reasonable cost. Other institutions can implement this template, further increasing the power of biobanking research to inform treatment strategies and interventions for common and uncommon phenotypes in acute care settings., (© 2018 by the Society for Academic Emergency Medicine.)

For a variety of reasons including cheap computing, widespread adoption of electronic medical records, digitalization of imaging and biosignals, and rapid development of novel technologies, the amount of health care data being collected, recorded, and stored is increasing at an exponential rate. Yet despite these advances, methods for the valid, efficient, and ethical utilization of these data remain underdeveloped. Emergency care research, in particular, poses several unique challenges in this rapidly evolving field. A group of content experts was recently convened to identify research priorities related to barriers to the application of data science to emergency care research. These recommendations included: 1) developing methods for cross-platform identification and linkage of patients; 2) creating central, deidentified, open-access databases; 3) improving methodologies for visualization and analysis of intensively sampled data; 4) developing methods to identify and standardize electronic medical record data quality; 5) improving and utilizing natural language processing; 6) developing and utilizing syndrome or complaint-based based taxonomies of disease; 7) developing practical and ethical framework to leverage electronic systems for controlled trials; 8) exploring technologies to help enable clinical trials in the emergency setting; and 9) training emergency care clinicians in data science and data scientists in emergency care medicine. The background, rationale, and conclusions of these recommendations are included in the present article., (© 2018 by the Society for Academic Emergency Medicine.)

Drug-drug interactions have been demonstrated to alter cytochrome 2D6 (CYP2D6) enzyme phenotype due to inhibitor ingestion, although it is unclear how substrate interactions affect phenotype. This was a pragmatic clinical trial examining the kinetics of a CYP2D6 enzyme probe drug with and without CYP2D6-dependent substrates. Patients were enrolled into an inpatient study unit, and orally administered a 2 mg microdose of dextromethorphan (DM) to probe enzyme activity with and without CYP2D6-dependent drug-drug interactions. Thirty-nine subjects were enrolled in this trial. Twelve subjects were on no CYP2D6-dependent drugs and 27 were on one or more CYP2D6-dependent drugs. There were 1 poor metabolizer, 5 intermediate metabolizers, 31 normal metabolizers, and 2 ultra-rapid metabolizers. Those with co-ingestion of another CYP2D6-dependent drug were 9.49 (95% confidence interval (CI): 1.54-186.41; P = 0.01) times more likely to have genotype-phenotype discordance based upon the 3 hours dextrophan/dextromethorphan (DX/DM) ratio. CYP2D6 substrate co-ingestions can cause genotype-phenotype discordance., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)

Grant writing starts with crafting an effective specific aims page. This page should be a succinct combination of sales pitch and science. The specific aims page demonstrates a problem and a gap in current knowledge and suggests a solution. It proposes aims that work toward a defended solution and reveal the impact of the proposal on the problem, the field, and future research. The language must be efficient and persuasive; the presentation must drive a reviewer to support the proposal. Here we present a recipe for an effective specific aims page., (© 2018 by the Society for Academic Emergency Medicine.)

Background: Cannabis legalization in Colorado resulted in increased cannabis-associated health care utilization. Our objective was to examine cooccurrence of cannabis and mental health diagnostic coding in Colorado emergency department (ED) discharges and replicate the study in a subpopulation of ED visits where cannabis involvement and psychiatric diagnosis were confirmed through medical review., Methods: We collected statewide ED International Classification of Diseases, 9th Revision, Clinical Modification diagnoses from the Colorado Hospital Association and a subpopulation of ED visits from a large, academic hospital from 2012 to 2014. Diagnosis codes identified visits associated with mental health and cannabis. Codes for mental health conditions and cannabis were confirmed by manual records review in the academic hospital subpopulation. Prevalence ratios (PRs) of mental health ED discharges were calculated to compare cannabis-associated visits to those without cannabis. Rates of mental health and cannabis-associated ED discharges were examined over time., Results: Statewide data demonstrated a fivefold higher prevalence of mental health diagnoses in cannabis-associated ED visits (PR = 5.35, 95% confidence interval [CI], 5.27-5.43) compared to visits without cannabis. The hospital subpopulation supported this finding with a fourfold higher prevalence of psychiatric complaints in cannabis attributable ED visits (PR = 4.87, 95% CI = 4.36-5.44) compared to visits not attributable to cannabis. Statewide rates of ED visits associated with both cannabis and mental health significantly increased from 2012 to 2014 from 224.5 to 268.4 per 100,000 (p < 0.0001)., Conclusions: In Colorado, the prevalence of mental health conditions in ED visits with cannabis-associated diagnostic codes is higher than in those without cannabis. There is a need for further research determining if these findings are truly attributed to cannabis or merely coincident with concurrent increased use and availability., (© 2018 by the Society for Academic Emergency Medicine.)

Precision medicine is an emerging approach to disease treatment and prevention that considers variability in patient genes, environment, and lifestyle. However, little has been written about how such research impacts emergency care. Recent advances in analytical techniques have made it possible to characterize patients in a more comprehensive and sophisticated fashion at the molecular level, promising highly individualized diagnosis and treatment. Among these techniques are various systematic molecular phenotyping analyses (e.g., genomics, transcriptomics, proteomics, and metabolomics). Although a number of emergency physicians use such techniques in their research, widespread discussion of these approaches has been lacking in the emergency care literature and many emergency physicians may be unfamiliar with them. In this article, we briefly review the underpinnings of such studies, note how they already impact acute care, discuss areas in which they might soon be applied, and identify challenges in translation to the emergency department (ED). While such techniques hold much promise, it is unclear whether the obstacles to translating their findings to the ED will be overcome in the near future. Such obstacles include validation, cost, turnaround time, user interface, decision support, standardization, and adoption by end-users., Competing Interests: There are no relevant commercial conflicts of interest., (© 2016 by the Society for Academic Emergency Medicine.)

Objectives: Case reports have described a syndrome of cyclic vomiting associated with chronic marijuana use, termed cannabinoid hyperemesis syndrome. The primary objective was to determine the prevalence of patients presenting with cyclic vomiting before and after the liberalization of medical marijuana in Colorado in 2009. The secondary objective was to describe the odds of marijuana use among cyclic vomiting visits in these same time periods., Methods: This was a cross-sectional study of cyclic vomiting visits to the emergency department (ED) before and after marijuana liberalization. ED visits with International Classification of Diseases, ninth revision, coding for cyclic vomiting or that met diagnostic criteria for cyclic vomiting by the Rome III criteria were included., Results: The authors reviewed 2,574 visits and identified 36 patients diagnosed with cyclic vomiting over 128 visits. The prevalence of cyclic vomiting visits increased from 41 per 113,262 ED visits to 87 per 125,095 ED visits after marijuana liberalization, corresponding to a prevalence ratio of 1.92 (95% confidence interval [CI] = 1.33 to 2.79). Patients with cyclic vomiting in the postliberalization period were more likely to have marijuana use documented than patients in the preliberalization period (odds ratio = 3.59, 95% CI = 1.44 to 9.00)., Conclusions: The prevalence of cyclic vomiting presentations nearly doubled after the liberalization of medical marijuana. Patients presenting with cyclic vomiting in the postliberalization period were more likely to endorse marijuana use, although it is unclear whether this was secondary to increased marijuana use, more accurate marijuana reporting, or both., (© 2015 by the Society for Academic Emergency Medicine.)

Objectives: The hepatic cytochrome 2D6 (CYP2D6) is a saturable enzyme responsible for metabolism of approximately 25% of known pharmaceuticals. CYP interactions can alter the efficacy of prescribed medications. Hydrocodone is largely dependent on CYP2D6 metabolism for analgesia, ondansetron is inactivated by CYP2D6, and oxycodone analgesia is largely independent of CYP2D6. The objective was to determine if CYP2D6 medication coingestion decreases the effectiveness of hydrocodone., Methods: This was a prospective observational study conducted in an academic U.S. emergency department (ED). Subjects were included if they had self-reported pain or nausea and were excluded if they were unable to speak English, were less than 18 years of age, had liver or renal failure, or carried diagnoses of chronic pain or cyclic vomiting. Detailed drug ingestion histories for the preceding 48 hours prior to the ED visit were obtained. The patient's pain and nausea were quantified using a 100-mm visual analog scale (VAS) at baseline prior to drug administration and following doses of hydrocodone, oxycodone, or ondansetron. We used a mixed model with random subject effect to determine the interaction between CYP2D6 drug ingestion and study drug effectiveness. Odds ratios (ORs) were calculated to compare clinically significant VAS changes between CYP2D6 users and nonusers., Results: A total of 250 (49.8%) of the 502 subjects enrolled had taken at least one CYP2D6 substrate, inhibitor, or inducing pharmaceutical, supplement, or illicit drug in the 48 hours prior to ED presentation. CYP2D6 drug users were one-third as likely to respond to hydrocodone (OR = 0.33, 95% confidence interval [CI] = 0.1 to 0.8) and more than three times as likely as nonusers to respond to ondansetron (OR = 3.4, 95% CI = 1.3 to 9.1). There was no significant difference in oxycodone effectiveness between CYP2D6 users and nonusers (OR = 0.53, 95% CI = 0.3 to 1.1)., Conclusions: CYP2D6 drug-drug interactions appear to change effectiveness of commonly prescribed drugs in the ED. Drug-drug interaction should be considered prior to prescribing CYP2D6 drugs., (© 2014 by the Society for Academic Emergency Medicine.)

Objectives: The objective was to ascertain whether acetaminophen (APAP) concentrations less than 100 μg/mL obtained between 1 and 4 hours after acute ingestion accurately predict a nontoxic 4-hour concentration., Methods: The authors performed a multicenter, prospective cohort study involving five emergency departments (EDs) participating in the ToxIC Research Network. Data were collected from May 2009 to December 2011. Patients with APAP concentrations <100 μg/mL drawn between 1 and 4 hours after acute ingestions, and concentrations drawn 4 or more hours after ingestions, were included in the study. Exclusion criteria included initial concentration >100 μg/mL, initial APAP concentration drawn prior to 1 hour, two undetectable APAP concentrations, the second concentration drawn prior to 4 hours, and unknown time of ingestion. Toxic concentrations 4 or more hours after ingestion were defined as concentrations that plotted above the 150 μg/mL line on the Rumack-Matthew nomogram., Results: Data were collected on 83 patients who met inclusion criteria. Of the 83 patients with APAP concentrations <100 μg/mL between 1 and 4 hours, one patient (1.2%) had a ≥ 4-hour toxic concentration. Negative predictive value (NPV) for an APAP concentration <100 μg/mL obtained between 1 and 4 hours after an acute ingestion was 98.8% (95% confidence interval [CI] = 93.5% to 99.8%)., Conclusions: An APAP concentration of <100 μg/mL obtained between 1 and 4 hours after ingestion has a high NPV for excluding toxic ingestion. We do not recommend reliance on concentrations obtained between 1 and 4 hours to exclude toxicity, because of a potential false-negative rate of 6.5%., (© 2013 by the Society for Academic Emergency Medicine.)

Background: Very limited data is available regarding the safety of levetiracetam in cases of unintentional or intentional ingestions., Methods: All cases of single agent ingestions of levetiracetam, excluding adverse drug reactions (ADRs), reported to 61 American poison control centers during 2000-2009 were identified. Demographics, dose, symptoms, and medical outcome were abstracted from each case record., Results: A total of 222 cases of single agent levetiracetam ingestions were reported during the study period. Median age was 14.0 years (IQR: 2.0 years, 39.0 years) and 51.8% were female. In 207 of 222 cases (93.2%) medical outcome was known. No deaths were reported and only 1 (0.5%) case resulted in a major outcome and 3 (1.4%) cases resulted in moderate outcomes. Minor, minimal, or no effects were reported in 198 (89.2%) cases. In 27 (12.2%) cases, ingestion was intentional and in 192 (86.5%) unintentional. There were no major outcomes and only one case (1.4%) of moderate outcome in 74 children aged 6 years or less. All ingestions in these children were unintentional., Conclusions: In this study with a limited number of cases, intentional and unintentional ingestions of levetiracetam were safe in the majority of cases., (Copyright © 2011 John Wiley & Sons, Ltd.)