Multiplex SNaPshot-a new simple and efficient CYP2D6 and ADRB1 genotyping method.

BACKGROUND: Reliable, inexpensive, high-throughput genotyping methods are required for clinical trials. Traditional assays require numerous enzyme digestions or are too expensive for large sample volumes. Our objective was to develop an inexpensive, efficient, and reliable assay for CYP2D6 and ADRB1 accounting for numerous polymorphisms including gene duplications. MATERIALS AND METHODS: We utilized the multiplex SNaPshot® custom genotype method to genotype CYP2D6 and ADRB1. We compared the method to reference standards genotyped using the Taqman Copy Number Variant Assay followed by pyrosequencing quantification and determined assigned genotype concordance. RESULTS: We genotyped 119 subjects. Seven (5.9 %) were found to be CYP2D6 poor metabolizers (PMs), 18 (15.1 %) intermediate metabolizers (IMs), 89 (74.8 %) extensive metabolizers (EMs), and 5 (4.2 %) ultra-rapid metabolizers (UMs). We genotyped two variants in the ß1-adrenoreceptor, rs1801253 (Gly389Arg) and rs1801252 (Ser49Gly). The Gly389Arg genotype is Gly/Gly 18 (15.1 %), Gly/Arg 58 (48.7 %), and Arg/Arg 43 (36.1 %). The Ser49Gly genotype is Ser/Ser 82 (68.9 %), Ser/Gly 32 (26.9), and Gly/Gly 5 (4.2 %). The multiplex SNaPshot method was concordant with genotypes in reference samples. CONCLUSIONS: The multiplex SNaPshot method allows for specific and accurate detection of CYP2D6 genotypes and ADRB1 genotypes and haplotypes. This platform is simple and efficient and suited for high throughput.

Gun Access and Safety Practices among Older Adults.

Background. Given high rates of gun ownership among older adults, geriatric providers can assess firearm safety practices using a "5 Ls" approach: Locked; Loaded; Little children; feeling Low; and Learned owner. This study describes gun access and the "5 Ls" among US older adults. Methods. Data on the "5 Ls" from the Second Injury Control and Risk Survey (ICARIS-2), a national telephone survey conducted by the Centers for Disease Control and Prevention, were analyzed. Weighted variables were used to generate national estimates regarding prevalence of gun ownership and associated gun safety among older adults (≥55 years). Results. Of 2939 older adults, 39% (95% CI 37%-42%) reported ≥1 gun stored at home. Among those with guns at home, 21% (95% CI 18-24%) stored guns loaded and unlocked; 9.2% (95% CI 6.6-12%) had ≥1 child in household; 5.1% (95% CI 3.5-6.8%) reported past-year suicidal ideation and 3.6% (95% CI 2.1-5.2%) reported history of a suicide attempt; and 55% (95% CI 51-59%) stated that ≥1 adult had attended firearm safety workshop. Conclusion. Some older adults may be at elevated risk of firearm injury because of storage practices, suicidal thoughts, or limited safety training. Future work should assess effective approaches to reduce the risk of gun-related injuries among older adults.

Driving Rehabilitation Specialists' Perspectives on Older Driver Evaluations.

OBJECTIVE: We explored driving rehabilitation specialists' (DRSs') perspectives on older driver evaluations. METHOD: We conducted interviews with 26 DRSs across the United States who evaluate older drivers. Transcript analysis followed general inductive techniques to identify themes related to current systems and barriers to use. RESULTS: Themes, by Social-Ecological Model level, were as follows: (1) individual occupational therapists' commitment to mobility and safety, perceived responsibilities, and experience; (2) DRSs' relationships with drivers, medical providers, and licensing bureaus; (3) the community surrounding the DRSs, including the health care system and transportation resources; and (4) societal factors, including DRS reimbursement, reporting requirements and liability coverage, and role of national organizations. CONCLUSIONS: This qualitative study identified barriers to the development of an effective system for older driver evaluations. Future work should verify, refine, and expand these findings by targeting other stakeholder groups.

Clinically Inconsequential Alerts: The Characteristics of Opioid Drug Alerts and Their Utility in Preventing Adverse Drug Events in the Emergency Department.

STUDY OBJECTIVE: We examine the characteristics of clinical decision support alerts triggered when opioids are prescribed, including alert type, override rates, adverse drug events associated with opioids, and preventable adverse drug events. METHODS: This was a retrospective chart review study assessing adverse drug event occurrences for emergency department (ED) visits in a large urban academic medical center using a commercial electronic health record system with clinical decision support. Participants include those aged 18 to 89 years who arrived to the ED every fifth day between September 2012 and January 2013. The main outcome was characteristics of opioid drug alerts, including alert type, override rates, opioid-related adverse drug events, and adverse drug event preventability by clinical decision support. RESULTS: Opioid drug alerts were more likely to be overridden than nonopioid alerts (relative risk 1.35; 95% confidence interval [CI] 1.21 to 1.50). Opioid drug-allergy alerts were twice as likely to be overridden (relative risk 2.24; 95% CI 1.74 to 2.89). Opioid duplicate therapy alerts were 1.57 times as likely to be overridden (95% CI 1.30 to 1.89). Fourteen of 4,581 patients experienced an adverse drug event (0.31%; 95% CI 0.15% to 0.47%), and 8 were due to opioids (57.1%). None of the adverse drug events were preventable by clinical decision support. However, 46 alerts were accepted for 38 patients that averted a potential adverse drug event. Overall, 98.9% of opioid alerts did not result in an actual or averted adverse drug event, and 96.3% of opioid alerts were overridden. CONCLUSION: Overridden opioid alerts did not result in adverse drug events. Clinical decision support successfully prevented adverse drug events at the expense of generating a large volume of inconsequential alerts. To prevent 1 adverse drug event, providers dealt with more than 123 unnecessary alerts. It is essential to refine clinical decision support alerting systems to eliminate inconsequential alerts to prevent alert fatigue and maintain patient safety.

CYP2C19 drug-drug and drug-gene interactions in ED patients.

BACKGROUND: CYP450 polymorphisms result in variable rates of drug metabolism. CYP drug-drug interactions can contribute to altered drug effectiveness and safety. STUDY OBJECTIVES: The primary objective was to determine the percentage of emergency department (ED) patients with cytochrome 2C19 (CYP2C19) drug-drug interactions. The secondary objective was to determine the prevalence of CYP2C19 polymorphisms in a US ED population. METHODS: We conducted a prospective observational study in an urban academic ED with 72,000 annual visits. Drug ingestion histories for the 48 hours preceding ED visit were obtained; each drug was coded as CYP2C19 substrate, inhibitor, inducer, or not CYP2C19 dependent. Ten percent of patients were randomized to undergo CYP2C19 genotyping using the Roche Amplichip. RESULTS: A total of 502 patients were included; 61% were female, 65% were white, and median age was 39 years (interquartile range, 22-53). One hundred thirty-one (26.1%) patients had taken at least 1 CYP2C19-dependent home drug. Eighteen (13.7%) patients who were already taking a CYP2C19-dependent drug were given or prescribed a CYP2C19-dependent drug while in the ED. Among the 53 patients genotyped, 52 (98%) were extensive metabolizers and 1 was a poor metabolizer. CONCLUSIONS: In a population of ED patients, more than a quarter had taken a CYP2C19-dependent drug in the preceding 48 hours, but few were given or prescribed another CYP2C19-dependent drug in the ED. On genotyping analysis, CYP2C19 polymorphisms were uncommon in our cohort. We conclude that changing prescribing practice due to CYP2C19 drug-drug interaction or genotype is unlikely to be useful in most US ED populations.

Butane Hash Oil Burns Associated with Marijuana Liberalization in Colorado.

Butane hash oil (BHO), also known as "amber," "dab," "glass," "honey," "shatter," or "wax," is a potent marijuana concentrate, containing up to 90 % tetrahydrocannabinol (THC). BHO is easily manufactured using highly volatile butane as a solvent. Our objective was to characterize hydrocarbon burns associated with BHO manufacture in Colorado. This was a cross-sectional study utilizing the National Burn Repository to capture all hydrocarbon burns reported to the local burn center from January 1st, 2008, through August 31st, 2014. We abstracted demographic and clinical variables from medical records for patients admitted for hydrocarbon burns associated with butane hash oil extraction. Twenty-nine cases of BHO burns were admitted to the local burn center during the study period. Zero cases presented prior to medical liberalization, 19 (61.3 %) during medical liberalization (Oct 2009-Dec 2013), and 12 (38.7 %) in 2014 since legalization. The majority of cases were Caucasian (72.4 %) males (89.7 %). Median age was 26 (range 15-58). The median total-body-surface-area (TBSA) burn size was 10 % (TBSA range 1-90 %). Median length of hospital admission was 10 days. Six required intubation for airway protection (21 %). Nineteen required skin grafting, eight wound care only, one required surgical fracture repair, and one required surgical debridement. Hydrocarbon burns associated with hash oil production have increased since the liberalization of marijuana policy in Colorado. A combination of public health messaging, standardization of manufacturing processes, and worker safety regulations are needed to decrease the risks associated with BHO production.

Captured segment exchange: a strategy for custom engineering large genomic regions in Drosophila melanogaster.

Site-specific recombinases (SSRs) are valuable tools for manipulating genomes. In Drosophila, thousands of transgenic insertions carrying SSR recognition sites have been distributed throughout the genome by several large-scale projects. Here we describe a method with the potential to use these insertions to make custom alterations to the Drosophila genome in vivo. Specifically, by employing recombineering techniques and a dual recombinase-mediated cassette exchange strategy based on the phiC31 integrase and FLP recombinase, we show that a large genomic segment that lies between two SSR recognition-site insertions can be "captured" as a target cassette and exchanged for a sequence that was engineered in bacterial cells. We demonstrate this approach by targeting a 50-kb segment spanning the tsh gene, replacing the existing segment with corresponding recombineered sequences through simple and efficient manipulations. Given the high density of SSR recognition-site insertions in Drosophila, our method affords a straightforward and highly efficient approach to explore gene function in situ for a substantial portion of the Drosophila genome.