Analysis of comprehensive pharmacogenomic profiling to impact in-hospital prescribing.

INTRODUCTION: In-hospital adverse medication events result in increased morbidity and mortality. Many implicated drugs carry pharmacogenomic information. We hypothesized that comprehensive pre-emptive pharmacogenomic profiling could have high relevance for in-hospital prescribing. PATIENTS AND METHODS: We retrospectively analyzed the in-hospital medications of a genotyped outpatient cohort admitted at our institution from 2012 to 2015. The endpoints were medication changes (new medications initiated, dose adjustments, or medications discontinued) involving drugs with pharmacogenomic annotations from three sources: Clinical Pharmacogenetics Implementation Consortium guidance, Food and Drug Administration label information, and drugs with clinical decision supports in our institutional pharmacogenomic Genomic Prescribing System. RESULTS: Of 867 genotyped outpatients, 20 were hospitalized (mean: 78.2 years, 65% male). This hospitalized cohort was significantly older (78.2 vs. 61.3 years, P<0.0001) and took more medications (8.9 vs. 5.0 medications, P<0.0001). Out of 159 medication changes made, most (67.9%) were new medications (average: 2.5/hospitalization) with one-third of these having clinically annotated pharmacogenomic information. Half of all hospitalizations involved at least one pharmacogenomic medication. Over half (55%) of the hospitalized cohort was newly prescribed at least one of eight key pharmacogenomic medications, including high-risk drugs such as clopidogrel, codeine, and warfarin. CONCLUSION: Our study suggested that older patients and those with polypharmacy were at increased risk for hospitalizations, where many new prescriptions included frequently used pharmacogenomic drugs. Targeting this group for pre-emptive genotyping would facilitate the delivery of highly relevant information to inform inpatient prescribing.

[Construction of LAMP detection method for poppy codeine in seasoning powders].

OBJECTIVE: To establish the detection method for poppy codeine in seasoning power based on the loop-mediated isothermal amplification of DNA( LAMP). METHODS: Establishment of the LAMP reaction system and detection of 8 commercially seasoning powders by the specificity test, optimum temperature test and sensitivity test of DNA samples of 12 poppies seeds, 11 spices leaves or seeds and 1 corn poppy seeds based on the specific genes sequence of codeine. RESULTS: The DNA samples of the 12 poppies and the corn poppy showed the specific reaction, the optimum temperature was 66 ℃ and the minimum detectable concentration was 9 pg/µL, and the sensitivity was 100 times larger than that of PCR. There was codeine in one of the 8 commercially seasoning powders. CONCLUSION: The LAMP method applies to detect the poppy in seasoning powders with its high sensitivity, strong specificity, easy operation.

Pain management of musculoskeletal injuries in children: current state and future directions.

BACKGROUND: Pain is the most common reason for seeking health care in the Western world and is a contributing factor in up to 80% of all emergency department (ED) visits. In the pediatric emergency setting, musculoskeletal injuries are one of the most common painful presentations. Inadequate pain management during medical care, especially among very young children, can have numerous detrimental effects. No standard of care exists for the management of acute musculoskeletal injury-related pain in children. Within the ED setting, pain from such injuries has been repeatedly shown to be undertreated. OBJECTIVES: Upon completion of this CME article, the reader should be better able to (1) distinguish multiple nonpharmacological techniques for minimizing and treating pain and anxiety in children with musculoskeletal injuries, (2) apply recent medical literature in deciding pharmacological strategies for the treatment of children with musculoskeletal injuries, and (3) interpret the basic principles of pharmacogenomics and how they relate to analgesic efficacy. RESULTS: Pediatric musculoskeletal injuries are both common and painful. There is growing evidence that, in addition to pharmacological therapy, nonpharmacological methods can be introduced to improve analgesia in the ED and after discharge. Traditionally, acetaminophen with codeine has been used to treat moderate orthopedic injury-related pain in children. Other oral opioids (hydrocodone, oxycodone) are gaining popularity, as well. Current data suggest that ibuprofen is at least as effective as acetaminophen-codeine and codeine alone. Medication compliance might be improved if adverse effects were minimized, and ibuprofen has been shown to have a similar or better adverse effect profile than the oral opioids to which it has been compared. Pharmacogenomic data show that nearly 50% of individuals have at least 1 reduced functioning allele resulting in suboptimal conversion of codeine to active analgesic, so it is not surprising that codeine analgesic efficacy is not optimal. At the same time, nonpharmacological therapies are emerging as commonly used treatment options by parents and adjuncts to analgesic medication. The efficacy and role of techniques (massage, music therapy, transcutaneous electrical nerve stimulation), although promising, require further clarification in the treatment of orthopedic injury pain. CONCLUSIONS: There is a need to optimize the measurement, documentation, and treatment of pain in children. There is growing evidence that nonpharmacological methods can be introduced to improve analgesia in the ED, and efforts to help parents implement these methods at home might be advantageous to optimize outpatient treatment plans. In pharmacotherapy, ibuprofen has emerged as an appropriate first-line choice for mild-moderate orthopedic pain. Other oral opioids (hydrocodone, oxycodone) are gaining popularity over codeine, because of the current understanding of the pharmacogenomics of such medications.

Risk of overdose and death following codeine prescription among immigrants.

BACKGROUND: Immigrants may be at a higher risk of adverse drug reactions, in that poor language proficiency reduces individuals understanding of drug label instructions. Additionally, there are reports of severe or fatal toxicity due to CYP2D6 ultrarapid hepatic metabolism of codeine to morphine among some ethnic groups, especially those from Eastern Africa. METHODS: Between 2002 and 2012 we conducted a population-based cohort study among residents of Ontario, Canada. We used administrative health databases that linked immigrants and Canadian-born individuals to both prescription medication use and emergency department visits and hospital admissions. The primary composite outcome was the risk of drug overdose or all-cause mortality within 30 days of codeine prescription, comparing patients from various world regions to Canadian-born individuals. A secondary analysis stratified by codeine dose and ability to speak English and/or French. RESULTS: There were 553 504 individuals exclusively prescribed codeine. Relative to an incidence rate of 57.1/100 000 person-days among Canadian-born codeine recipients, those who migrated from various world regions were at a lower risk of drug overdose or death. For example, Eastern Africans had an adjusted HR of 0.60 (95% CI 0.31 to 1.17) on controlling for potential confounders such as age, sex, income and physician visits. Patients unable to speak English or French who were prescribed codeine were at a lower risk of the composite outcome relative to those proficient in either language (adjusted HR 0.63, 95% CI 0.54 to 0.74). INTERPRETATION: Overdose and death following the institution of codeine therapy are not more commonly observed among immigrants from world regions with a high prevalence of ultrarapid CYP2D6 status relative to those born in Canada. Lower proficiency in English or French also did not appear to heighten the risk.

Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability.

BACKGROUND: Codeine analgesia is wholly or mostly due to its metabolism to morphine by the cytochrome P450 enzyme CYP2D6, which shows significant genetic variation in activity. The aims of this study were to investigate genotype, phenotype and morphine production from codeine in children undergoing adenotonsillectomy, and to compare analgesia from codeine or morphine combined with diclofenac. METHODS: Ninety-six children received either codeine 1.5 mg kg(-1) or morphine 0.15 mg kg(-1) in a randomized, double-blind design. Genetic analysis was performed and plasma morphine concentrations at 1 h were determined. Postoperative analgesia and side-effects were recorded. RESULTS: Forty-seven per cent of children had genotypes associated with reduced enzyme activity. Mean (SD) morphine concentrations were significantly lower (P<0.001) after codeine [4.5 (0.3) ng ml(-1)] than after morphine [24.7 (1.5) ng ml(-1)], and morphine and its metabolites were not detected in 36% of children given codeine. There was a significant relationship between phenotype and plasma morphine (P=0.02). More children required rescue analgesia after codeine at both 2 (P<0.05) and 4 h after administration (P<0.01). Fifty-six per cent of children vomited after morphine and 29% after codeine (P<0.01). Neither phenotype nor morphine concentration was correlated with either pain score or the need for rescue analgesia (r=-0.21, 95% confidence interval -0.4, -0.01). CONCLUSIONS: Reduced ability for codeine metabolism may be more common than previously reported. Plasma morphine concentration 1 h after codeine is very low, and related to phenotype. Codeine analgesia is less reliable than morphine, but was not well correlated with either phenotype or plasma morphine in this study.