Risk of Overdose with Exposure to Prescription Opioids, Benzodiazepines, and Non-benzodiazepine Sedative-Hypnotics in Adults: a Retrospective Cohort Study.

BACKGROUND: Concurrent use of benzodiazepines in opioid users has been linked to a higher risk of an emergency room visit or inpatient admission for opioid overdose and death from drug overdose. Further research is needed to confirm the findings and analyze contributing risk factors for opioid overdoses in a large commercially insured population. OBJECTIVES: To estimate the risk of opioid overdose associated with opioid users exposed to various combinations of opioid, benzodiazepine, and non-benzodiazepine sedative-hypnotic therapy. To identify other factors that are associated with increased risk for opioid overdose. DESIGN: Retrospective cohort study. PATIENTS: New start adult users of opioids, defined as naïve to opioids for 6 months, in Kaiser Permanente California regions from January 2013 through September 2017. MAIN MEASURES: Inpatient or emergency department admissions due to opioid-related overdose. KEY RESULTS: A total of 2,241,530 patients were included in this study. Patients exposed to opioids, benzodiazepines, and non-benzodiazepine sedative-hypnotics at any point during their follow-up were 60% more likely to overdose than those who were only exposed to opioids (p < 0.0001). Those exposed to opioids and benzodiazepines were 20% more likely to have an opioid-related overdose than those exposed to opioids only (p < 0.0001). Significant risk factors for opioid overdose included exposure to all three medication classes, higher opioid dosage strengths, elderly age (age ≥ 65 years), history of previous overdose, and substance use disorder. CONCLUSIONS: Results from this study demonstrate a significant increase in risk of opioid overdose in patients exposed to combinations of sedative-hypnotics with opioids compared to those only taking opioids. Findings from this study provide evidence that opioids should be avoided in combination with benzodiazepines and non-benzodiazepine sedative-hypnotics, used at the lowest dose possible, and used with caution in the elderly, those with previous history of overdose, and those with substance use disorder at baseline.

High genetic variability of norovirus leads to diagnostic test challenges.

BACKGROUND: It is important to understand the diagnostic accuracy of multiplex panels such as the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP) as they are increasingly employed for routine diagnostics worldwide. Recent evaluations in our laboratory identified lower detection rates of norovirus genogroup II (NoV GII) using GPP compared to our laboratory-developed RT-qPCR, Gastroenteritis Virus Panel (GVP). OBJECTIVES: To characterize the cases of discordant NoV GII results between GPP and GVP and determine the sensitivity of the two assays for specific NoV GII genotypes. STUDY DESIGN: We genotyped discordant NoV GII strains identified in stool samples or rectal swabs collected prospectively from a cohort of children with acute gastroenteritis between December 2014 and July 2016. The sensitivities of GVP and GPP for NoV GII were compared by analyses of GVP threshold cycle (Ct) and ten-fold serial dilutions of positive samples of various NoV GII genotypes. RESULTS: All discordant samples (63/607) were NoV GII positive by GVP but negative by GPP. Twenty-two were successfully genotyped, fourteen of which were NoV GII genotype 2 (GII.2). The median Ct value of concordant positives was lower than that of discordant results (19.8 vs. 33.7; P<0.0001). GVP was 10 and at least 10,000-fold more sensitive than GPP in detecting NoV GII.3 and GII.2, respectively, but has similar sensitivity for NoV GII.4. Discordant GII.2 variant differed genetically from concordant GII.2 variants. CONCLUSIONS: GPP has lower sensitivity to detect NoV GII.2 than GVP and its use may lead to undetected cases clinically, and an underestimation of NoV disease burden at the population level.