A cross-sectional analysis of fentanyl analog exposures among living patients.

Background: Synthetic opioids, including fentanyl analogs, contribute to an increasing proportion of opioid-related deaths. Highly potent analogs pose an increased risk for fatal overdose. The prevalence of fentanyl analog exposures in patients with known opioid exposure is unknown.Objective: The purpose of this study was to determine the exposure prevalence for fentanyl analogs in living patients with positive urine screens for opiates or fentanyl.Methods: This was a cross-sectional analysis of urine high performance liquid chromatography/tandem mass spectroscopy (HPLC-MS/MS) results from patients with a positive urine screen for opiates or fentanyl at a large public healthcare system in Chicago, Illinois. Samples with positive screens were non-continuously tested by HPLC-MS/MS for 5 selected months in 2018 and 2019.Results: A total of 219 urine samples which screened positive for fentanyl or opiates underwent HPLC-MS/MS testing. At least one fentanyl analog was detected in 65.3% (n = 143) of samples with 26.0% (n = 57) testing positive for multiple analogs. The most common analogs, intermediates, or metabolites were: 4-ANPP (n = 131); 2-furanylfentanyl (n = 22); acryl fentanyl (n = 21); butyrylfentanyl (n = 15); cyclopropylfentanyl (n = 15); and carfentanil (n = 13). Of samples which screened positive for fentanyl (n = 188), 70.2% (132) tested positive for at least one fentanyl analog. Of samples which screened negative for fentanyl but positive for opiates (n = 31), 35.5% (n = 11) tested positive for fentanyl analogsConclusion: Fentanyl analog exposure is common in patients with positive urine screens for fentanyl or opiates. Screening living patient samples for synthetic opioids has future toxicosurveillance implications and these data underscore the increased risks from illicit opioid use.

An outbreak of severe coagulopathy from synthetic cannabinoids tainted with Long-Acting anticoagulant rodenticides.

Objective: To describe a large regional poison center's experience managing an outbreak of long-acting anticoagulant rodenticide (LAAR) poisoning associated with synthetic cannabinoid (SC) use.Methods: This is a retrospective review of exposures reported to the Illinois Poison Center between March 10 and August 1, 2018. All cases coded as exposure to Δ9-tetrahydrocannabinol homologs were identified. Patients with suspected SC use, positive LAAR testing, and coagulopathy (signs or symptoms of bleeding or international normalized ratio [INR] > 2) were included. If confirmatory LAAR testing was performed and resulted as negative, the patient was excluded from this analysis. In the absence of LAAR testing, patients with suspected SC use, an INR >2, and no alternative explanation of coagulopathy were included. Suspected SC use was defined as use suspected by a member of the treating team or reported by the patient. Presenting signs and symptoms, laboratory findings, management, healthcare utilization, outcomes, and disposition of patients affected by this outbreak were reported.Results: One hundred seventy-eight cases met inclusion criteria. Most patients were male (73%) and young to middle-aged (median age 32, IQR 25-40). Most presented to hospitals in Peoria (35%) and Cook (31%) counties. Median hospitalization was three days (IQR 2-4). Eighty-eight percent of patients presented with an INR >10. Eighteen cases had qualitative anticoagulant testing, all of which were positive for brodifacoum. Other identified LAARs included difenacoum (10/18) and bromadiolone (1/18). Sixty-three percent of patients had back, flank or abdominal pain; 70% of patients presented with hematuria. One hundred six cases received IV vitamin K1; no adverse or anaphylactoid reactions were reported. Forty-one (22%) patients left AMA. Thirty-eight patients (21%) were re-hospitalized during the study period. Patients leaving AMA were 1.6 times more likely to be re-hospitalized than patients with other dispositions. Intracranial hemorrhage, present in 3% of total cases, was present in 4 of 5 fatalities.Conclusions: We describe an outbreak of multiple LAARs contaminating SCs. Patients presented with bleeding from varied sites, often required blood products, factor replacement, and high dose vitamin K1 for stabilization.

Role of neuronal activity and kinesin on tract tracing by manganese-enhanced MRI (MEMRI).

MEMRI offers the exciting possibility of tracing neuronal circuits in living animals by MRI. Here we use the power of mouse genetics and the simplicity of the visual system to test rigorously the parameters affecting Mn2+ uptake, transport and trans-synaptic tracing. By measuring electrical response to light before and after injection of Mn2+ into the eye, we determine the dose of Mn2+ with the least toxicity that can still be imaged by MR at 11.7 T. Using mice with genetic retinal blindness, we discover that electrical activity is not necessary for uptake and transport of Mn2+ in the optic nerve but is required for trans-synaptic transmission of this tracer to distal neurons in this pathway. Finally, using a kinesin light chain 1 knockout mouse, we find that conventional kinesin is a participant but not essential to neuronal transport of Mn2+ in the optic tract. This work provides a molecular and physiological framework for interpreting data acquired by MEMRI of circuitry in the brain.