Profound Hyperthermia Associated With Fentanyl and Cocaine Use With Suspected Synephrine Adulteration.

BACKGROUND: Although hyperthermia is described after cocaine intoxication, the two hyperthermic cases discussed were unusual in severity and duration for cocaine alone. Synephrine was found in biological samples of these patients in high concentrations and was suspected to be an adulterant in illicitly obtained drugs. CASE REPORT: Two patients presented to a tertiary care university hospital within 2 days of each other after recreational drug use with delayed and protracted hyperthermia. Synephrine was later found in high concentrations in biological samples as an unexpected drug adulterant. The first patient's presentation came with delayed recognition of hyperthermia and implementation of aggressive cooling measures; he entered multisystem organ failure with prolonged intensive care unit stay and significant morbidity. The second patient's hyperthermia was recognized promptly, and she received early, aggressive cooling, including deep sedation and ice water submersion. She left against medical advice from the hospital at her baseline 3 days after presentation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Synephrine is a suspected adulterant that may be associated with profound hyperthermia. Early recognition of drug overdose and working knowledge of common adulterants can facilitate early targeted management, such as aggressive cooling measures, which may prevent morbidity and mortality.

Organophosphate and Organohalogen Flame-Retardant Exposure and Thyroid Hormone Disruption in a Cross-Sectional Study of Female Firefighters and Office Workers from San Francisco.

Occupational exposures to flame retardants (FRs), a class of suspected endocrine-disrupting compounds, are of health concern for firefighters. We sought to characterize exposure to FR compounds and evaluate their association with thyroid hormone levels, a biomarker of early effect, in female firefighters and office workers in San Francisco. In a cross-sectional study, we measured replacement organophosphate and organohalogen FRs in spot urine samples from firefighters (N = 86) and office workers (N = 84), as well as total thyroxine (T4) and thyroid-stimulating hormone in plasma for 84 firefighters and 81 office workers. Median bis(1,3-dichloro-2-propyl)phosphate (BDCPP) levels were 5 times higher in firefighters than office workers. Among firefighters, a doubling of BDCPP was associated with a 2.88% decrease (95% confidence interval -5.28, -0.42) in T4. We did not observe significant associations between FRs and T4 among office workers. In the full group, intermediate body mass index and a college education were associated with higher FR levels. The inverse association observed between FRs and T4 coupled with the lack of studies on women workers and evidence of adverse health effects from FR exposure─including endocrine disruption and breast cancer risk─warrant further research on occupational exposures and identification of opportunities for exposure reduction.

Glyphosate exposure in early pregnancy and reduced fetal growth: a prospective observational study of high-risk pregnancies.

BACKGROUND: Prenatal glyphosate (GLY) exposure is associated with adverse reproductive outcomes in animal studies. Little is known about the effects of GLY exposure during pregnancy in the human population. This study aims to establish baseline urine GLY levels in a high-risk and racially diverse pregnancy cohort and to assess the relationship between prenatal GLY exposure and fetal development and birth outcomes. METHODS: Random first trimester urine specimens were collected from high risk pregnant women between 2013 and 2016 as part of the Indiana Pregnancy Environmental Exposures Study (PEES). Demographic and clinical data were abstracted from mother and infant medical records. Urine glyphosate levels were measured as a proxy for GLY exposure and quantified using liquid chromatography-tandem mass spectrometry. Primary outcome variables included gestation-adjusted birth weight percentile (BWT%ile) and neonatal intensive care unit (NICU) admission. Relationships between primary outcome variables and GLY exposure were assessed using univariate and multivariate linear and logistic regression models. RESULTS: Urine GLY levels above the limit of detection (0.1 ng/mL) were found in 186 of 187 (99%) pregnant women. Further analyses were limited to 155 pregnant women with singleton live births. The mean age of participants was 29 years, and the majority were non-Hispanic white (70%) or non-Hispanic Black (21%). The mean (± SD) urine GLY level was 3.33 ± 1.67 ng/mL. Newborn BWT%iles were negatively related to GLY (adjusted slope ± SE = -0.032 + 0.014, p = 0.023). Infants born to women living outside of Indiana's large central metropolitan area were more likely to have a lower BWT%ile associated with mother's first trimester GLY levels (slope ± SE = -0.064 ± 0.024, p = 0.007). The adjusted odds ratio for NICU admission and maternal GLY levels was 1.16 (95% CI: 0.90, 1.67, p = 0.233). CONCLUSION: GLY was found in 99% of pregnant women in this Midwestern cohort. Higher maternal GLY levels in the first trimester were associated with lower BWT%iles and higher NICU admission risk. The results warrant further investigation on the effects of GLY exposure in human pregnancies in larger population studies.

A combined assay for quantifying remdesivir and its metabolite, along with dexamethasone, in serum.

BACKGROUND: As global confirmed cases and deaths from coronavirus disease 2019 (COVID-19) surpass 100 and 2.2 million, respectively, quantifying the effects of the widespread treatment of remdesivir (GS-5734, Veklury) and the steroid dexamethasone is becoming increasingly important. Limited pharmacokinetic studies indicate that remdesivir concentrations in serum decrease quickly after dosing, so its primary serum metabolite GS-441524 may have more analytical utility. OBJECTIVES: We developed and validated a method to quantify remdesivir, its metabolite GS-441524 and dexamethasone in human serum. METHODS: We used LC-MS/MS and applied the method to 23 serum samples from seven patients with severe COVID-19. RESULTS: The method has limits of detection of 0.0375 ng/mL for remdesivir, 0.375 ng/mL for GS-441524 and 3.75 ng/mL for dexamethasone. We found low intra-patient variability, but significant inter-patient variability, in remdesivir, GS-441524 and dexamethasone levels. CONCLUSIONS: The significant inter-patient variability highlights the importance of therapeutic drug monitoring of COVID-19 patients and possible dose adjustment to achieve efficacy.

Diagnostic accuracy of a liquid chromatography-tandem mass spectrometry assay in small hair samples for rifampin-resistant tuberculosis drug concentrations in a routine care setting.

BACKGROUND: Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. METHODS: Small hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort) in Uganda. RESULTS: Among the 57 DR-TB patients (58% with pre-XDR/XDR-TB; 70% HIV-positive) contributing analyzable hair samples, the sensitivity of the investigational assay was 94% or higher for all drugs except ethionamide (58.5, 95% confidence interval [CI], 40.7-99.9). Assay specificity was low across all tested analytes within the DR-TB cohort; conversely, assay specificity was 100% for all drugs in the HIV/LTBI cohort. CONCLUSIONS: Hair drug concentrations reflect long-term exposure, and multiple successive regimens commonly employed in DR-TB treatment may result in apparent false-positive qualitative and falsely elevated quantitative hair drug levels when prior treatment histories within the hair growth window are not known.

Associations between polyfluoroalkyl substance and organophosphate flame retardant exposures and telomere length in a cohort of women firefighters and office workers in San Francisco.

BACKGROUND: Environmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential biomarker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA. METHODS: We measured serum concentrations of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters (N = 84) and office workers (N = 79) who participated in the 2014-15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length. RESULTS: Regression results revealed significant positive associations between perfluorooctanoic acid (PFOA) and telomere length and perfluorooctanesulfonic acid (PFOS) and telomere length among the whole cohort. Models stratified by occupation showed stronger and more significant associations among firefighters as compared to office workers. Among firefighters in models adjusted for age, we found positive associations between telomere length and log-transformed PFOA (ß (95%CI) = 0.57(0.12, 1.02)), PFOS (0.44 (0.05, 0.83)), and perfluorodecanoic acid (PFDA) (0.43 (0.02, 0.84)). Modeling PFAS as categories of exposure showed significant associations between perfluorononanoic acid (PFNA) and telomere length among firefighters. Significant associations between OPFR metabolites and telomere length were seen for bis (1,3-dichloro-2-propyl) phosphate (BDCPP) and telomere length among office workers (0.21(0.03, 0.40)) and bis (2-chloroethyl) phosphate (BCEP) and telomere length among firefighters (- 0.14(- 0.28, - 0.01)). For OPFRs, the difference in the direction of effect by occupational group may be due to the disparate detection frequencies and concentrations of exposure between the two groups and/or potential unmeasured confounding. CONCLUSION: Our findings suggest positive associations between PFAS and telomere length in women workers, with larger effects seen among firefighters as compared to office workers. The OPFR metabolites BDCPP and BCEP are also associated with telomere length in firefighters and office workers. Associations between chemical exposures and telomere length reported here and by others suggest mechanisms by which these chemicals may affect carcinogenesis and other adverse health outcomes.

"Zombie" Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York.

BACKGROUND: New psychoactive substances constitute a growing and dynamic class of abused drugs in the United States. On July 12, 2016, a synthetic cannabinoid caused mass intoxication of 33 persons in one New York City neighborhood, in an event described in the popular press as a "zombie" outbreak because of the appearance of the intoxicated persons. METHODS: We obtained and tested serum, whole blood, and urine samples from 8 patients among the 18 who were transported to local hospitals; we also tested a sample of the herbal "incense" product "AK-47 24 Karat Gold," which was implicated in the outbreak. Samples were analyzed by means of liquid chromatography-quadrupole time-of-flight mass spectrometry. RESULTS: The synthetic cannabinoid methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA, also known as MMB-FUBINACA or FUB-AMB) was identified in AK-47 24 Karat Gold at a mean (±SD) concentration of 16.0±3.9 mg per gram. The de-esterified acid metabolite was found in the serum or whole blood of all eight patients, with concentrations ranging from 77 to 636 ng per milliliter. CONCLUSIONS: The potency of the synthetic cannabinoid identified in these analyses is consistent with strong depressant effects that account for the "zombielike" behavior reported in this mass intoxication. AMB-FUBINACA is an example of the emerging class of "ultrapotent" synthetic cannabinoids and poses a public health concern. Collaboration among clinical laboratory staff, health professionals, and law enforcement agencies facilitated the timely identification of the compound and allowed health authorities to take appropriate action.

Association of differential symptoms of stress to hair cortisol and cortisone concentrations among pregnant women in Kenya.

Objectives: The purpose of this study was to characterize the stress experienced by pregnant women in Kenya and assess the relationship between perceived stress and stress-related biomarkers of cortisol and cortisone.Background: Kenyan women are exposed to multiple stressors that may result in chronic stress. However, antenatal stress has not been examined and characterized in Kenya; nor has the relationship between pregnant women's self-reported stress and stress biomarkers been established.Methods: One hundred and fifty women were recruited between 22 and 28 weeks gestation. Participants completed the Perceived Stress Scale (PSS) and a sociodemographic questionnaire. Hair samples were obtained for analysis of cortisol and cortisone. Factor analysis was used to extract unique clusters of stress symptoms from items in the PSS. Regression models were computed to examine relationships of stress to cortisone and cortisol, controlling for obstetric risk.Results: Mean age of the women was 25 years (SD = 5, ±16-41). Their degree of perceived stress and cortisol/cortisone concentrations both indicated moderate levels of stress. There was no association between general perceived stress and either hair cortisol or cortisone. However, factor analysis of the PSS identified three clusters of stress symptoms and one cluster - a woman's negative frame of mind regarding life and inefficacy in handling its problems - was associated with higher levels of cortisone (ß= -.231, p = 0.011).Conclusions: Specific stress symptoms may have unique relationships to specific biomarkers and be more useful in assessment than general perceived stress. Assays of both hair cortisol and cortisone might enable a more comprehensive assessment of glucocorticoid activity and better prediction of health risks from stress.Lay summaryUnderstanding stress among rural pregnant Kenyan women may help in addressing risks during pregnancy that lead to adverse birth outcomes. Findings suggest that a woman's tendency to think negatively about life and to doubt her ability to handle life's problems are symptoms of stress that may contribute to higher levels of stress hormones. Assessing women's specific symptoms of stress and different stress hormones during pregnancy may more effectively identify women who need intervention to reduce their health risk.

Exposure to Perfluoroalkyl Substances in a Cohort of Women Firefighters and Office Workers in San Francisco.

Studies of firefighters have shown increased exposures to carcinogenic compounds and elevated rates of certain cancers compared to the general population, yet this research has focused almost exclusively on men. To address this gap, the Women Firefighters Biomonitoring Collaborative created a biological sample archive and analyzed levels of perfluoroalkyl substances (PFAS) among women firefighters (N = 86) and office workers (N = 84) in San Francisco. Serum samples were collected and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure and compare PFAS levels between firefighters and office workers. 7 of 12 PFAS congeners were detected in the least 70% of the study population, and 4 congeners were detected in 100% of participants. In regression models comparing PFAS levels by occupation and adjusting for potential confounders, firefighters had higher geometric mean concentrations of PFAS compared to office workers PFHxS (2.22 (95% CI = 1.55, 3.18)), PFUnDA (1.83 (95% CI = 0.97, 3.45)), and PFNA (1.26 (95% CI = 1.01, 1.58)). Among firefighters, occupational position predicted exposure-firefighters and officers had higher PFNA, PFOA, PFDA, and PFUnDA levels compared to drivers. Women firefighters are exposed to higher levels of some PFAS compared to office workers, suggesting that some of these exposures may be occupationally related.

Integrating Exposure Knowledge and Serum Suspect Screening as a New Approach to Biomonitoring: An Application in Firefighters and Office Workers.

Firefighters (FF) are exposed to recognized and probable carcinogens, yet there are few studies of chemical exposures and associated health concerns in women FFs, such as breast cancer. Biomonitoring often requires a priori selection of compounds to be measured, and so, it may not detect relevant, lesser known, exposures. The Women FFs Biomonitoring Collaborative (WFBC) created a biological sample archive and conducted a general suspect screen (GSS) to address this data gap. Using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, we sought to identify candidate chemicals of interest in serum samples from 83 women FFs and 79 women office workers (OW) in San Francisco. We identified chemical peaks by matching accurate mass from serum samples against a custom chemical database of 722 slightly polar phenolic and acidic compounds, including many of relevance to firefighting or breast cancer etiology. We then selected tentatively identified chemicals for confirmation based on the following criteria: (1) detection frequency or peak area differences between OW and FF; (2) evidence of mammary carcinogenicity, estrogenicity, or genotoxicity; and (3) not currently measured in large biomonitoring studies. We detected 620 chemicals that matched 300 molecular formulas in the WFBC database, including phthalate metabolites, phosphate flame-retardant metabolites, phenols, pesticides, nitro and nitroso compounds, and per- and polyfluoroalkyl substances. Of the 20 suspect chemicals selected for validation, 8 were confirmed-including two alkylphenols, ethyl paraben, BPF, PFOSAA, benzophenone-3, benzyl p-hydroxybenzoate, and triphenyl phosphate-by running a matrix spike of the reference standards and using m/z, retention time, and the confirmation of at least two fragment ions as criteria for matching. GSS provides a powerful high-throughput approach to identify and prioritize novel chemicals for biomonitoring and health studies.

Organic diet intervention significantly reduces urinary pesticide levels in U.S. children and adults.

BACKGROUND: Previous diet intervention studies indicate that an organic diet can reduce urinary pesticide metabolite excretion; however, they have largely focused on organophosphate (OP) pesticides. Knowledge gaps exist regarding the impact of an organic diet on exposure to other pesticides, including pyrethroids and neonicotinoids, which are increasing in use in the United States and globally. OBJECTIVE: To investigate the impact of an organic diet intervention on levels of insecticides, herbicides, and fungicides or their metabolites in urine collected from adults and children. METHODS: We collected urine samples from four racially and geographically diverse families in the United States before and after an organic diet intervention (n = 16 participants and a total of 158 urine samples). RESULTS: We observed significant reductions in urinary levels of thirteen pesticide metabolites and parent compounds representing OP, neonicotinoid, and pyrethroid insecticides and the herbicide 2,4-D following the introduction of an organic diet. The greatest reductions were observed for clothianidin (- 82.7%; 95% confidence interval [95% CI]: - 86.6%, - 77.6%; p < 0.01), malathion dicarboxylic acid (MDA), a metabolite of malathion (- 95.0%; 95% CI: - 97.0%, - 91.8%; p < 0.01), and 3,5,6-trichlor-2-pyridinol (TCPy), a metabolite of chlorpyrifos (- 60.7%; 95% CI: - 69.6%, - 49.2%; p < 0.01). Metabolites or parent compounds of the fungicides boscalid, iprodione, and thiabendazole and the neonicotinoid insecticide imidacloprid were not detected among participants in our study. CONCLUSION: An organic diet was associated with significant reductions in urinary excretion of several pesticide metabolites and parent compounds. This study adds to a growing body of literature indicating that an organic diet may reduce exposure to a range of pesticides in children and adults. Additional research is needed to evaluate dietary exposure to neonicotinoids, which are now the most widely used class of insecticides in the world.

Stimulant drugs are associated with violent and penetrating trauma.

BACKGROUND: Substance abuse is associated with traumatic injuries. Prior studies of drug use and injury have relied on urine drug of abuse screens, which have false positives, false negatives and inability to detect novel drugs. Our study characterizes the relationship between injury mechanism and drugs of abuse detected in serum via confirmatory testing. METHODS: This prospective observational study was conducted from Jan-Sept 2012 at a level 1 trauma center on trauma patients > 13 years who had blood drawn for routine tests. Demographic, injury and standard laboratory data were abstracted from patient charts. Comprehensive serum drug testing was done using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS, LC1200-TOF/MS 6230, Agilent, Santa Clara, CA). RESULTS: Of 272 patients, 71.0% were male, 30.5% had violent injury type and 32.4% had a penetrating injury mechanism. Violent injury type and penetrating injury mechanisms were more frequent in patients who were male, younger age, Black, or Hispanic (p < 0.05 for all). LC-TOF/MS showed that 46.0% were positive for at least one drug. Stimulant drugs were associated with violent injury type (OR 2.9; 95% CI 1.64-5.15) and penetrating injury mechanism (OR 3.3; 95% CI 1.86-5.82). Tobacco use was associated with violent injury type (OR 3.9; 95% CI 2.25-6.77) and penetrating injury mechanism (OR 4.14; 95%CI 2.4-7.14). CONCLUSIONS: Many drugs are present in trauma patients that are not routinely detected on urine drug of abuse tests. Both stimulant drugs and cigarette smoking are indicators of multidimensional hazardous behaviors, which were associated with more violent and penetrating trauma.

Ibogaine Consumption With Seizure-Like Episodes, QTc-Prolongation, and Captured Cardiac Dysrhythmias.

BACKGROUND: Ibogaine is a psychoactive indole alkaloid that has been investigated for use as a treatment for opioid addiction. While not commercially available in the United States, it is available via Internet suppliers. Ibogaine use has been associated with significant cardiac and neurologic effects, such as QT-segment prolongation, cardiac dysrhythmias, hallucinations, seizures, and central nervous system depression. We present a case of verified ibogaine exposure with associated QTc prolongation and torsade de pointes with qualitative analysis of the ingested substance, and examine the history, social context, availability, and perceptions of ibogaine's effects and safety. CASE REPORT: A 34-year-old white woman with medical history significant for heroin and cocaine use disorder presented with reported seizures 1 day after ingestion of 2 g ibogaine powder purchased from an Internet supplier. Shortly after ingestion, she experienced hallucinations and was reported by family to have four to five seizure-like episodes, at one point becoming apneic. In the emergency department, she was noted to have QTc prolongation and several episodes of torsade de pointes. Qualitative analysis confirmed the presence of ibogaine in the empty foil packages containing the ingested substance. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As increasing numbers of opioid-dependent patients attempt to curtail their substance use disorders, we anticipate a rise in ibogaine exposures, necessitating awareness by front-line clinicians in recognizing and treating a drug exposure that can rapidly become life-threatening.

Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial.

BACKGROUND: Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis. METHODS: We did this single-centre, 150-day, double-blind, randomised, placebo-controlled, crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients who fulfilled international panel criteria for diagnosis with disease duration of less than 15 years were eligible. Patients were randomly assigned (1:1) via block randomisation using a random number generator to receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for 60 days (group 2). The primary outcome was shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked potentials. We analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02040298. FINDINGS: Between Jan 1, 2014, and April 11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25). All patients completed the study. The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5-2·9; p=0·0048) when analysing the trial as a crossover. Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported. INTERPRETATION: To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage. FUNDING: University of California, San Francisco and the Rachleff Family.

Seizures, Systemic Inflammatory Response, and Rhabdomyolysis Associated With Laboratory-Confirmed 2C-I and 25-I Exposure.

The 2C drugs are hallucinogenic phenethylamines. They and their n-benzyloxymethyl analogs have become popular as "legal highs," and significant toxicity has been attributed to their use. We report on a case of seizures, systemic inflammatory response, and rhabdomyolysis associated with laboratory-confirmed 4-iodo-2,5-dimethoxyphenethylamine and 4-iodo-2,5-dimethoxy-N-(2-methoxybenzyl) phenethylamine exposure. A 17-year-old male teenager developed seizures after taking "2 strips of acid." The seizures resolved with midazolam, but he became apneic and was intubated. His head computed tomography was unremarkable. Initial creatinine level was 1.5 mg/dL, with a creatine kinase of 112 U/L. His urine immunoassay drug screen was negative. He was extubated within 12 hours but had elevated temperatures for 48 hours. He was treated with antibiotics, but no source of infection was identified. His creatinine level peaked at 2.46 mg/dL. His creatine kinase peaked 72 hours later at 14579 U/L. He was treated with intravenous fluids and did not require renal replacement therapy. He recovered fully and was discharged after 5 days. Serum and urine samples were tested using liquid chromatography time-of-flight mass spectrometry. We detected 4-iodo-2,5-dimethoxyphenethylamine and 4-iodo-2,5-dimethoxy-N-(2-methoxybenzyl) phenethylamine in both serum and urine. No other substances were detected. The 2C drugs and their n-benzyloxymethyl analogs are potent serotonergic agents. Their use has been associated with multiple adverse effects including seizures, rhabdomyolysis, and death. They should be considered in differential diagnosis for drug-induced seizures and as a cause for systemic inflammatory response. This case highlights the significant toxicity seen with these compounds.

Synthetic Cannabinoid and Mitragynine Exposure of Law Enforcement Agents During the Raid of an Illegal Laboratory - Nevada, 2014.

Synthetic cannabinoids (SCs), commonly known by the street name "Spice," are designer drugs of abuse that mimic the psychoactive effects of marijuana. Intentional SC use has resulted in multiple toxicities (1,2), but little is known about occupational SC exposure. After a federal agency's law enforcement personnel in Nevada reported irritability and feeling "high" after raiding illegal SC laboratories and processing seized SCs, a request for a health hazard evaluation was made by the agency to CDC's National Institute for Occupational Safety and Health (NIOSH) in 2014 to evaluate agents' occupational SC exposures. After making the request for a health hazard evaluation, federal agents conducted a raid of an illegal SC laboratory, with assistance from local law enforcement and Drug Enforcement Administration (DEA) personnel and with NIOSH investigators observing from a distance. After the raid, agents collected and processed material evidence. NIOSH investigators tested agents' urine for SC levels before and after the raid and measured SCs in the air and on surfaces after the raid. DEA determined that AB-PINACA (an SC compound) and mitragynine (a plant material with opium-like effects, also known as "kratom") were present in the illegal laboratory. AB-PINACA, its metabolites, and mitragynine were not detected in agents' urine before the raid; however, one or more of these substances was found in the urine of six of nine agents after the raid and processing of the SC evidence. AB-PINACA was detected in one surface wipe sample from the SC laboratory; none was detected in the air in the laboratory or in the offices of the law enforcement agency where the materials were processed after the raid. No policies were in place regarding work practices and use of personal protective equipment (PPE) during raids and evidence processing. To protect agents from SC exposures, NIOSH recommended that the agency require agents to wear a minimum level of PPE (e.g., protective gloves and disposable clothing) and undergo training in PPE and in handling and storing of contaminated evidence from SC laboratory raids. Showers and locker rooms also need to be provided so that agents can reduce contamination and prevent take-home exposure.

Unintentional Pediatric Ingestion of Electronic Cigarette Nicotine Refill Liquid Necessitating Intubation.

Liquid nicotine used in electronic cigarette devices is highly concentrated, unreliably packaged, and poorly regulated. We present a case report of a 6-year-old female who developed severe toxicity and required intubation after an unintentional oral ingestion of approximately 703 mg (35 mg/kg) of liquid nicotine, with accompanying serum and urine concentrations of nicotine and its metabolites. Analysis of the ingested liquid suggests a nicotine concentration of 140.6 mg/mL in the purchased commercial product, or 234% of its labeled concentration. Clinicians should be aware of these products and the potential severity of toxicity they may incur.