Bruce A. Goldberger

Event-level analyses of energy drink consumption and alcohol intoxication in bar patrons

AIM To assess event-level associations between energy drink consumption, alcohol intoxication, and intention to drive a motor vehicle in patrons exiting bars at night. METHOD Alcohol field study. Data collected in a U.S. college bar district from 802 randomly selected and self-selected patrons. Anonymous interview and survey data were obtained as well as breath alcohol concentration (BrAC) readings. RESULTS Results from logistic regression models revealed that patrons who had consumed alcohol mixed with energy drinks were at a 3-fold increased risk of leaving a bar highly intoxicated (BrAC> or =0.08g/210L), as well as a 4-fold increased risk of intending to drive upon leaving the bar district, compared to other drinking patrons who did not consume alcoholic beverages mixed with energy drinks. DISCUSSION These event-level associations provide additional evidence that energy drink consumption by young adults at bars is a marker for elevated involvement in nighttime risk-taking behavior. Further field research is needed to develop sound regulatory policy on alcohol/energy drink sales practices of on-premise establishments.

“Bath Salts” Intoxication

This letter highlights recreational ingestion of bath salts containing methylenedioxypyrovalerone, a potent central nervous system stimulant. Intoxication that results in extreme sympathetic stimulation and profoundly alters mental status may be fatal.

Comparison between self-report and hair analysis of illicit drug use in a community sample of middle-aged men

Discrepancies between biological assays and self-report of illicit drug use could undermine epidemiological research findings. Two objectives of the present study are to examine the degree of agreement between self-reported illicit drug use and hair analysis in a community sample of middle-aged men, and to identify factors that may predict discrepancies between self-report and hair testing. Male participants followed since 1972 were interviewed about substance use, and hair samples were analyzed for marijuana, cocaine, opiates, phencyclidine (PCP) and methamphetamine using radioimmunoassay and gas chromatography-mass spectrometry (GC-MS) techniques. Self-report and hair testing generally met good, but not excellent, agreement. Apparent underreporting of recent cocaine use was associated with inpatient hospitalization for the participants most recent quit attempt, younger age, identifying as African American or other, and not having a diagnosis of antisocial personality disorder. The overestimate of marijuana use relative to hair test was associated with frequent use since 1972 and providing an inadequate hair sample. Additional research is needed to identify factors that differentially affect the validity of both hair drug testing and self-report.

Fatal Case of BOTOX®-Related Anaphylaxis?

Anaphylactic drug reactions are rare and often serious events. The Botulinum toxin A, marketed as BOTOX, was recently approved by the Food and Drug Administration for cervical dystonia and glabellar wrinkles, after its approved use and success with blepharospasm, strabismus, and disorders of the 7th cranial nerve. It has been well received due to its efficacy in improving facial lines. This case report documents the first death associated with a Botox-lidocaine mixture given to a woman for chronic neck and back pain. Based on the medical records, autopsy, and laboratory findings, the cause of death was determined to be anaphylaxis to the Botox-lidocaine mixture. The history, indications, off-label uses and possible future applications of Botox are reviewed as well as the uses and complications of lidocaine. Although the anaphylaxis cannot be definitively proven to be due to Botox alone, this case warns of an adverse reaction related to Botox, a drug that is rapidly expanding in range of use as well as increased usage.

Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015.

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEAs National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(†) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(§) and recent release from an institution such as a jail, rehabilitation facility, or hospital.

Abrupt decline in oxycodone-caused mortality after implementation of Florida's Prescription Drug Monitoring Program.

BACKGROUND In Florida, oxycodone-caused deaths declined substantially in 2012. Multiple important law enforcement, pharmaceutical, policy, and public health actions occurred concurrently, including implementation of a statewide Prescription Drug Monitoring Program (PDMP). The effects of the PDMP on oxycodone-caused mortality in Florida were evaluated. METHODS A time-series, quasi-experimental research design with autoregressive integrated moving average (ARIMA) statistical models, including internal and external covariates. Data included 120 repeated monthly observations. Monthly counts of oxycodone-caused deaths, obtained from the Florida Medical Examiners Commission (MEC) was the outcome variable. Models included market-entry of tamper-resistant oxycodone HC1 controlled release tablets (OxyContin(®)), enforcement crackdowns (Operation Pill Nation), and regulation by FL House Bill 7095, measured by the monthly count of Florida pain management clinics closed. Two approaches were used to test the PDMPs hypothesized effect: (1) a binary indicator variable (0=pre-implementation, 1=post-implementation), and (2) a continuous indicator consisting of the number of PDMP queries by health care providers. RESULTS Oxycodone-caused mortality abruptly declined 25% the month after implementation of Floridas PDMP (p=0.008). The effect remained after integrating other related historical events into the model. Results indicate that for a system-wide increase of one PDMP query per health care provider, oxycodone-caused deaths declined by 0.229 persons per month (p=0.002). CONCLUSIONS This is the first study to demonstrate that the PDMP had a significant effect in reducing oxycodone-caused mortality in Florida. Results have implications for national efforts to address the prescription drug epidemic.

Identification of cocaine analytes in fingernail and toenail specimens.

Fingernail and toenail specimens were obtained from 18 suspected cocaine users. The nails were cut, heated under methanolic reflux, and the methanolic extracts were purified by solid-phase extraction. Gas chromatography/mass spectrometry was utilized for the qualitative and quantitative analysis of nine cocaine analytes. Comparison of conventional postmortem analysis of blood and urine with nail analysis revealed a marked increase in the detection of cocaine use by nail analysis. Cocaine analytes were present in 14 (82.3%) subjects utilizing nail analysis. Out of those 14 subjects, only 5 (27.7%) were positive by conventional postmortem drug analysis. Cocaine and benzoylecgonine were the predominant analytes in all positive nail specimens. Anhydroecgonine methyl ester, ecgonine methyl ester, ecgonine ethyl ester, cocaethylene, norcocaine, and norbenzoylecgonine were detected in a limited number of specimens. The ratio of cocaine to benzoylecgonine ranged from 2-10:1. These findings suggest that nails may be a useful alternative matrix for the detection of cocaine exposure.

Methadone- and heroin-related deaths in Florida.

Methadone is a potent synthetic opioid used for treatment of opioid dependence and chronic pain. Florida Department of Law Enforcement data were analyzed to examine trends in deaths related to or caused by methadone and/or heroin between 2001–2006. Results demonstrated that mortalities associated with methadone use increased steadily as mortalities associated with heroin decreased steadily. Though useful in the treatment of opioid dependence and chronic pain, methadone possesses high abuse potential and documented mortality risks. Treatment with methadone, for both pain and opioid dependence, should be preceded by an abuse liability evaluation. Attempts to minimize diversion should be implemented.

Detection of Cocaine and Its Metabolites in Breast Milk

A method was developed for measuring cocaine and its metabolites, benzoylecgonine, ecgonine methyl ester, norcocaine, ecgonine ethyl ester, cocaethylene, and m-hydroxybenzoylecgonine, in breast milk by gas chromatography/mass spectrometry. Limits of detection for this method ranged from 2.5 to 10 ng/mL, and limits of quantitation ranged from 5 to 50 ng/mL. For each of the compounds measured by this method, linear response was demonstrated to 750 ng/mL. Breast milk was collected from 11 mothers who admitted to drug use during pregnancy and ten drug-free volunteers serving as control subjects. Cocaine was detected in six of the specimens obtained from drug-exposed subjects, and in none of the drug-free control subjects. In breast milk specimens where cocaine and one or more of its metabolites were detected, the concentration of parent compound was greater than any of the metabolites. The highest cocaine concentration found was over 12 microg/mL. Breast-fed infants of cocaine abusing mothers may be exposed to significant amounts of drug orally.

Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016

Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July-December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDCs Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.