Acetyl Fentanyl Toxicity: Two Case Reports.

Acetyl fentanyl is an illicit fentanyl analog recently appearing in forensic casework. A quantitative method was created for measuring acetyl fentanyl in various biological matrices acquired post-mortem due to recent positive screening results in casework. Initial detection by immunoassay and standard gas chromatography mass spectrometry (GC/MS) methods have been previously reported for acetyl fentanyl and are examined further here. A Selective Ion Monitoring (SIM) method was created using a GC/MS for quantitation. In two separate cases, acetyl fentanyl was found to be in similar concentrations to those previously reported and ruled to be the cause of death. Acetyl fentanyl concentrations were determined in blood samples, liver, brain, vitreous humor, and urine. Individual 1 had acetyl fentanyl concentrations as follows: heart blood-285 ng/mL, femoral blood-192 ng/mL, liver-1,100 ng/g, brain-620 ng/g, and urine-3,420 ng/mL. Individual 2 had acetyl fentanyl concentrations as follows: heart blood-210 ng/mL, femoral blood-255 ng/mL, urine-2,720 ng/mL and vitreous humor-140 ng/mL. Experimental conditions for screening and quantitation are provided, using immunoassay and GC/MS methods. Due to the recent emergence of acetyl fentanyl, more data will need to be generated to fully differentiate recreational and fatal concentrations of acetyl fentanyl to assist toxicologists accurately understanding its physiological impact.

Reducing opioid analgesic deaths in America: what health providers can do.

BACKGROUND: Available data have shown steady increases of drug overdose deaths between 1992 and 2011. We review evidenced-based recommendations provided by a few prominent North American pain societies and suggest ways on how health providers might help reduce opioid analgesic deaths by implementing these practices. OBJECTIVE: To identify health care providers' roles in reducing opioid analgesic deaths. STUDY DESIGN: A comprehensive review of current literature. METHODS: The review included relevant literature identified through searches of MEDLINE, Cochran reviews, and Google Scholar, PubMed and EMBASE from January 1998 to January 2014. The level of evidence was classified as I (good), II (fair), and III (limited) based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). RESULTS: Several practices such as too high doses overall, giving too high doses to opioid naive patients, too fast opioid titration, insufficient use and knowledge of urine drug testing, not updating knowledge of drug metabolism/interactions, and inadequate patient monitoring are associated with higher risks of opioid analgesic deaths. Suboptimal risk stratification of patients, rotation practices, and use of opioids analgesics in chronic noncancer pain are also associated factors. LIMITATIONS: There were a paucity of good evidence studies which show recommendations reduce death. CONCLUSION: Providers should be aware of all associated factors with opiate analgesic deaths and apply the available evidence in reducing opioid analgesic deaths.

Concentrations of cocaine and benzoylecgonine in femoral blood from cocaine-related deaths compared with venous blood from impaired drivers.

The concentrations of cocaine and its major metabolite benzoylecgonine (BZE) were determined in femoral blood from 132 cocaine-related deaths and compared with venous blood from 988 apprehended drivers. Cocaine and BZE were determined by solid-phase extraction and isotope dilution gas chromatography-mass spectrometry with limits of quantitation of 0.02 mg/L for both substances. Significantly more men (95-98%) than women (2-5%) abused cocaine, although their mean age was about the same (29-30 years). Mean age (±SD) of cocaine-related deaths was 29 ± 7 years, which was not significantly different from 30 ± 8 years in traffic cases (P > 0.05). The median concentration of cocaine in blood in 61 fatalities was 0.10 mg/L compared with 0.06 mg/L in traffic cases (P < 0.001). In drug intoxication deaths, the median concentration of cocaine was 0.13 mg/L (N = 25), which was not significantly different from 0.09 mg/L (N = 36) in other causes of death. Cocaine-related deaths mostly involved mixed drug intoxications including co-ingestion of heroin, cannabis, amphetamines as well as legal drugs, such as benzodiazepines and/or ethanol. The concentrations of cocaine in blood from living and deceased persons overlapped, which makes it infeasible to predict toxicity from the analytical toxicology results alone.

The Fagerström test for nicotine dependence: do revisions in the item scoring enhance the psychometric properties?

Despite widespread use, considerable literature has shown that the Fagerström Test for Nicotine Dependence (FTND; Heatherton, Kozlowski, Frecker, & Fagerström, 1991) has questionable psychometric properties, generally reflecting relatively poor properties of reliability and validity. One factor that may be affecting the psychometric qualities of the scale is the use of a dichotomous, forced-choice response format for certain items, in which respondents are asked to answer each question with a Yes or No response. This scoring approach is especially problematic when used to measure dimensional constructs, such as nicotine dependence, in which a dimensional construct is forced into a categorical construct. The purpose of the current study was to examine whether revising the response format utilized in the FTND would lead to an enhancement in the psychometric properties of this scale. This question was examined by removing the forced-choice response criteria on items 2, 5, and 6 of the FTND and revising the response options to reflect a 4-point Likert response set (0 = never, 1 = sometimes, 2 = most of the time, 3 = always). Participants consisted of 343 smokers from the community. Results revealed that the revised scoring approach resulted in a significant incremental improvement in scale reliability and enhanced convergent validity, showing a stronger association with smoking outcomes than the FTQ or FTND. Findings are discussed in terms of recommendations for scale revision and usage.

Interpretation of postmortem forensic toxicology results for injury prevention research.

Forensic toxicological data provides valuable insight into the potential contribution of alcohol and drugs to external-cause deaths. There is a paucity of material that guides injury researchers on the principles that need to be considered when examining the presence and contribution of alcohol and drugs to these deaths. This paper aims to describe and discuss strengths and limitations of postmortem forensic toxicology sample selection, variations in analytical capabilities and data interpretation for injury prevention research. Issues to be considered by injury researchers include: the circumstances surrounding death (including the medical and drug use history of the deceased person); time and relevant historical factors; postmortem changes (including redistribution and instability); laboratory practices; specimens used; drug concentration; and attribution of contribution to death. This paper describes the range of considerations for testing and interpreting postmortem forensic toxicology, particularly when determining impairment or toxicity as possible causal factors in injury deaths. By describing these considerations, this paper has application to decisions about study design and case inclusion in injury prevention research, and to the interpretation of research findings.

Methadone-related fatalities: review in the Ghent district between 1978-2008.

Previous research demonstrated that Methadone Maintenance Programs (MMP) and Methadone Maintenance Treatment/Therapy (MMT) could significantly reduce the mortality risk. However, in current forensic practice, methadone ingestion can still directly or indirectly be involved in fatalities. The objectives of this study were twofold. Firstly, referring to the wide range of blood levels reported in methadone-related fatalities, we aimed to provide insight into the interpretation of a quantitative post-mortem blood concentration. Secondly, to examine and discuss possible causes, mechanisms and manners of death. During a 30-year-period, all medico-legal files at the Department of Forensic Medicine (Ghent University) were searched through, to investigate whether methadone was involved in the fatal outcome. A significant increase in the methadone-related fatalities was found since 1995, which has also been noticed in other studies. In our study (n=48), the most frequent cause of death was intoxication: only one was due to a pure methadone intoxication, whereas in all other fatal intoxications, a poly-drug intoxication was found. In this study, cardiopulmonary failure, induced by depression of the vital centres in the brainstem, was--as expected--the most important mechanism of death. When we considered the post-mortem blood levels in our study group, we observed a wide range, namely between 0.10 and 4.13 microg/ml (median: 0.54 microg/ml, mean: 0.81 microg/ml, SD: 0.14). This was in line with previous reports, although the extreme values differed. We conclude that the interpretation of post-mortem methadone blood levels is still hazardous due to e.g. difficulties to assess the individual tolerance level, the variety of surviving periods after ingestion, interfering post-mortem redistribution and the combined ingestion of methadone with other drugs. Therefore, a close collaboration between the forensic pathologist and toxicologist is recommended in order to provide a well-grounded conclusion.

[Forensic-medical diagnostic implication of morphine levels in the blood and urine].

Toxicological characteristics are presented for 198 cases of acute parenteral poisoning with morphine and heroin. The range of their metabolites concentration in the blood and urine encountered in practice are analysed. Principal causes of death due to opiate poisoning in inpatients are shown. Opiates toxicity was assessed by the method of logit-regression and dose-effect curves for analysis of probability of death depending on opiate metabolite concentration in blood and urine. Relations between probability of death and detection of morphine in biological media of the victims are considered. Morphine concentrations in the blood and urine undoubtedly indicating morphine poisoning are determined.