Using Forensic Toxicology to Enhance Medicolegal Death Investigations.

ABSTRACT: The Milwaukee County Medical Examiner's Office performed an evidence-based review of natural deaths certified without autopsy or toxicology testing. Three hundred fifteen such cases from 2020 and 2021 were selected. This study reviewed the deaths to determine if the cause was drug-related instead due to natural disease.Blood samples were screened by liquid chromatography-quadrupole mass spectrometry with time-of-flight detector. The analytes detected were evaluated for contribution to the cause resulting in a change in manner from natural to accident or suicide. Confirmatory analysis was performed where appropriate, and results were reported to the forensic pathologist for evaluation. Where appropriate, the death certificate was amended.As a result of the screening and confirmatory work, 18 cases were identified where significant drugs were detected, and thus the cause and manner of death were amended. One case was amended from natural to suicide after a conversation with the family about the toxicology findings. The remaining cases were amended to a manner of accident. The scope of drugs responsible for the deaths included prescription and illicit.

Case Report of Lethal Concentrations of the Over-the-Counter Sleep Aids Diphenhydramine and Melatonin.

ABSTRACT: Over-the-counter (OTC) medications are not typically considered "drugs of abuse" by the public, yet they are implicated in a portion of overdose cases. Although the toxicity of some OTC medications (such as acetaminophen, aspirin, and diphenhydramine [DPH]) has been extensively reported in the medical literature, the lethality of other substances (including melatonin) has not been well established.We report the case of a 21-year-old woman who was found deceased within her secure residence. Scene investigation revealed the presence of 5 empty containers of DPH and a partially empty container of melatonin, as well as a handwritten note of apparent suicidal nature. Upon autopsy examination, the gastric mucosa was notable for a green-blue discoloration, and the gastric contents were consisted of a green-tan viscous material with admixed blue particulate material. Further analysis revealed elevated concentrations of both DPH and melatonin within the blood and gastric contents. The death was certified as a suicide by acute combined DPH and melatonin toxicity.This paper will review the pharmacology of OTC sleep aid medications and provide a brief outline of their documented toxicity, in addition to reinforcing the role of death scene investigation and its correlation with autopsy findings.

Shift in Drug vs Alcohol Prevalence in Milwaukee County Motor Vehicle Decedents, 2010-2016.

OBJECTIVE: The purpose of this study is to examine the prevalence of alcohol and nonalcohol drugs in motor vehicle crash (MVC) decedents in Milwaukee County, Wisconsin. METHODS: A retrospective review of MVC decedents in Milwaukee County from 2010 to 2016 was performed. Substances were divided into 5 categories based on chemical composition and clinical effects: alcohol, cocaine and its metabolite benzoylecgonine, opioids, cannabinoids, amphetamines and methamphetamines. Decedents were determined to be positive if any of these substances were detected on blood toxicology analysis. RESULTS: Sixty-five percent (n = 113) of MVC decedents tested positive for 1 substance, while polysubstance use (≥ 2 substances) was seen in 27% (n = 47). Alcohol was the most prevalent substance (n = 77, 44%), while cannabinoids were the second most prevalent (n = 50, 29%), and opioids were third most prevalent (n = 24, 14%). There was a statistically significant increase in the number of MVC decedents who tested positive for opioids from 2010 to 2016 (slope = 3.9, P < 0.01). The number of decedents who tested positive for alcohol only from 2010 to 2016 decreased significantly (slope = -3.9, P < 0.05), and 2016 was the first year in which the number of drug-positive decedents exceeded the number of alcohol-positive decedents. CONCLUSION: The prevalence of drugs exceeded that of alcohol in decedents for the first time in 2016 in Milwaukee County. While continued efforts to reduce alcohol-positive driving are encouraged, increased attention to drugged driving is needed to prevent further drug-positive fatalities.

Urine Drug Screening in the Era of Designer Benzodiazepines: Comparison of Three Immunoassay Platforms, LC-QTOF-MS and LC-MS-MS.

This study investigated the presence of designer benzodiazepines in 35 urine specimens obtained from emergency department patients undergoing urine drug screening. All specimens showed apparent false-positive benzodiazepine screening results (i.e., confirmatory testing using a 19-component liquid chromatography-tandem mass spectrometry (LC-MS-MS) panel showed no prescribed benzodiazepines at detectable levels). The primary aims were to identify the possible presence of designer benzodiazepines, characterize the reactivity of commercially available screening immunoassays with designer benzodiazepines and evaluate the risk of inappropriately ruling out designer benzodiazepine use when utilizing common urine drug screening and confirmatory tests. Specimens were obtained from emergency departments of a single US Health system. Following clinically ordered drug screening using Abbott ARCHITECT c assays and laboratory-developed LC-MS-MS confirmatory testing, additional characterization was performed for investigative purposes. Specifically, urine specimens were screened using two additional assays (Roche cobas c502 and Siemens Dimension Vista) and LC-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) to identify presumptively positive species, including benzodiazepines and non-benzodiazepines. Finally, targeted, qualitative LC-MS-MS was performed to confirm the presence of 12 designer benzodiazepines. Following benzodiazepine detection using the Abbott ARCHITECT, benzodiazepines were subsequently detected in 28/35 and 35/35 urine specimens using Siemens and Roche assays, respectively. LC-QTOF-MS showed the presumptive presence of at least one non-Food and Drug Administration (FDA)-approved benzodiazepine in 30/35 specimens: flubromazolam (12/35), flualprazolam (11/35), flubromazepam (2/35), clonazolam (4/35), etizolam (9/35), metizolam (5/35), nitrazepam (1/35) and pyrazolam (1/35). Two or three designer benzodiazepines were detected concurrently in 13/35 specimens. Qualitative LC-MS-MS confirmed the presence of at least one designer benzodiazepine or metabolite in 23/35 specimens, with three specimens unavailable for confirmatory testing. Urine benzodiazepine screening assays from three manufacturers were cross-reactive with multiple non-US FDA-approved benzodiazepines. Clinical and forensic toxicology laboratories using traditionally designed LC-MS-MS panels may fail to confirm the presence of non-US FDA-approved benzodiazepines detected by screening assays, risking inappropriate interpretation of screening results as false positives.

Volumetric arterial enhancement fraction predicts tumor recurrence after hepatic radiofrequency ablation of liver metastases: initial results.

OBJECTIVE: The objective of our study was to investigate the diagnostic value of the volumetric arterial enhancement fraction of the liver with color mapping for the early detection of tumor relapse after hepatic radiofrequency ablation (RFA). MATERIALS AND METHODS: Fifty-three patients (24 men, 29 women; mean age ± SD, 65 ± 10 years) with a total of 215 liver metastases treated by RFA and a mean postinterventional follow-up period of 20 ± 15 (SD) months were included in this retrospective study. Quantitative arterial enhancement fraction color maps of the whole liver were computed from triple-phase contrast-enhanced MDCT images. Follow-up examinations served as the standard of reference. The diagnostic performance of the arterial enhancement fraction color maps to predict subsequent tumor occurrence before tumor was visible on routine multiphase CT images was evaluated. RESULTS: The mean arterial enhancement fraction of segments that developed metastases (62% ± 23%) was significantly higher than the mean of segments that did not develop metastases (39% ± 20%) (p < 0.0001). Receiver operating characteristic curve analysis revealed a probability of 77% for arterial enhancement fraction values to be higher in case of subsequent metastases as compared with liver parenchyma without tumor recurrence. CONCLUSION: The arterial enhancement fraction provides incremental value in the imaging surveillance for liver metastases after RFA. Arterial enhancement fraction color maps may be suited to predict tumor recurrence earlier than routine assessment using contrast-enhanced MDCT.

Opioid Deaths in Milwaukee County, Wisconsin 2013-2017: The Primacy of Heroin and Fentanyl.

Heroin and fentanyl are the overwhelming and increasing cause of opioid deaths in Milwaukee County, Wisconsin. We reviewed all drug and opioid deaths from 2013 to 2017 to delineate the specific opioid drugs involved and changes in their incidence. From 2013 to 2017, 980 deaths were due to opioids, rising from 184 in 2013 to 337 in 2017. In 2017, opioid deaths exceeded combined non-natural deaths from homicide and suicide. Illicit heroin and fentanyl/analogs caused 84% of opioid deaths and 80% of drug deaths, with no increase in deaths due to oral prescription drugs such as oxycodone and hydrocodone. Any approach to decreasing this dramatic increase in opioid deaths should first focus on interdicting the supply and cheap availability of these illicit opioids. Fentanyl and its analogs represent the most deadly opioids and the greatest threat to human life in our population.