Toxicology Reports Research Articles

Prediction of Alternative Drug-Induced Liver Injury Classifications Using Molecular Descriptors, Gene Expression Perturbation, and Toxicology Reports.

Motivation: Drug-induced liver injury (DILI) is one of the primary problems in drug development. Early prediction of DILI, based on the chemical properties of substances and experiments performed on cell lines, would bring a significant reduction in the cost of clinical trials and faster development of drugs. The current study aims to build predictive models of risk of DILI for chemical compounds using multiple sources of information.Methods: Using several supervised machine learning algorithms, we built predictive models for several alternative splits of compounds between DILI and non-DILI classes. To this end, we used chemical properties of the given compounds, their effects on gene expression levels in six human cell lines treated with them, as well as their toxicological profiles. First, we identified the most informative variables in all data sets. Then, these variables were used to build machine learning models. Finally, composite models were built with the Super Learner approach. All modeling was performed using multiple repeats of cross-validation for unbiased and precise estimates of performance.Results: With one exception, gene expression profiles of human cell lines were non-informative and resulted in random models. Toxicological reports were not useful for prediction of DILI. The best results were obtained for models discerning between harmless compounds and those for which any level of DILI was observed (AUC = 0.75). These models were built with Random Forest algorithm that used molecular descriptors.

Substance use and deaths by suicide: A latent class analysis of the National Violent Death Reporting System

Substance use is strongly associated with suicide completions. However, little is known about the patterns of substances used in suicide deaths. The purpose of this analysis is to determine latent classes of toxicology-reported substances among individuals who completed suicide. The sample consists of suicide victims in the National Violent Death Reporting System (NVDRS) during years 2003–2017 (n = 202,838). Toxicology reports were used to construct latent class analyses of substance use among suicide victims. Correlates for latent class membership included sex, race/ethnicity, previous experiences of child abuse, homelessness, and intimate partner violence (IPV) victimization. The majority of suicide victims were male (77.7%), straight/heterosexual (99.5%) and white (88.3%). The final unconditional model yielded a four-class model, including a “No substance/single substance use” class, an “Alcohol and other substance” class, a “Marijuana and other substance” class, and an “Opiate use” class. Compared to the reference class of “No substance/single substance,” females were more likely than males to be classified in the “Alcohol and other substance” class, the “Multi-substance use” class, and the “Opiate use” class. Homelessness was associated with classification in the “Marijuana and other substance” class and the “Opiate use” class compared to the “No substance/single substance” class. IPV was associated with both polysubstance use classes (“Alcohol plus other substance” and “Marijuana plus other substance”) along with the “Opiate use” class compared to the “No substance/single substance” class. These classes highlight profiles of suicide descendants and emphasize the importance of polysubstance use prevention among females, homeless individuals, and those who experience IPV.

Kratom-Associated Fatalities in Northern Nevada—What Mitragynine Level Is Fatal?

Mitragyna speciosa, commonly known as the kratom tree, has been utilized in Southeast Asia for centuries for its opioid-like effects. Kratom has been available in the United States for the past decade and has grown increasingly popular despite a lack of clinical research to determine its safety. With its widespread use, there have been an increasing number of fatalities. This study aims to establish a potential lethal range for mitragynine, the active compound in kratom, by investigating the toxicology reports of 35 deaths in Northern Nevada between 2015 and 2020. Mitragynine concentrations ranged from 8.7 to 1800 ng/mL (n = 27) in cases with drug toxicity as the cause of death; in 1 case, the sole intoxicant was mitragynine with a blood concentration of 950 ng/mL. In cases with nonmitragynine causes of death, the concentration was 110 to 980 ng/mL (n = 8). There was no statistically significant difference in blood concentrations between cases where mitragynine was not listed as a cause of death (mean, 315 ± 297.2 ng/mL) and cases in which mitragynine contributed to death (mean, 269.4 ± 382.5 ng/mL; P < 0.201). A literature review is also presented.

Conversations about structural racism are uncomfortable. That’s the point.

Conversations about structural racism are uncomfortable. That’s the point.

Accidental Deaths Involving Trees: Professional and Nonprofessional Woodcutting and Tree Failures With Autopsy Findings.

We examined all deaths in Connecticut involving tree mishaps (struck by a tree/tree limb, injuries associated with tree removal operations). Records of the Connecticut Office of the Chief Medical Examiner including autopsy, toxicology, and investigators' reports of deaths from 2004 to 2019 were reviewed. All underwent autopsy examination.There were 64 fatalities, with ages ranging from 4 to 90 years (mean, 50 years). The causes of death involved the following: 56 blunt injury (primary site: 25 head, 13 multiple locations, 11 torso, and 7 neck), 5 traumatic asphyxia, 2 electrocution, and 1 chainsaw injury. Deaths were classified into 3 groups: 21 nonprofessional woodcutters, 19 professional woodcutters, and 24 tree failures. Among all woodcutters (100% men), impact by a falling tree/limb (78%) was the most common fatal event, and the most common lethal injury site was the head (45%). For tree failures, 58% involved storm/high-wind events, whereas 42% were spontaneous. Of the tree failure events, 58% involved motor vehicles, with most (86%) occurring while driving. Ethanol was detected in 6 decedents with blood concentrations ranging from 0.02 to 0.19 gm%, of which 4 were nonprofessional and 2 were professional woodcutters. There were some seasonal differences among the 3 groups.Overall, fatalities of nonprofessional woodcutters, compared with professionals, were more likely to involve an older man (58 vs 40 years), working alone (67% vs 11%), and under the influence of ethanol (19% vs 11%) in late summer-autumn who dies of blunt head trauma from a falling tree or tree limb. Aggressive tree control management along highways has been used to attempt to decrease storm-related fatalities.

Community overdose surveillance: Comparing substances collected from the death scene investigation to toxicology results

BackgroundRecent overdose trends are characterized by increased toxicological detection of stimulants with opioids, yet it is unclear whether these substances are mixed prior to consumption or purposefully used simultaneously. MethodsPostmortem toxicology data were collected in Marion County, Indiana, from 45 fatal overdose cases involving heroin, fentanyl, methamphetamine, or cocaine. Substances found by death scene investigators at the scene of the fatal overdose (57 samples) were tested using high-pressure liquid chromatography mass-spectrometry (LC–MS) technology. We compared toxicology and LC–MS results to understand whether substances contributing to overdose were found in combination or separately at the scene of the overdose. ResultsComparing toxicology reports with LC–MS results from substances found at the scene of overdose deaths involving opioids and stimulants reveal that deaths are largely the result of the co-use of opioids and stimulants, rather than use of stimulants combined with opioids. ConclusionsCollecting and testing physical samples from fatal overdose scenes and comparing these to post-mortem toxicology results is a new way to examine polydrug use patterns. This community overdose surveillance method can be used to improve overdose prevention and response efforts.

Over-the-counter antihistamines in drug-related deaths: a population-based case series

Abstract Introduction Antihistamines are not one of the medicine groups reported on in the Office for National Statistics drug-related death data. (1) However, there is concern that first-generation antihistamines are misused for their sedative properties. This is amplified by a recent social media challenge, which resulted in deaths due to diphenhydramine overdose. (2) The extent of the involvement of antihistamines in deaths is largely unknown. Aim We aimed to evaluate deaths related to antihistamines in England (2000–2019) by individual drug, medicine classification (POM, P, GSL), whether the drug was considered attributable to the death (known as implication rate), or incidental; and examine temporal trends. Methods Deaths are reported voluntarily by coroners to the National Programme on Substance Abuse Deaths (NPSAD) in cases where psychoactive drugs were detected at post-mortem and/or when the decedent was known to abuse drugs. NPSAD holds data on decedent demographics (gender, age, employment status, living arrangements), details pertaining to the death (cause(s) of death, manner of death, conclusion of inquest, toxicology reports) and past social and medical histories, including drugs prescribed. From this dataset, we extracted all cases where an antihistamine was detected at post-mortem between 2000 and 2019. We report descriptive statistics to describe the reporting of antihistamines in deaths. Results We identified 1666 antihistamine detections from 1537 individuals. The significant majority of these were sedative antihistamines which are classed as pharmacy medicines (P) (85.2%, p&amp;lt;0.01); deaths where prescription-only antihistamines were detected represented fewer than 7.0% of cases. Despite an increasing trend for antihistamine detections in deaths over time, the proportion of deaths where the detected antihistamine was implicated in causing the death declined over the same period (average implication rate 2000–2005: 58.7%; 2014–2019: 28.4%). Whilst death was deemed accidental in the majority of cases (66.1%), a significant proportion of cases were concluded as suicide (20.9%, p&amp;lt;0.01).Polydrug use was evident in the vast majority of cases (98.5%), with central nervous system depressants the most commonly co-administered substances (94.8% of cases). Conclusion We describe the first report regarding antihistamine-related mortality from England. From the NPSAD, we can obtain prescription source and toxicology reports, beyond those reported in national death data. Although incomplete, the response from coroners is good (89%), and provides sufficient cause for concern. The rising trend in antihistamine-related deaths may in-part be contributed to by the perceived negligible dangers associated with antihistamines, both from the general public and professionals. Awareness of the dangerous sedative properties that some antihistamines possess is however heightened in individuals who are deliberately seeking out these effects. An urgent review of sedating antihistamines currently assigned under the P classification is needed to achieve antihistamine harm reduction, balanced against the self-care they enable.

Point process modeling of drug overdoses with heterogeneous and missing data

Opioid overdose rates have increased in the United States over the past decade and reflect a major public health crisis. Modeling and prediction of drug and opioid hotspots, where a high percentage of events fall in a small percentage of space–time, could help better focus limited social and health services. In this work we present a spatial-temporal point process model for drug overdose clustering. The data input into the model comes from two heterogeneous sources: (1) high volume emergency medical calls for service (EMS) records containing location and time but no information on the type of nonfatal overdose, and (2) fatal overdose toxicology reports from the coroner containing location and high-dimensional information from the toxicology screen on the drugs present at the time of death. We first use nonnegative matrix factorization to cluster toxicology reports into drug overdose categories, and we then develop an EM algorithm for integrating the two heterogeneous data sets, where the mark corresponding to overdose category is inferred for the EMS data and the high volume EMS data is used to more accurately predict drug overdose death hotspots. We apply the algorithm to drug overdose data from Indianapolis, showing that the point process defined on the integrated data out-performs point processes that use only coroner data (AUC improvement 0.81 to 0.85). We also investigate the extent to which overdoses are contagious, as a function of the type of overdose, while controlling for exogenous fluctuations in the background rate that might also contribute to clustering. We find that drug and opioid overdose deaths exhibit significant excitation with branching ratio ranging from 0.72 to 0.98.

Mental Disorders, Substance Use Disorders, and Psychotropic Medication Use Among Sudden-Death Victims.

The authors sought to estimate the prevalence of mental and substance use disorders and psychotropic medication prescriptions among working-age sudden-death victims. Using a written protocol, the authors screened for sudden deaths attended by emergency medical services (EMS) in a large metropolitan county in North Carolina from March 1, 2013, to February 28, 2015. Sudden-death cases were adjudicated by three cardiologists. Mental health and chronic disease diagnoses and treatments were abstracted from EMS, medical examiner, toxicology, and autopsy reports and from clinical records for the past 5 years before death. Sudden death was identified for 399 adults ages 18-64 years, 270 of whom had available medical records. Most sudden-death victims were White (63%) and male (65%), had a comorbid condition such as hypertension or respiratory disease, and had a mean±SD age of death of 53.6±8.8 years. Most victims (59%) had at least one mental health or substance use disorder documented in a recent medical record; 76%-78% of victims with a mental disorder had a documented psychotropic medication prescription. However, fewer than one-half (41%) had a documented referral to a mental health professional. The most common diagnostic categories were depressive, anxiety, and alcohol-related disorders. Almost one-half (46%) of the victims had a recent psychotropic prescription, most commonly antidepressants (29%) and benzodiazepines (19%). Mental illness, substance use disorders, and psychotropic medication prescriptions were prevalent among sudden-death victims. The health care needs of these individuals may be better addressed by collaborative care for general medical and mental disorders.

Physician death by suicide in the United States: 2012–2016

Reports of incidence of physician suicide in the United States (US) are outdated. The aims of this research were to assess incidence, methods, and associated risk factors of physicians compared to non-physicians in the general US population. Retrospective suicide data (victim age 25 and over) from the 2012–2016 National Violent Death Reporting System were analyzed to test for differences in rates, methods, and risk factors of male and female physicians to non-physicians. The dataset included 498 physician suicides (403 males and 95 females) and 74,420 non-physicians (57,188 males and 17,232 females). No significant difference was found in suicide incidence between gender and age-adjusted physicians vs. non-physicians, though the female physician rate of suicide appeared higher than female non-physicians. The male to female physician ratio of suicide was about 2:1, whereas the ratio in non-physicians was closer to 4:1. Female physicians used poisoning and hanging most often as a method of suicide, where males used firearms. Depressed mood (as perceived by self or others), mental health problems (defined by a diagnosis of depression, a prescribed antidepressants or toxicology report of antidepressants), poor general medical health, and work-related stressors were more frequently associated with physician than with non-physician suicides. In conclusion, results suggest a possible heightened risk to female physicians, which warrants further investigation. Several physician-specific modifiable suicide risk factors present opportunities for prevention.

Polysubstance Use Common in Buprenorphine Deaths

Polysubstance Use Common in Buprenorphine Deaths

Human Poisoning from Poisonous Higher Fungi: Focus on Analytical Toxicology and Case Reports in Forensic Toxicology.

Several families of higher fungi contain mycotoxins that cause serious or even fatal poisoning when consumed by humans. The aim of this review is to inventory, from an analytical point of view, poisoning cases linked with certain significantly toxic mycotoxins: orellanine, α- and β-amanitin, muscarine, ibotenic acid and muscimol, and gyromitrin. Clinicians are calling for the cases to be documented by toxicological analysis. This document is therefore a review of poisoning cases involving these mycotoxins reported in the literature and carries out an inventory of the analytical techniques available for their identification and quantification. It seems indeed that these poisonings are only rarely documented by toxicological analysis, due mainly to a lack of analytical methods in biological matrices. There are many reasons for this issue: the numerous varieties of mushroom involved, mycotoxins with different chemical structures, a lack of knowledge about distribution and metabolism. To sum up, we are faced with (i) obstacles to the documentation and interpretation of fatal (or non-fatal) poisoning cases and (ii) a real need for analytical methods of identifying and quantifying these mycotoxins (and their metabolites) in biological matrices.

Adversity Considerations for Thyroid Follicular Cell Hypertrophy and Hyperplasia in Nonclinical Toxicity Studies: Results From the 6th ESTP International Expert Workshop.

The European Society of Toxicologic Pathology organized an expert workshop in May 2018 to address adversity considerations related to thyroid follicular cell hypertrophy and/or hyperplasia (FCHH), which is a common finding in nonclinical toxicity studies that can have important implications for risk assessment of pharmaceuticals, food additives, and environmental chemicals. The broad goal of the workshop was to facilitate better alignment in toxicologic pathology and regulatory sciences on how to determine adversity of FCHH. Key objectives were to describe common mechanisms leading to thyroid FCHH and potential functional consequences; provide working criteria to assess adversity of FCHH in context of associated findings; and describe additional methods and experimental data that may influence adversity determinations. The workshop panel was comprised of representatives from the European Union, Japan, and the United States. Participants shared case examples illustrating issues related to adversity assessments of thyroid changes. Provided here are summary discussions, key case presentations, and panel recommendations. This information should increase consistency in the interpretation of adverse changes in the thyroid based on pathology findings in nonclinical toxicity studies, help integrate new types of biomarker data into the review process, and facilitate a more systematic approach to communicating adversity determinations in toxicology reports.

Evaluation and applicability of Alere iCup DX 14 for rapid postmortem urine drug screening at autopsy

Performing point-of-care urine drug screen testing at autopsy by a forensic pathologist may provide an early indication of the presence of analytes of interest during autopsy. An evaluation for the screening of 14 classes of common drugs of abuse in postmortem urine by the point-of-care screening device, Alere iCup DX 14, is presented. One hundred ninety postmortem urine samples were screened with the iCup occurring at autopsy by the forensic pathologist. Positive and negative results obtained from the screening kit were evaluated against confirmatory test results obtained using routine forensic toxicology analyses that employed LC-MS/MS and GC-MS to detect a combination of over 85 common drugs of abuse and medications. Sensitivity for each respective iCup drug class ranged from 66% (buprenorphine) to 100% (methadone, tricyclic antidepressants). Specificity for each respective iCup drug class ranged from 89% (benzodiazepines) to 100% (amphetamines, barbiturates, buprenorphine, 3,4-methylenedioxymethamphetamine, methadone). Positive predictive values ranged from 44% (benzodiazepines) to 100% (amphetamines, barbiturates, buprenorphine, methylenedioxymethamphetamine, methadone), while negative predictive values ranged from 96% (methamphetamine) to 100% (barbiturates, methadone, tricyclic antidepressants). A high false-positive rate was yielded by the benzodiazepine class. The lack of fentanyl screening in the point-of-care device is a significant limitation considering its prolific prevalence in forensic casework. The results obtained in the study should be acknowledged when considering the use of the Alere iCup DX 14 in the context of postmortem casework to help indicate potential drug use contemporaneously with autopsy and when requiring such preliminary results prior to the release of a final forensic toxicology report.

Scuba diving fatalities in Australia 2001 to 2013: Chain of events.

We aimed to identify the possible chain of events leading to fatal scuba diving incidents in Australia from 2001-2013 to inform appropriate countermeasures. The National Coronial Information System was searched to identify scuba diving-related deaths from 2001-2013, inclusive. Coronial findings, witness and police reports, medical histories and autopsies, toxicology and equipment reports were scrutinised. These were analysed for predisposing factors, triggers, disabling agents, disabling injuries and causes of death using a validated template. There were 126 known scuba diving fatalities and 189 predisposing factors were identified, the major being health conditions (59; 47%), organisational/training/experience/skills issues (46; 37%), planning shortcomings (29; 23%) and equipment inadequacies (24; 19%). The 138 suspected triggers included environmental (68; 54%), exertion (23; 18%) and gas supply problems (15; 12%) among others. The 121 identified disabling agents included medical-related (48; 38%), ascent-related (21; 17%), poor buoyancy control (18; 14%), gas supply (17; 13%), environmental (13; 10%) and equipment (4; 3%). The main disabling injuries were asphyxia (37%), cardiac (25%) and cerebral arterial gas embolism/pulmonary barotrauma (15%). Chronic medical conditions, predominantly cardiac-related, are a major contributor to diving incidents. Divers with such conditions and/or older divers should undergo thorough fitness-to-dive assessments. Appropriate local knowledge, planning and monitoring are important to minimise the potential for incidents triggered by adverse environmental conditions, most of which involve inexperienced divers. Chain of events analysis should increase understanding of diving incidents and has the potential to reduce morbidity and mortality in divers.

Characteristics of drowning deaths in an inner city river

A study was undertaken of all drowning deaths that occurred over a 30-year period from 1988 to 2017 in the urban section of the River Torrens, Adelaide, South Australia, an augmented waterway that runs through the central business district. Autopsy records from Forensic Science South Australia (FSSA) were reviewed. There were 34 drownings (0-5 cases/yr) with 28 males and 6 females (M;F=4.6:1), with an age range for males of 18-76yrs (mean 42.0; SD 18.0) and for females of 20-84yrs (mean 69.3; SD 24.5). There were 15 (44%) accidents, 11 (32%) suicides, 1 (3%) homicide and 7 (21%) undetermined. Of the 22 cases during or after 1994 with complete toxicology reports, 10 (45%) had a blood alcohol concentration (BAC) of greater than 0.05% (g/100mL) with an illicit substance detected in 4 (18%) cases: (MDMA (3,4-methylenedioxymethamphetamine), methylamphetamine and THC (delta-9-tetrahydrocannabinol) acid). The presence of various therapeutic drugs was also detected in 10 cases (45%) including temazepam, fluoxetine, diazepam, olanzapine, amitriptyline, carbamazepine, codeine, citalopram and valproate. Although the numbers of cases were not high, the urban portion of the River Torrens had a much higher number of drowning events per kilometre compared to other inland waterways in South Australia such as the Murray River. This is most likely due to the vulnerability that exists for intoxicated individuals in the city from falls into the water and to the availability of the river as a means of suicide to members of the adjacent urban population.

A (im)prescindibilidade do laudo toxicológico definitivo, na condenação pelos crimes de tráfico de drogas, no Tribunal de Justiça do Estado do Pará

O objetivo deste trabalho é analisar o posicionamento do Tribunal de Justiça do Estado do Pará em relação à possibilidade de condenação nos crimes de tráfico de drogas em que o laudo toxicológico definitivo está ausente no processo. Para tanto, será realizada uma pesquisa jurisprudencial nos acórdãos do tribunal, a partir do método dedutivo, considerando o disposto na Lei 11.343/2006 (Lei de Drogas). A hipótese central é a de que o tribunal tem condenado pessoas sem o laudo, como resquício de uma política inquisitorial e proibicionista. No decorrer do artigo serão analisados a moldura inquisitorial do sistema processual penal, os delineamentos da noção de materialidade e verdade e a história da legislação brasileira sobre drogas, em especial a Lei 11.343/2006. Essa pesquisa se apresenta como relevante, ao se considerar que ela diz respeito ao maior tribunal da Região Norte do País e que se está a analisar uma das provas fundamentais para julgamento de um dos crimes que mais aprisiona no Brasil.

Selected Aspects of Ocular Toxicity Studies With a Focus on High-Quality Pathology Reports: A Pathology/Toxicology Consultant's Perspective.

Ocular toxicity studies are the bedrock of nonclinical ocular drug and drug-device development, and there has been an evolution in experience, technologies, and challenges to address that ensures safe clinical trials and marketing authorization. The expectations of a well-designed ocular toxicity study and the generation of a coherent, integrative ocular toxicology report and subreports are high, and this article provides a pathology/toxicology consultant's perspective on achieving that goal. The first objective is to cover selected aspects of study designs for ocular toxicity studies including considerations for contract research organization selection, minipig species selection, unilateral versus bilateral dosing, and in-life parameters based on fit-for-purpose study objectives. The main objective is a focus on a high-quality ocular pathology report that includes ocular histology procedures to meet regulatory expectations and a report narrative and tables that correlate microscopic findings with key ophthalmic findings and presents a clear interpretation of test article-, vehicle-, and procedure-related ocular and extraocular findings with identification of adversity and a pathology peer review. The last objective covers considerations for a high-quality ophthalmology report, which in concert with a high-quality pathology report, will pave the way for a best quality toxicology report for an ocular toxicity study.

An outbreak of deaths associated with AMB-FUBINACA in Auckland NZ.

BackgroundAMB-FUBINACA is a synthetic cannabinoid that has been associated with periodic outbreaks of acute poisonings, but few fatalities. In late May, June and July 2017 Auckland, New Zealand, experienced an outbreak of deaths associated with AMB-FUBINACA that continued at a rate of about 2–3 per month through February 2019. The aim of this study was to define the demographic, circumstantial, pathological and toxicological characteristics of this outbreak.MethodsAll records of the Northern Forensic Pathology Service, Auckland Hospital, were reviewed in which the word “AMB-FUBINACA” was referenced, including initial police reports, autopsy reports and toxicology reports. Recorded data included age, sex, race/ethnicity, times and locations, cause of death, autopsy and toxicology findings, and a brief summary of the circumstances of death. Descriptive statistics were performed using IBM® SPSS® Statistics Version 24 and Microsoft® Excel® Version 14.7.2.FindingsSixty-four cases were identified. One sudden infant death and five cases where cause of death was due to trauma were excluded. Of the remaining 58 cases, 88% were male. Mean age was 42 years. In 95% of the deaths, AMB-FUBINACA alone or in combination with alcohol or another drug was listed as the primary or contributory cause of death. In 41 cases postmortem blood concentrations of AMB-FUBINACA acid were available, ranging from <45 ng/mL to >1000 ng/mL, mean 229 ng/mL, median 140 ng/mL. Comorbidities identified included mixed intoxications (29%), heart disease (47%) and obesity (16%). A mental health diagnosis was reported in 50%, and 40% were on antipsychotic medications.InterpretationThis study presents characteristics, comorbidities and toxicological findings in a unique outbreak of deaths associated with the synthetic cannabinoid AMB-FUBINACA in Auckland, NZ.FundingAll work was funded as part of the usual employment of the authors in their respective institutions. No special funding sources are reported.

Alcohol/Illicit Substance Use in Fatal Motorcycle Crashes

BackgroundThe objective of the current study is to determine how alcohol and illicit substance use contributes to motorcycle crash fatalities by examining the relationship between toxicology levels found postmortem and the behavior of riders and passengers in fatal motorcycle crashes. Materials and methodsAll motorcycle fatalities in Miami-Dade County, FL, from 2009 to 2014 were reviewed using the Miami-Dade County Medical Examiner's toxicology reports and the corresponding crash reports. ResultsPositive alcohol/illicit substance detection was found in 44% of our population of 227 fatalities. When compared with those with a negative alcohol/illicit substance detection, those with a positive alcohol/illicit substance detection were more likely to be found at fault of the crash (77% versus 50%, P < 0.001), more likely to be in a single-vehicle crash (47% versus 21%, P < 0.001) and less likely to wear a helmet (44% versus 64%, P = 0.002). However, there was no significant relationship between speeding and alcohol/illicit substance detection (29% versus 33%, P = 0.748). In addition, a regression analysis demonstrated that there was less helmet use and more single-vehicle crashes with higher blood alcohol concentration. ConclusionsIn fatal motorcycle crashes, alcohol and illicit substance use had a significantly negative impact on the risk aversion of motorcycle fatalities in regard to fault, helmet use, and single-vehicle crashes.