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Circumstances, Postmortem Findings, Blood Concentrations and Metabolism in a Series of Methoxyacetylfentanyl-Related Deaths.

ABSTRACT: Methoxyacetylfentanyl is one of many fentanyl analogs available as new psychoactive substances. It have been encountered in both the European Union and the United States, and existing literature suggest that methoxyacetylfentanyl is around 3- to 5-fold less potent than fentanyl. The aim of the present work was to combine case information with blood concentrations and abundance of urinary metabolites to investigate the importance of these parameters for toxicological interpretation. Quantification of methoxyacetylfentanyl in femoral blood was performed by LC--MS-MS and urinary metabolites were analyzed by LC--QTOF-MS with and without hydrolysis with β-glucuronidase/arylsulfatase. For confirmation of identified metabolites, methoxyacetylfentanyl was incubated with hepatocytes for up to 5 hours and analyzed with the same method as the urine samples. In eleven postmortem cases (27 to 41 years old and including one female) methoxyacetylfentanyl was reported in femoral blood. The cause of death was intoxication by methoxyacetylfentanyl alone or in combination with other drugs in all but one case, where death was attributed to acute complications of an underlying heart disease but with possible contribution from methoxyacetylfentanyl. In total, 27 urinary metabolites were found, including eight glucuronides. Major biotransformations were O-demethylation, dealkylation to form the nor-metabolite, mono- and dihydroxylations of the phenethyl moiety, as well as combinations thereof. The most abundant metabolites in hydrolyzed urine included O-desmethyl-, O-desmethyl-phenethyl-hydroxy-, O-desmethyl-phenethyl-hydroxymethoxy- and nor-methoxyacetylfentanyl. Differences in the abundance of methoxyacetylfentanyl and its major metabolites could be interpreted to indicate fatal intoxications in abstinent or chronic users. We postulate that urinary concentrations of methoxyacetylfentanyl and two metabolites, in combination with the methoxyacetylfentanyl concentration in femoral blood, might be good indicators of the time between administration and death as well as prior use.

SUBMITTER: Kronstrand R

PROVIDER: S-EPMC8446433 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:South Asia accounts for the majority of the world's suicide deaths, but typical psychiatric or surveillance-based research approaches are limited due to incomplete vital surveillance. Despite rich anthropological scholarship in the region, such work has not been used to address public health gaps in surveillance and nor inform prevention programs designed based on surveillance data. Our goal was to leverage useful strategies from both public health and anthropological approaches to provide rich narrative reconstructions of suicide events, told by family members or loved ones of the deceased, to further contextualize the circumstances of suicide. Specifically, we sought to untangle socio-cultural and structural patterns in suicide cases to better inform systems-level surveillance strategies and salient community-level suicide prevention opportunities. Using a mixed-methods psychological autopsy approach for cross-cultural research (MPAC) in both urban and rural Nepal, 39 suicide deaths were examined. MPAC was used to document antecedent events, characteristics of persons completing suicide, and perceived drivers of each suicide. Patterns across suicide cases include (1) lack of education (72% of cases); (2) life stressors such as poverty (54%), violence (61.1%), migrant labor (33% of men), and family disputes often resulting in isolation or shame (56.4%); (3) family histories of suicidal behavior (62%), with the majority involving an immediate family member; (4) gender differences: female suicides were attributed to hopeless situations, such as spousal abuse, with high degrees of social stigma. In contrast, male suicides were most commonly associated with drinking and resulted from internalized stigma, such as financial failure or an inability to provide for their family; (5) justifications for suicide were attributions to 'fate' and personality characteristics such as 'stubbornness' and 'egoism'; (5) power dynamics and available agency precluded some families from disputing the death as a suicide and also had implications for the condemnation or justification of particular suicides. Importantly, only 1 out of 3 men and 1 out of 6 women had any communication to family members about suicidal ideation prior to completion. Findings illustrate the importance of MPAC methods for capturing cultural narratives evoked after completed suicides, recognizing culturally salient warning signs, and identifying potential barriers to disclosure and justice seeking by families. These findings elucidate how suicide narratives are structured by family members and reveal public health opportunities for creating or supplementing mortality surveillance, intervening in higher risk populations such as survivors of suicide, and encouraging disclosure.

Project description:ObjectiveTo directly measure the fatal impact of coronavirus disease 2019 (covid-19) in an urban African population.DesignProspective systematic postmortem surveillance study.SettingZambia's largest tertiary care referral hospital.ParticipantsDeceased people of all ages at the University Teaching Hospital morgue in Lusaka, Zambia, enrolled within 48 hours of death.Main outcome measurePostmortem nasopharyngeal swabs were tested via reverse transcriptase quantitative polymerase chain reaction (PCR) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Deaths were stratified by covis-19 status, location, age, sex, and underlying risk factors.Results372 participants were enrolled between June and September 2020; PCR results were available for 364 (97.8%). SARS-CoV-2 was detected in 58/364 (15.9%) according to the recommended cycle threshold value of <40 and in 70/364 (19.2%) when expanded to any level of PCR detection. The median age at death among people with a positive test for SARS-CoV-2 was 48 (interquartile range 36-72) years, and 69% (n=48) were male. Most deaths in people with covid-19 (51/70; 73%) occurred in the community; none had been tested for SARS-CoV-2 before death. Among the 19/70 people who died in hospital, six were tested before death. Among the 52/70 people with data on symptoms, 44/52 had typical symptoms of covid-19 (cough, fever, shortness of breath), of whom only five were tested before death. Covid-19 was identified in seven children, only one of whom had been tested before death. The proportion of deaths with covid-19 increased with age, but 76% (n=53) of people who died were aged under 60 years. The five most common comorbidities among people who died with covid-19 were tuberculosis (22; 31%), hypertension (19; 27%), HIV/AIDS (16; 23%), alcohol misuse (12; 17%), and diabetes (9; 13%).ConclusionsContrary to expectations, deaths with covid-19 were common in Lusaka. Most occurred in the community, where testing capacity is lacking. However, few people who died at facilities were tested, despite presenting with typical symptoms of covid-19. Therefore, cases of covid-19 were under-reported because testing was rarely done not because covid-19 was rare. If these data are generalizable, the impact of covid-19 in Africa has been vastly underestimated.

Project description:BackgroundYoung people who have had contact with the youth justice system have an increased risk of dying from violence. Examining the context of violence-related deaths is essential in informing prevention strategies. We examined the circumstances and toxicology of violence-related deaths among young people who have had contact with the youth justice system in Queensland, Australia.MethodsThis data linkage study linked youth justice records from Queensland, Australia (30 June 1993-1 July 2014) on 48,670 young people to national death and coroner records (1 July 2000-1 January 2017). Circumstances and toxicology of deaths were coded from coroner's records. We calculated the incidence of violence-related deaths that were reported to a coroner. Fisher's exact tests were used to examine crude differences in the circumstances and toxicology of violence-related death, according to sex and Indigenous status.ResultsThere were 982 deaths reported to a coroner in the cohort. Of which, 36 (4%) were from violence-related causes (incidence: 6 per 100,000 person-years, 95% confidence interval: 4-8). People who died from violence were most frequently male (n = 28/36; 78%), and almost half were Indigenous (n = 16/36; 44%). The majority of violence-related deaths involved a weapon (n = 24/36; 67%), most commonly a knife (n = 17/36; 47%). Compared to men where the violent incident was most frequently preceded by an altercation (n = 12/28; 43%), for women it was frequently preceded by a relationship breakdown or argument (n < 5; p = 0.004). Substances most commonly present in toxicology reports were cannabis (n = 16/23; 70%) and alcohol (n = 15/23; 65%).ConclusionsTherapeutic alcohol and other drug programs, both in the community and detention, are likely important for reducing violence-related deaths among young people who have had contact with the youth justice system. The majority of violence-related deaths among women were in the context of intimate partner violence, indicating the urgent need for interventions that prevent intimate partner violence in this population. Diversion programs and increased investment in health and social services may reduce the overrepresentation of Indigenous people in the youth justice system and in violence-related deaths.

Project description:The use of designer benzodiazepines appears to be increasing in many countries, but data concerning blood concentrations are scarce, making interpretation of concentrations difficult. The aim of this study was to report blood concentrations of clonazolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam and phenazepam and to investigate the relationship between blood concentrations and impairment. The concentration data are from blood samples collected from living cases (apprehended drivers and other drug offences) and medico-legal autopsies. The blood samples were analysed for the seven designer benzodiazepines mentioned above by ultra high performance liquid chromatography-tandem mass spectrometry. Positive cases from between 1 June 2016 and 30 September 2019 were included. Blood concentrations and the conclusion from a clinical test of impairment (when available) are reported. The presented seven benzodiazepines were detected in a total of 575 cases, where 554 of these cases concerned apprehended drivers or other criminal offenders. The number of findings and the median (range) concentrations were as follows: clonazolam, n = 22, 0.0041 mg/L (0.0017-0.053 mg/L); diclazepam, n = 334, 0.0096 mg/L (0.0016-0.25 mg/L); etizolam, n = 40, 0.054 mg/L (0.015-0.30 mg/L); flualprazolam, n = 10, 0.0080 mg/L (0.0033-0.056 mg/L); flubromazepam, n = 5, 0.037 mg/L (0.0070-0.70 mg/L); flubromazolam, n = 20, 0.0056 mg/L (0.0004-0.036 mg/L); and phenazepam, n = 138, 0.022 mg/L (0.0018-0.85 mg/L). A designer benzodiazepine was the only drug detected with relevance for impairment in 25 of the 554 living cases. The physician concluded with impairment in 19 of the 25 cases. Most of the concentrations in these cases were relatively similar to or higher than the median reported concentrations. The most frequent other drugs detected were amphetamine, tetrahydrocannabinol, clonazepam and methamphetamine. The presented blood concentrations can be helpful with the interpretation of cases involving one or more of these seven benzodiazepines. The results indicate that concentrations commonly observed in forensic cases are associated with impairment.

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Circumstances, Postmortem Findings, Blood Concentrations and Metabolism in a Series of Methoxyacetylfentanyl-Related Deaths.

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