Poisoning Deaths Research Articles

Cardiovascular Disease in Acute Cocaine Compared to Acute Fentanyl Intoxication Deaths.

Cocaine is the most common stimulant drug that causes death in Connecticut. Unlike opioid intoxication deaths, which largely correlate with dose/concentration, cocaine deaths occur more idiosyncratically, with mechanisms of death often related to underlying cardiovascular disease. We examined 78 sole acute cocaine and 306 sole acute fentanyl intoxication deaths to assess their association with cardiovascular disease. In the cocaine cohort, 87% (68/78) had atherosclerotic and/or hypertensive cardiovascular disease while 40% (122/306) in the fentanyl cohort did. Cocaine was detected in 40% of all accidental drug intoxication deaths, 41% of all accidental drug intoxication deaths involving fentanyl, and 37% of all drug intoxication deaths involving heroin. The relatively low number of sole cocaine deaths compared to the much higher proportion of cocaine/opioid deaths may be explained by the synergistic effects encountered in many mixed drug intoxications, the contributory role of cardiovascular disease in sole cocaine deaths, and/or the increased prevalence and potency of fentanyl. The high number of sole cocaine deaths in which the decedents had co-existing heart disease compared to those from sole fentanyl deaths (P < 0.001) suggests that heart disease plays a mechanistic role in sole cocaine deaths, whereas the potency of fentanyl is the dominant mechanism in fentanyl deaths.

A nationwide Swedish retrospective study on poisoning deaths between the years 2000 and 2022.

Approximately 1% of Sweden's 90 000 annual deaths were reported caused by poisoning. In this study, we aim to describe this poisoning population's characteristics, autopsy frequency and results of toxicology testing. A national cohort study based on Swedish national registers. All deceased subjects older than 18 years with poisoning as the cause of death registered between 1 January 2000 and 31 December 2021 were included. Causes of death according to primary ICD-10 code were analysed along with the substances found in forensic chemistry testing. There were 27 057 poisonous deaths during the study periods 2 018 495 adult deaths. Subjects deceased due to poisoning had a median age of 53 years, and 18 838 (70%) were men. A private home was the most reported location of death (52%). In total, 23 260 (87%) did undergo some sort post-mortem examination. Drugs (synthetic narcotics, opioids, heroin) caused 12 448 (46%) deaths, and alcohols explained 9056 cases (33%). Positive toxicological tests were found in 22 550 (83%) of the subjects. The most common separate substances were ethanol, zopiclone and nordazepam. Poisoning caused 1.3% of Swedish deaths. Men in their 50s were the most common victims, and their deaths were often cause by synthetic narcotics, other opioids or alcohol. The autopsy frequency was lower than expected for poisonous deaths.

Decedents Found in Bathtubs.

We investigated deaths in bathtubs for criteria to assist in death certification. We reviewed 252 deaths in which the person was found dead in a bathtub/shower at home. We extracted cause, manner, age, clad or unclad, water in the bathtub, water running, and face submersion. Of the 252 deaths, heart disease was the leading cause of death (129), followed by intoxication (47), trauma (22), drowning (28), and other diseases (26). The manners of death were 155 natural, 64 accident, 30 suicide, and 3 homicides. All drowning fatalities involved the decedent having their face submerged. Intoxication and natural deaths had submersion of the face in 15% and 12% of deaths, respectively. For nondrowning causes of death, the majority were without face submersion. For natural deaths, the predominant circumstance was the individual discovered unclad with water in the bathtub and the face not submerged. Conversely, for suicides, the majority were found clad without water. A comprehensive investigation incorporating a scene examination, gathering of the medical and psychosocial history, and typically an autopsy is needed to certify the cause and manner of death. Face submersion alone is not diagnostic of a drowning and must be interpreted with the medical history and autopsy findings.

Etizolam and Irish drug poisoning deaths.

Etizolam and Irish drug poisoning deaths.

A five-year retrospective review of fatalities involving novel psychoactive substances in Southern Ireland

Introduction: Novel psychoactive substances (NPS) are rapidly emerging and being reformulated to evade legislative controls, creating unpredictability in drug markets and ineffective drug policies. Given that Ireland has the highest self-reported NPS use within Europe and literature regarding health risks is lacking, the National Advisory Committee on Drugs has advocated for the surveillance of regional trends. Objectives: To elucidate the demographic and autopsy findings of fatal cases involving NPS in Southern Ireland as compared to deaths involving traditional drugs of abuse (TDOA). Methods: Post-mortem reports from the Cork-Kerry region with positive toxicology for illicit substances between 2012-2016 were retrospectively analyzed to compare NPS and TDOA cases with respect to circumstances surrounding death, toxicological results, and pathological findings. Results: Between 2012-2016, there were 164 cases involving illicit substances in the Cork-Kerry region. NPS accounted for 17 (10.4%) cases, with an average annual mortality rate of 34.8 per 100,000 population. NPS contributed to the cause of death in 70.6% of cases where detected, compared to 43.5% for TDOA only. In both cohorts, fatal abusers were predominantly young males. Importantly, cases involving NPS showed a higher proportion of mono-drug intoxication and presentation to hospital prior to death. Autopsy findings were non-specific but commonly featured pulmonary congestion, aspiration, and cerebral oedema. Conclusion: NPS are detected in a small proportion of medicolegal autopsies but contribute significantly to acute intoxication deaths. This study highlights the need for effective drug monitoring and enforcement strategies, along with improved management of drug toxicities presenting to hospital.

Safer supply and political interference in medical practice: Alberta's Narcotics Transition Services

Across much of Canada, opioid poisoning deaths have been increasing due to a toxic, contaminated, and unpredictable drug supply. Multiple prescribed safer supply pilot projects are being implemented and evaluated in an attempt to save lives. In the province of Alberta, however, new regulations introduced in 2022 significantly constrain safer supply prescribing by banning the prescription, dispensing, and administration of safer supply outside of a very limited number of clinics. In this commentary, we review prescribed safer supply programs in Canada and outline how the Alberta Government's change in regulations conflict with emerging evidence and efforts by other jurisdictions to address the rising opioid poisoning deaths. We examine the development of these regulations and analyze how the Alberta government shaped and justified this restrictive policy. We conclude by identifying important lessons learned from the experience in Alberta for researchers, healthcare providers, and decisionmakers in other jurisdictions.

Stability and Volatility in the Contextual Predictors of Working-Age Mortality in the United States.

The contextual predictors of mortality in the United States are well documented, but the COVID-19 pandemic may have upended those associations. Informed by the social history of disease framework (SHDF), this study examined how the importance of county contexts on adult deaths from all causes, drug poisonings, and COVID-19-related causes fluctuated during the pandemic. Using 2018 to 2021 vital statistics data, for each quarter, we estimated associations between county-level deaths among adults ages 25 to 64 and prepandemic county-level contexts (economic conditions, racial-ethnic composition, population health profile, and physician supply). The pandemic significantly elevated the importance of county contexts-particularly median household income and counties' preexisting health profile-on all-cause and drug poisoning deaths. The elevated importance of household income may be long-lasting. Contextual inequalities in COVID-19-related deaths rose and then fell, as the SHDF predicts, but rose again along with socio-political disruptions. The findings support and extend the SHDF.

Differences in livor mortis in Wistar rats due to organophosphate induction and normal mortality: A randomized experimental study

Background: Pesticide intoxication, a significant global health issue, particularly in developing nations, is often caused by the most toxic pesticides, organophosphates. These substances activate the sympathetic and parasympathetic nervous systems, producing a characteristic livor mortis. It is a secondary sign of death that can be used to estimate the time and cause of death. Objective: This study aims to determine the difference in livor mortis due to organophosphate poisoning and ordinary death (decerebration) using Wistar rats.Methods: From March to April 2023, we conducted an experimental study with a posttest-only control group at the Laboratory of Animal Experiments, Faculty of Medicine, Sebelas Maret University. We used 32 male Wistar rats weighing 150-200 g, divided into control and test groups. The test group received organophosphate diazinon 1.16 ml through a nasogastric tube, while the control group was decerebrated. The data was processed with univariate analysis and an independent t-test.Results: There was a significant difference in the appearance and the persistence time of livor mortis between the control and test groups (p &lt; 0.05). The color of livor mortis in the control group was purplish blue, while in the test group, it was reddish to blackish blue. Most of our samples displayed a distribution of livor mortis in the abdominal and dorsal regions, with a some displaying an abdominal distribution only.Conclusion: Our study reveals significant differences in the appearance and persistence time, as well as the color and distribution of livor mortis between decerebrated and organophosphate-induced dead rats.

Detection of N-desethyl etonitazene in a drug checking sample: Chemical analysis and pharmacological characterization of a recent member of the 2-benzylbenzimidazole “nitazene” class

The emergence of 2-benzylbenzimidazole “nitazene” opioids is stirring up the recreational synthetic opioid market. Many nitazene analogues act as potent agonists at the µ‑opioid receptor (MOR), as demonstrated in various in vitro and in vivo studies. Severe intoxication and overdose deaths associated with nitazene analogues are increasingly being reported. Nitazene opioids are classified as a public health threat, stressing the need for close monitoring of new developments on the recreational drug market. This study reports on the detection of N-desethyl etonitazene in a sample handed in by a recreational drug user at a Swiss drug checking service in August 2023. The person bought the sample through an internet source where it was stated to contain isotonitazene. Chemical analyses were conducted to characterize the sample, i.e. nuclear magnetic resonance (NMR), capillary electrophoresis (CE), and high-resolution mass spectrometry (HRMS). The sample was additionally investigated using two different in vitro MOR activation assays. NMR and high-performance liquid chromatography (HPLC) coupled to HRMS confirmed the presence of N-desethyl etonitazene at a high purity and in the absence of isotonitazene and etonitazene. N-Desethyl nitazene analogues have been detected before as metabolites of isotonitazene and etonitazene. However, as first seen with N-desethyl isotonitazene, they are now emerging as standalone drugs. The applied bioassays demonstrated increased efficacy and approximately 6–9-fold higher potency of N-desethyl etonitazene at MOR compared to fentanyl. N-Desethyl etonitazene showed EC50 values of 3.35 nM and 0.500 nM in the β-arrestin 2 recruitment and Aequoscreen® assays, respectively. The opioid activity present in the collected sample was additionally evaluated using the bioassays and showed good overlap with the reference standard, in line with the analytical purity assessment. This demonstrates the potential of these bioassays to provide a rapid opioid activity assessment of authentic samples. The emergence of other N-desethyl nitazene analogues must be considered during forensic and clinical toxicology casework, to avoid misclassification of intake of such analogues as metabolites. Finally, drug checking services enable the close monitoring of market developments and trends and are of great value for early warning and harm reduction purposes.

Age, period, and cohort trends of substance poisoning, alcohol-related disease, and suicide deaths in Australia, 1980-2019.

Deaths due to substance poisoning, alcohol-related disease, and suicide pose a critical public health issue, and have been categorized as "deaths of despair" in the US. Whether these deaths represent a distinct phenomenon requires exploration, particularly in other countries. This retrospective observational study examines age-period-cohort trends of (combined and cause-specific) substance poisoning, alcohol-related disease, and suicide deaths among Australians aged ≥15-years that occurred between 1980 and 2019 and compares trends between males and females. Combined mortality rates were initially (1980-1999) relatively stable, reflecting a reduction in alcohol-related disease deaths offset by an increase in substance poisoning deaths. A decline (2000-2006) and subsequent increase (2007-2019) in combined rates were primarily attributable to corresponding changes in both substance poisoning and suicide deaths among males. Distinct age-period-cohort trends were observed between cause of death sub-types, with net drifts: increasing for male (net drift [95% CI]: 3.33 [2.84, 3.83]) and female (2.58 [2.18, 2.98]) substance poisoning deaths; decreasing among male alcohol-related disease (-1.46 [-1.75, -1.16]) and suicide deaths (-0.52[-0.69, -0.36]); and remaining relatively stable for female alcohol-related disease (-0.28 [-0.66, 0.09]) and suicide deaths (-0.25 [-0.52, 0.01]). Although combined age-specific trends were relatively stable over the study period, different and distinct patterns were observed within cause-specific deaths, challenging the notion that these causes of death represent a distinct epidemiological phenomenon. These data indicate a critical need to review the appropriateness of guidance for clinical practice, prevention strategies, and policy initiatives aimed at preventing future deaths.

The association between urban environment and drug poisoning deaths in Hong Kong

The association between urban environment and drug poisoning deaths in Hong Kong

Mephedrone concentrations in clinical intoxications and fatal cases: a systematic review.

Mephedrone, a ring-substituted synthetic cathinone derivative, gained popularity as a recreational drug in the late 2000s. Reports of fatalities related to mephedrone use have emerged with varying concentrations of blood mephedrone upon forensic investigations. This study aims to evaluate the existing literature on mephedrone concentrations in instances of clinical intoxication and fatal cases. We comprehensively searched electronic databases, including Web of Science, PubMed, Embase, and the Cochrane Library, from inception to July 26, 2023. We selected case reports or case series of mephedrone intoxication presented with individual blood mephedrone concentration. Patient demographics, clinical characteristics, blood mephedrone concentrations, and outcomes were extracted for analysis. 77 cases from 14 case reports and 6 case series were identified for review. There were 34 deaths and 43 non-fatal intoxication cases. The median patient's age was 24years (IQR: 10), and 91.4% were male. Forty-five of the 63 cases (71.4%) were reported with alcohol or other illicit drugs detected. The median blood mephedrone concentration was 0.37mg/L (IQR: 1.09mg/L). Death cases were older than non-fatal cases (median = 30 vs. 22years, p = 0.029). The median blood mephedrone concentration was higher in death cases (1.30mg/L vs. 0.12mg/L, p < 0.0001). Blood mephedrone concentration in dead patients is approximately 11 times higher than in non-fatal cases. This finding could serve as a stepping stone to the diagnosis of concentrations in clinical poisoning cases and deaths, especially in the treatment of poisoning patients. In more extensive prospective studies, further research is necessary to establish a standardized, real-time available methodology and validate the predictive value of mephedrone concentrations in the prognostic value of mephedrone concentrations.

Evaluation of the effect of clonazepam and its metabolites on the life cycle of Megaselia scalaris (Loew) (Diptera: Phoridae)

Fly colonization patterns and development are crucial in estimating the post-mortem interval (PMI) of decomposing corpses. Understanding the potential effects of xenobiotics on species development in cadaveric entomofauna is essential for accurate PMI estimation, given their presence in decomposing bodies. Benzodiazepines, commonly prescribed for their anxiolytic, hypnotic, and muscle relaxant effects, are of forensic interest due to their potential for abuse, dependence, intoxication, and overdose-related deaths. This study aimed to explore the effect of clonazepam and its metabolites on Megaselia scalaris, a species commonly used to estimate PMI, the alteration of which could impact the accuracy of said estimation. The S9 biotransformation fraction, an in vitro model consisting of an array of metabolic enzymes, was used to generate phase I and II metabolites for evaluating their effect on M. scalaris development, representing an innovative approach to this type of study. Megaselia scalaris larvae were reared in synthetic growth media under controlled conditions. The study compared different groups: control, clonazepam, and clonazepam with S9 fraction. Larvae were measured daily to determine growth rate, and clonazepam concentrations were analyzed using HPLC-DAD. Results showed that larvae grown in media containing clonazepam or clonazepam with S9 fraction developed faster than control larvae, reaching their pupal stage earlier. Growth rates were also altered in treated groups. In conclusion, the presence of clonazepam and its metabolites accelerated the life cycle of M. scalaris, potentially impacting the accuracy of PMI estimation. These findings underscore the importance of considering xenobiotics in forensic entomological studies for precise post-mortem interval determination.

Salidroside Inhibits α-Amanitin-Induced AML-12 Cell Apoptosis via the Regulation of PINK1/Parkin-Mediated Mitophagy and Mitochondrial Function.

Poisoning caused by the mushroom Amanita phalloides, due to the toxin α-amanitin, accounts for approximately 90% of food poisoning deaths in China with no specific antidotes. To investigate the role of salidroside (Sal) in α-amanitin (α-AMA)-induced mitophagy, mouse liver cells AML-12 were exposed to α-AMA in the presence of Sal or not. Intracellular reactive oxygen species (ROS) levels were measured using a ROS detection kit, mitochondrial activity was evaluated using a mitochondrial red fluorescent probe kit or JC-1 dye, and protein expression levels of PINK1, Parkin, LC3 II, P62, Bax, Bcl-2, Caspase 3, Cleaved-Caspase 3, PARP I, and Cleaved-PARP I were detected through Western blot. Results demonstrated that α-AMA led to increased intracellular ROS levels, cell apoptosis, and decreased mitochondrial membrane potential. Notably, expression levels of mitophagy-related proteins PINK1, Parkin, and LC3 increased significantly while the P62 protein expression decreased remarkably. Furthermore, Sal reversed the α-AMA-induced decrease in cell viability and mitochondrial membrane potential and increase in intracellular ROS level. In addition, Sal promoted expression levels of PINK1, Parkin, and LC3 II while suppressing the Bax/Bcl-2 ratio, Cleaved-Caspase 3, and Cleaved-PARP I as well as P62. The results above proved that salidroside alleviates α-AMA-induced mouse liver cells damage via promoting PINK1/Parkin-mediated mitophagy and reducing cell apoptosis.

Effective skin decontamination with RSDL® (reactive skin decontamination lotion kit) following dermal exposure to a Novichok class nerve agent

In recent years, various poisoning incidents have been reported, involving the alleged use of the so-called Novichok agents, resulting in their addition to the Schedule I list of the Organisation for the Prohibition of Chemical Warfare (OPCW). As the physicochemical properties of these agents are different from the ‘classical’ nerve agents, such as VX, research is needed to evaluate whether and to what extent existing countermeasures are effective. Here, we evaluated the therapeutic potential of RSDL® (Reactive Skin Decontamination Lotion Kit) for the neutralization of percutaneous toxicity caused by Novichok agents, both in vitro and in vivo. Experiments showed the three selected Novichok agents (A230, A232, A234) could be degraded by RSDL lotion, but at a different rate. The half-life of A234, in the presence of an excess of RSDL lotion, was 36 min, as compared to A230 (<5 min) and A232 (18 min). Following dermal exposure of guinea pigs to A234, application of the RSDL kit was highly effective in preventing intoxication, even when applied up until 30 min following exposure. Delayed use of the RSDL kit until the appearance of clinical signs of intoxication (3–4 h) was not able to prevent intoxication progression and deaths. This study determines RSDL decontamination as an effective treatment strategy for dermal exposure to the Novichok agent A234 and underscores the importance of early, forward use of skin decontamination, as rapidly as possible.

Fatal Intoxications with Zopiclone-A Cause for Concern?

Zopiclone, a controlled substance prescribed for insomnia, has become a common toxicological finding in forensic autopsy cases. This study investigated the role and extent of zopiclone use in fatal intoxications in Sweden. All forensic autopsy cases positive for zopiclone in femoral blood during 2012-2020 were selected. Among these cases, fatalities caused by intoxication according to the cause of death certificates issued by the forensic pathologist were identified. Intoxications where zopiclone contributed to the cause of death were included in the study. The Swedish Prescribed Drug Register was utilized to examine whether the included cases were prescribed zopiclone or not. In total 7320 fatal intoxications underwent a forensic autopsy during the study period, 573 of them were caused by zopiclone. Among the zopiclone fatalities, 87% (n = 494) had a prescription for zopiclone, and 8% (n = 43) were monointoxications. Most fatalities, 62% (n = 354) were suicides, and zopiclone was involved in about 17% (n = 354) of all intoxication suicides in Sweden. Women were significantly (p < 0.01) overrepresented in suicides with zopiclone, comprising 56% (n = 291) of fatalities. The median age was 55 years among zopiclone intoxications compared with 44 years amongst all fatal intoxications. This study demonstrates that the toxicity of zopiclone can be lethal both in combination with other substances and on its own. Most individuals dying in fatal zopiclone intoxications were prescribed zopiclone, which potentially indicates that a more restrictive prescribing rate could prevent future intoxication deaths, especially when caring for patients with an increased suicide risk.

A Series of 8 Illicit Fentanyl Intoxication Deaths in Infants and Toddlers.

We report 8 children younger than 2 years who died from acute illicit fentanyl intoxications in Connecticut between 2020 and 2022.The Connecticut Office of the Chief Medical Examiner (CT OCME) investigates all unexpected, violent, and suspicious deaths in Connecticut. The CT OCME's electronic database was searched for fentanyl deaths by age. All underwent autopsies and toxicology testing.The ages ranged from 28 days to 2 years (mean age, 12 months). The causes of death involved acute fentanyl intoxications with 1 having xylazine, 1 having para-fluorofentanyl, and 1 having cocaine and morphine. All the manners of death were certified as homicide. The postmortem fentanyl blood concentrations ranged from 0.40 to 46 ng/mL. Most of the children were found unresponsive after being put to sleep. Three were co-sleeping with adults (2 in bed; 1 on a recliner). There was a known history of parental/caregiver drug abuse in 7 of 8 of the fatalities.We summarize the key investigative, autopsy, and toxicological findings. As illicit fentanyl use increases, there is a potential for infant exposure and death. The investigation and certification of these deaths and the role of intentional administration versus inadvertent exposure due to caregiver neglect in the context of the certification of the manner of death are described.

Receipt of opioid use disorder treatments prior to fatal overdoses and comparison to no treatment in Connecticut, 2016–17

ObjectiveTo determine the relative risk of death following exposure to treatments for OUD compared to no treatment. MethodsIn this retrospective cohort study we compiled and merged state agency data on accidental and undetermined opioid overdose deaths in 2017 and exposures to OUD treatment in the prior six months to determine incidence rates following exposure to different treatment modalities. These rates were compared to the estimated incidence among those exposed to no treatment to determine relative risk of death for each treatment exposure. ResultsIncidence rates for opioid poisoning deaths for those exposed to treatment ranged from 6.06±1.40 per 1000 persons exposed to methadone to 17.36±3.22 per 1000 persons exposed to any non-medication treatment. The estimated incidence rate for those not exposed to treatment was 9.80±0.72 per 1000 persons. With no exposure to treatment as referent, exposure to methadone or buprenorphine reduced the relative risk by 38% or 34%, respectively; the relative risk of non-medication treatments was equal to or worse than no exposure to treatment (RR = 1.27–1.77). Principal conclusionsExposure to non-MOUD treatments provided no protection against fatal opioid poisoning whereas the relative risk was reduced following exposures to MOUD treatment, even if treatment was not continued. Population level efforts to reduce opioid overdose deaths need to focus on expanding access to agonist-based MOUD treatments and are unlikely to succeed if access to non-MOUD treatments is made more available.

Flawed reports can harm: the case of supervised consumption services in Alberta

Supervised consumption services have been scaled up within Canada and internationally as an ethical imperative in the context of a public health emergency. A large body of peer-reviewed evidence demonstrates that these services prevent poisoning deaths, reduce infectious disease transmission risk behaviour, and facilitate clients’ connections to other health and social services. In 2019, the Alberta government commissioned a review of the socioeconomic impacts of seven supervised consumption services in the province. The report is formatted to appear as an objective, scientifically credible evaluation of these services; however, it is fundamentally methodologically flawed, with a high risk of biases that critically undermine its authors’ assessment of the scientific evidence. The report’s findings have been used to justify decisions that jeopardize the health and well-being of people who use drugs both in Canada and internationally. Governments must ensure that future assessments of supervised consumption services and other public health measures to address drug poisoning deaths are scientifically sound and methodologically rigorous. Health policy must be based on the best available evidence, protect the right of structurally vulnerable populations to access healthcare, and not be contingent on favourable public opinion or prevailing political ideology.

The Management of Adult Male Prisoners with Substance Use Disorders Presenting with Suspected Internal Concealment of Illicit Drugs: Challenges, Clinical Implications, and Best Practice Response

Purpose: Internal concealment as a means of trafficking illicit drugs into prison is common and exposes internal concealers to risk of intoxication and overdose death. The management of internal drug concealment is a medical emergency that remains a challenge to healthcare professionals and custodial officers in prison settings