Characteristics, toxicology and major organ pathology of deaths due to acute alcohol toxicity in Australia, 2011-2022.

INTRODUCTION: Acute alcohol toxicity is a significant component of alcohol-related mortality. The study aimed to: (i) determine the circumstances of death and characteristics of fatal alcohol toxicity cases, 2011-2022; (ii) determine their toxicological profile and major autopsy findings; and (iii) determine trends in population mortality rates. METHODS: Retrospective study of acute alcohol toxicity deaths in Australia, 2011-2022, retrieved from the National Coronial Information System. RESULTS: A total of 891 cases were identified, with a mean age of 49.2 years, 71.0% being male. Alcohol use problems were noted in 71.3%. In 57.5% death was attributed solely to acute alcohol toxicity, and combined acute alcohol toxicity/disease in 42.5%. There was evidence of sudden collapse in 24.9% of cases. The mean BAC was 0.331 g/100 mL (range 0.107-0.936), and spirits were the most commonly reported beverages (35.8%). Cases of combined toxicity/disease had significantly lower BACs than those attributed solely to alcohol toxicity (0.296 vs. 0.358 g/100 mL). Cardiomegaly was diagnosed in 32.5%, and severe coronary artery disease in 22.1%. Aspiration of vomitus was noted in 18.0%, and chronic obstructive pulmonary disease in 19.6%. Severe liver steatosis was present in 33.4% and 13.6% had cirrhosis. There was an average annual percentage increase in deaths of 7.90. DISCUSSION AND CONCLUSIONS: The 'typical' case was a long-standing, heavy spirits drinker. BACs showed enormous variation and no arbitrary concentration may be deemed lethal. Clinically significant disease was associated with death at a lower BAC and people with such disease may be at increased risk of alcohol poisoning.

Differences in heroin overdose deaths in Australia by age, 2020-2022: Disease and estimated survival times.

Background: The age of people who use illicit opioids has increased, with a clinical picture of accelerated ageing. The study aimed to determine, stratified by age: 1. The circumstances and characteristics of heroin-related toxicity deaths in Australia, 2020-2022; 2. The toxicological profile and autopsy findings; 3. The proportion of cases in which blood 6-acetyl morphine (6AM) was detected, as a measure of survival time. Methods: Retrospective study of 610 cases of fatal heroin-related drug toxicity in Australia, 2020-2022. Cases were stratified as: <30 years, 30-39 years, 40-49 years, ≥50 years. Results: Compared to the youngest group, those aged ≥50 years were more likely to have a history of chronic pain (12.4 v 3.3 %), to have their death attributed to combined drug toxicity/disease (20.1 v 3.3 %), and to have evidence of a sudden collapse (21.3 v 11.1 %). There were no differences in free morphine concentrations or glucuronide concentrations. Compared to the youngest group, however, the two older groups were significantly more likely to have 6AM present in blood, a proxy measure of a shorter survival time (52.0, 55.2 v 34.5 %). Compared to the youngest group, cases aged ≥50 years were more likely to be diagnosed with cardiomegaly (44.0 v 16.7 %), coronary artery disease (46.0 v 15.0 %), emphysema (35.0 v 5.1 %), hepatic steatosis (15.4 v 3.4 %), hepatic fibrosis (17.6 v 3.4 %), and cirrhosis (19.8 v 0.0 %). Conclusions: Older cases of heroin overdose had more extensive heart, lung, and liver disease, and appeared more likely to have shorter survival times.

A descriptive coronial study of heroin toxicity deaths in Australia, 2020-2022: Characteristics, toxicology and survival times.

BACKGROUND AND AIMS: Mortality rates among people who use heroin are estimated to be 15 times that of the general population. The study aimed to determine (1) the case characteristics and circumstances of death of heroin-related toxicity deaths in Australia, 2020-2022; (2) their toxicological profile and major autopsy findings; (3) the proportion of cases in which blood 6-acetyl morphine (6AM) was detected, as a proxy measure of survival times; and (4) compare 6AM positive and negative cases on toxicology, circumstances of death and acute clinical presentation. DESIGN: Retrospective study of heroin toxicity deaths in Australia, 2020-2022, retrieved from the National Coronial Information System. SETTING: This study was conducted Australia-wide. CASES: There were 610 cases of fatal heroin-related drug toxicity. MEASUREMENTS: Information was collected on characteristics, manner of death, toxicology and autopsy results. FINDINGS: The mean age was 42.6 years (range 18-73 years), 80.5% were male and 7.5% were enrolled in a drug treatment programme. The circumstances of death were as follows: unintentional drug toxicity (86.2%), combined unintentional drug toxicity/disease (11.3%) and intentional drug toxicity (2.5%). The median free morphine concentration was 0.17 mg/L (range 0.00-4.20 mg/L). Psychoactive drugs other than heroin were present in 95.2% (Confidence Interval 93.1%-96.8%), most commonly hypnosedatives (62.3%, 58.2%-66.4%) and psychostimulants (44.8%, 40.7%-49.1%). Major autopsy findings of clinical significance included acute bronchopneumonia (14.8%, 11.3%-18.8%), emphysema (16.9%, 13.2%-21.1%), cardiomegaly (30.1%, 12.7%-28.2%), coronary artery disease (27.4%, 23.0%-32.3%), coronary replacement fibrosis (13.4%, 10.1%-17.3%), hepatic cirrhosis (8.8%, 6.6%-12.2%) and renal fibrosis (10.3%, 7.3%-14.0%). In 47.0% (42.3%-51.2%), 6AM was present in blood. CONCLUSIONS: The 'typical' heroin overdose case in Australia from 2020 to 2022 was a male who injected heroin, aged in the 40s, not enrolled in a treatment programme and had used multiple drugs. In over half of cases, there had been a sufficient survival time for 6-acetyl morphine to have been metabolised, which may indicate times in excess of 20-30 min.

A case series of patients with filamin-C truncating variants attending a specialized cardiac genetic clinic.

Background: FLNC encodes for filamin-C, a protein expressed in Z-discs of cardiac and skeletal muscle, involved in intracellular signalling and mechanical stabilization. Variants can cause diverse phenotypes with skeletal (myofibrillar or distal myopathy) and/or cardiac (hypertrophic, restrictive, and arrhythmogenic cardiomyopathies) manifestations. Truncating variants have recently been implicated in arrhythmogenic cardiomyopathy (ACM) without skeletal disease. Case summary: Retrospective review of medical records, including cardiac investigations, was performed for families attending a specialized clinic with a FLNC truncating variant (FLNCtv). Variants were classified according to accepted variant interpretation criteria. Of seven families identified, six had primary cardiac phenotypes with one nonsense and five frameshift variants (nonsense-mediated decay competent) identified. One family had no cardiac phenotype, with a pathogenic variant (p.Arg2467Alafs*62) identified as secondary genetic finding. Of the six with cardiac phenotypes, proband age at diagnosis ranged 27-35 years (four females). Five families experienced sudden cardiac death (SCD) of a young relative (age range: 30-43 years), and one patient listed for cardiac transplant. Left ventricular (LV) ejection fraction ranged from 13 to 46%, with LV fibrosis (late gadolinium enhancement) on cardiac imaging or on postmortem histology seen in three families. Two families had one genotype-positive/phenotype-negative relative. Discussion: The FLNCtv causes a left-sided ACM phenotype with a high risk of severe cardiac outcomes including end-stage heart failure and SCD. Incomplete penetrance is observed with implications for reporting secondary genetic findings.

Characteristics and circumstances of volatile solvent misuse-related death in Australia, 2000-2021.

INTRODUCTION: Volatile solvent misuse-related death is associated with neuropsychiatric, cardiovascular, respiratory and renal pathology, as well as sudden death. The study aimed to determine: (1) the circumstances of death and case characteristics of volatile solvent misuse-related death in Australia, 2000-2021; (2) the toxicological profile of cases; and (3) the major autopsy findings. METHODS: Retrospective study of volatile solvent misuse-related death in Australia, 2000-2021 retrieved from the National Coronial Information System. FINDINGS: One hundred and sixty-four cases were identified, 79.9% male, mean age 26.5 years (8.5% aged 40 years or older). Circumstances of death were unintentional toxicity (61.0%), unintentional asphyxia (20.1%), intentional self-harm (12.2%) and traumatic accident (6.7%). The most commonly reported acute presentation prior to death was sudden collapse (22 of 47 witnessed events). The most frequently used solvents at the fatal incident were gas fuels (35.4%), gasoline (petrol) (19.5%) adhesives/paints (19.5%), aerosol propellants (12.8%), and volatile anaesthetics (12.8%). The most commonly detected volatile substances were butane (40.7%), toluene (29.6%), and propane (25.9%). Cannabis was present in 27.6% and alcohol in 24.6%. The prevalence of acute pneumonia amongst autopsied cases was low (5.8%) which, together with reports of sudden collapse, suggests that in many cases, death was extremely rapid. There were low levels of major organ pathology. CONCLUSIONS: While the average age of volatile solvent misuse-related death was in the mid-twenties, a substantial proportion occurred amongst people aged 40 years or older. Reflecting availability, gas fuels predominated. In many cases, death appeared to have been rapid.

Characteristics and circumstances of cocaine-related completed suicide in Australia, 2000-2021.

BACKGROUND: There has been a substantial global increase in cocaine use and associated harms. The current study aimed to: 1. Determine the case characteristics and circumstances of death of cocaine-related suicide in Australia 2000-2021; and 2. Determine the toxicological profiles of cases. METHODS: Retrospective study of cocaine-related death in Australia, 2000-2021, retrieved from the National Coronial Information System (NCIS). Suicide intent was based upon the NCIS code for "Intentional Self-harm", derived from case circumstances and coroners' conclusions. Sex comparisons were made for all major variables. RESULTS: A total of 157 cases were identified, 82.2% male, 79.5% employed, with a mean age of 32.3 years. Concerns for mental health were documented in 65.6%, a previous suicide attempt in 21.0%, a history of substance use treatment and/or negative consequences of substance use in 45.9% and injecting drug use in 14.6%. Manner of death amongst both sexes was predominantly by physical means (82.8%). Written intent was documented in 29.3%. Intense agitation prior to the incident was noted in 28.0% and conflict in 24.8%. The median blood cocaine concentration was 0.060 mg/L (range 0.007-5.500). Other drugs were present in 95.5%, most commonly alcohol (63.1%) with a median concentration of 0.140 g/100 ml. Psychostimulants other than cocaine were present in 31.2%. CONCLUSIONS: The 'typical' cocaine-related suicide case was a male, aged in their early thirties, who was highly likely to be employed. The majority of cases used physical means, and a substantial minority were highly agitated and engaged in conflict prior to the fatal incident.

Rates, characteristics and toxicology of cocaine-related deaths in Australia, 2000-2021.

AIMS: To (i) assess the population mortality rates of cocaine-related deaths in Australia, 2000 to 2021; (ii) determine the circumstances of death and case characteristics; and (iii) determine their toxicological profile. DESIGN: Retrospective study of cocaine-related deaths in Australia, 2000 to 2021, retrieved from the National Coronial Information System. SETTING: Australia-wide. CASES: A total of 884 cases, mean age = 33.8 (SD, 10.0) years and 86.5% (n = 765) male. MEASUREMENTS: Information was collected on characteristics, manner of death and toxicology. Only cases in which the presence of blood cocaine and/or metabolites were included. FINDINGS: Population rates did not significantly increase during 2001-2011 (annual percentage change [APC] = 1.5; CI, -3.2, 6.5), but from 2012, there was a marked acceleration (APC = 20.0, 95% CI, 15.5, 25.3). Circumstances of death were unintentional drug toxicity (70.7%, n = 625), intentional self-harm (17.8%, n = 157), traumatic accident (11.5%, n = 102). The proportion of cases constituted by unintentional toxicity declined across the study period (APC = -2.6; CI, -3.1, -2.1). There was a substantial decline in the proportion of cases with a history of injecting drug use (APC = -5.7; CI, -6.5, -4.9) and with a history of substance use problems (APC = -3.2; CI, -3.9, -2.5). Both cocaine (0.100 vs 0.050 mg/L, P < 0.001) and benzoylecgonine (0.590 vs 0.240 mg/L, P < 0.001) concentrations were higher amongst toxicity cases than in cases of death from traumatic injury. Cocaethylene was present in 26.4% (n = 233), levamisole in 18.6% (n = 164) and lignocaine in 11.5% (n = 102). Psychoactive drugs in addition to cocaine were present in 92.9% (n = 821), most commonly opioids (50.5%, n = 446), alcohol (47.1%, n = 416), hypnosedatives (43.2%, n = 382) and psychostimulants (30.3%, n = 268). There was a steady decline in the proportion of opioid positive cases (APC = -5.4; CI, -6.3, -4.5). CONCLUSIONS: There was a large increase in cocaine-related deaths across Australia from 2000 to 2021. This was accompanied by changes in case profiles, with histories of injecting drug use and substance use problems, as well as recent opioid use, becoming less prominent.

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating Variant.

BACKGROUND: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management.

Clinical characteristics of fatal cocaine toxicity in Australia, 2000-2021.

INTRODUCTION: With increased use, the number of cocaine-related deaths has increased. We aimed to determine: (i) the toxicological profile of cocaine, metabolites and adulterants amongst three groups of cocaine-related fatalities in which cocaine and/or metabolites were present in blood: (a) fatal toxicity, where cocaine only (CO) was present (n = 48), (b) multiple drug toxicity (MDT) where other drugs were present (n = 604), and (c) a comparison group of death from traumatic injury (TI, n = 232); (ii) the acute clinical presentation by group; and (iii) cardiovascular disease by group. METHODS: Retrospective study of cocaine-related deaths in Australia, 2000-2021, from the National Coronial Information System. RESULTS: The parent drug cocaine was significantly more common, and had a higher median concentration, amongst the CO group (97.9%, 1.550 mg/L) than the MDT (68.9%, 0.09 mg/L) and TI (70.7%, 0.05 mg/L) groups respectively. Similarly large ratios between CO, MDT and TI were seen for benzoylecgonine (2.100, 0.510, 0.240 mg/L), methylecgonine (1.350, 0.140, 0.070 mg/L), lignocaine (1.200, 0.200, 0.150 mg/L) and levamisole (0.230, 0.045, 0.025 mg/L). The two toxicity groups had significantly higher proportions than the TI group for reports of sudden collapse, seizure, acute psychosis, hyperthermia and vomiting. In addition, CO had higher proportions than MDT and TI of sudden collapse. CO had significantly higher proportions of cardiomegaly and coronary artery disease than the TI group. DISCUSSION AND CONCLUSIONS: Compared to MDT and TI cases, CO cases had higher cocaine concentrations, higher concentrations of adulterants, higher levels of cardiovascular disease and were more likely to suddenly collapse.

Characteristics of fatal tapentadol-related toxicity in Australia.

INTRODUCTION: Tapentadol is a centrally acting opioid analgesic prescribed for the treatment of moderate to severe pain. The study aimed to determine the characteristics of Australian toxicity deaths related to tapentadol. METHODS: All cases in which tapentadol use was coded contributory to death (n = 159) were retrieved from the National Coronial Information System (1 July 2000-31 December 2020). RESULTS: The mean age was 48.5 (18-81) and 56% were female. Documented histories of problems with chronic pain (66%), mental health (60.4%), substance use (44%) and injecting drug use (23.3%) were common. The majority of deaths were deemed unintentional (76.1%) and in 18.9% pre-existing disease was co-contributory. The median peripheral blood tapentadol concentration was 1.00 mg L-1 (0.02-47.00), and the median aortic concentration was 2.05 mg L-1 (0.10-30.00). In all cases, psychoactive drugs other than tapentadol were also detected, most commonly antidepressants (72.3%), opioids (66.7%), hypnosedatives (64.2%) and gabapentinoids (43.4%). Of cases where autopsies were conducted, 27.7% were diagnosed with cardiomegaly and 18.5% with severe coronary artery stenosis. Pulmonary oedema (68.1%), aspiration of vomitus (39.5%) and acute pneumonia (26.9%) were common. DISCUSSION AND CONCLUSIONS: The typical tapentadol-related toxicity death involved unintentional death in the presence of multiple drugs, although a notable minority were intentional self-harm. Multiple morbidities were common. The identification and characteristics of these cases indicate that the adverse event profile of tapentadol needs to be considered in the setting of polypharmacy.

Characteristics of fatal 'novel' synthetic opioid toxicity in Australia.

BACKGROUND: Aims: To determine 1. The characteristics of all recorded cases of fatal drug poisoning involving novel synthetic opioids (NSOs) in Australia; 2. The toxicology of cases; and 3. The major autopsy findings. METHODS: Review of all fatal poisonings related to NSOs in Australia 2000-2021 identified in the National Coronial Information System. RESULTS: Thirty-one cases were identified, 96.8% due to unintentional drug toxicity. The mean age was 31.9 years and 87.1% were male. Only six were aged over forty. A history of substance use problems was documented in 80.6% and 58.1% had a history of injecting drug use. In 32.3% the final route of administration of a NSO was by non-injecting routes of administration. Ten NSOs were identified. Fentanyl analogues were present in 67.2%, most commonly furanylfenatyl (19.4%). Other NSO types were present in 39.7%, most commonly U-47700 (35.5%). Substances other than NSOs were present in 90.3%, most commonly benzodiazepines (67.7%) and other opioids (51.6%). A CNS depressant in addition to NSOs was present in 90.3%, and a new psychoactive substance other than a NSO in 25.8%. Pulmonary oedema was diagnosed in 82.6%, aspiration of vomitus in 30.4%, and acute bronchopneumonia in 17.4%. CONCLUSIONS: Ten NSOs were identified. Case characteristics suggest a younger cohort whose profile is more typical of use of other NPS than of the established opioids. A large proportion used NSOs by non-injecting routes of administration.

Characteristics of fatal 'novel' benzodiazepine toxicity in Australia.

INTRODUCTION: The study aimed to determine: 1. The characteristics of all recorded cases of fatal drug poisoning involving 'novel' benzodiazepines (NBZDs) in Australia; 2. The toxicology of cases; and 3. The major autopsy findings. METHODS: Retrospective study of all deaths due to drug toxicity in Australia in which NBZDs were present in blood toxicology, retrieved from the National Coronial Information System (2000-2021). Information was collected on case characteristics, toxicology and major organ pathology. RESULTS: A total of 40 cases were identified, the first occurring in 2015, with a median age of 26.5 years and 87.5% being male. Death was due to accidental toxicity in 92.5% of cases. There were extensive histories of substance use problems (80.0%) and mental health problems (32.5%). Etizolam was the most common NBZD (87.5%), followed by flubromazolam (15.0%), with other NBZDs detected in 20.0% (delorazepam, diclazepam, flualprazolam, flubromazepam, lormetazepam). Multiple NBZDs were present in 27.5%. Other drugs were present in 97.5%, most commonly opioids (70.0%), registered benzodiazepines (62.5%), psychostimulants (45.0%) and gabapentinoids (32.5%). A CNS depressant other than a NBZD was detected in 95.0% (n = 38). Autopsies were conducted and available for 30 cases, with pulmonary oedema (76.7%, n = 23), aspiration of vomitus (46.7%, n = 14) and acute bronchopneumonia (36.7%, n = 11) the most common diagnoses. CONCLUSIONS: The 'typical' NBZD-related death was a young male who died due to accidental toxicity. Deaths most frequently involved etizolam and multiple substances, particularly depressants.

Characteristics of fatal gabapentinoid-related poisoning in Australia, 2000-2020.

INTRODUCTION: Gabapentinoids are centrally active GABA agonists whose use has increased substantially in the past decade. The current study aimed to provide a comprehensive clinical profile of a national case series of fatal poisonings related to gabapentinoids. METHODS: Retrospective study of all deaths due to drug toxicity in Australia in which gabapentinoids were a contributory mechanism, retrieved from the National Coronial Information System (2000-2020). Information was collected on case characteristics, toxicology and major organ pathology. RESULTS: A total of 887 cases were identified, with a mean age of 45.7 years and 55.2% being male. Death was due to accidental toxicity in 81.3% of cases and intentional in 18.7%. Pre-existing disease was co-contributory to drug toxicity in 19.5%. Pregabalin was present in 92.9% of cases, with a median blood concentration of 7.6 mg/L (range 0.1-850.0 mg/L). Gabapentin was present in 7.2%, with a median blood concentration of 9.5 mg/L (range 0.5-1940.0 mg/L). Both pregabalin and gabapentin were present in five cases. No other gabapentinoids were detected. Drugs other than gabapentinoids were present in 99.8%, most frequently opioids (90.1%), hypnosedatives (76.9%) and antidepressants (60.5%). A body mass index in the obese range was seen in 45.4%. Clinically significant pre-existing disease was common, notably cardiomegaly (24.9%), emphysema (20.2%), nephrosclerosis (18.7%) and severe hepatic steatosis (11.7%). CONCLUSIONS: The concomitant use of other drugs was close to universal, with CNS depressants predominating. Mental health problems, chronic pain and substance misuse were prominent.

'Synthetic cannabis': A dangerous misnomer.

The term 'synthetic cannabis' has been widely used in public discourse to refer to a group of cannabinoid receptor agonists. In this paper we detail the characteristics of these drugs, and present the case that the term is a misnomer. We describe the pharmacodynamics of these drugs, their epidemiology, mechanisms of action, physiological effects and how these differ substantially from delta-9-tetrahydrocannabinol (THC). We argue that not only is the term a misnomer, but it is one with negative clinical and public health implications. Rather, the substances referred to as 'synthetic cannabis' in public discourse should instead be referred to consistently as synthetic cannabinoid receptor agonists (SCRAs), a drug class distinct from plant-derived cannabinoids. SCRAs have greater potency and efficacy, and psychostimulant-like properties. While such terminology may be used in the scientific community, it is not widely used amongst the media, general public, people who use these drugs or may potentially do so. A new terminology has the potential to reduce the confusion and harms that result from the misnomer 'synthetic cannabis'. The constant evolution of this distinct drug class necessitates a range of distinct policy responses relating to terminology, harm reduction, epidemiology, treatment, and legal status.

Global approaches to cardiogenetic evaluation after sudden cardiac death in the young: A survey among health care professionals.

BACKGROUND: Thorough investigation of sudden cardiac death (SCD) in those aged 1-40 years commonly reveals a heritable cause, yet access to postmortem genetic testing is variable. OBJECTIVE: The purpose of this study was to explore practices of postmortem genetic testing and attitudes of health care professionals worldwide. METHODS: A survey was administered among health care professionals recruited through professional associations, social media, and networks of researchers. Topics included practices around postmortem genetic testing, level of confidence in health care professionals' ability, and attitudes toward postmortem genetic testing practices. RESULTS: There were 112 respondents, with 93% from North America, Europe, and Australia/New Zealand, and 7% from South America, Asia and Africa. Only 30% reported autopsy as mandatory, and overall practices were largely case by case and not standardized. North American respondents (87%) more often perceived practices as ineffective compared to those from Europe (58%) and Australia/New Zealand (48%; P = .002). Where a heritable cause is suspected, 69% considered postmortem genetic testing and 61% offered genetic counseling to surviving family members. Financial resources varied widely. Half of participants believed practices in their countries perpetuated health inequalities. CONCLUSION: Postmortem genetic testing is not consistently available in the investigation of young SCD despite being a recommendation in international guidelines. Access to postmortem genetic testing, which is critical in ascertaining a cause of death in many cases, must be guided by well-resourced, multidisciplinary teams.

Characteristics and circumstances of death related to the self-administration of ketamine.

BACKGROUND AND AIMS: Ketamine is used for anaesthesia, sedation and the treatment of mood disorders, but is also widely used for non-medical purposes. This study aimed to: (1) determine the characteristics and circumstances of all recorded cases of self-administered ketamine-related death in Australia, 2000-19 and (2) determine the toxicology and major organ pathology of cases. DESIGN: Retrospective study of all Australian cases in which self-administered ketamine was a mechanism contributory to death, retrieved from the National Coronial Information System. SETTING: Australia-wide. CASES: Sixty-eight cases, with a mean age of 35.2 years (standard deviation = 11.5, range = 16-63), 76.5% male. MEASUREMENTS: Information was collected on cause of death, demographics, circumstances of death, toxicology and major organ pathology. FINDINGS: Death was attributed to toxicity in 82.3% of cases (accidental, 58.8%; deliberate, 23.5%), suicide by violent means (8.8%) and traumatic accident (8.8%). In six cases the decedent had been prescribed ketamine. In 32.4% the final route of ketamine administration was by injection. The fatal incident predominantly occurred in a private environment (72.1%). Ketamine was present in the blood of 90.1% and other biomarkers in the remainder. The median blood ketamine concentration was 0.2 mg/l (0.02-6.9 mg/l). Other drugs were detected in 95.5% of cases: opioids (59.1%), hypnosedatives (57.6%), psychostimulants (50.0%), alcohol (27.3%), Δ-9-tetrahydrocannabinol (18.2%), antidepressants (28.8%) and antipsychotics (9.1%). Pulmonary oedema was present in 82.2% of cases that underwent autopsy and pneumonia in 26.7%. CONCLUSIONS: The typical case of self-administered ketamine-related death in Australia, 2000-19, was a male in his mid-30s who had used multiple drugs, with the fatal incident most commonly occurring in a private setting. Death due to accidental drug toxicity was the most common manner of death, but suicide was highly prevalent.

Characteristics and circumstances of death related to buprenorphine toxicity in Australia.

BACKGROUND: Buprenorphine is a semi-synthetic opioid used in the treatment of opioid dependence and chronic pain. The current study aimed to determine the characteristics and circumstances of all recorded cases of buprenorphine-related toxicity death in Australia; determine toxicology and organ pathology; and compare these profiles to cases of death due to buprenorphine-related traumatic injury. METHODS: All cases of buprenorphine-related drug toxicity death were retrieved from the National Coronial Information System (2000-2019), as were all cases of buprenorphine-related traumatic injury. Information was collected on cause of death, case characteristics, toxicology and major organ pathology. RESULTS: A total of 314 cases of drug toxicity and 55 of traumatic injury were identified. Toxicity cases were significantly older (40.5 v 36.1 years), more likely to have a history of chronic pain (OR 2.95), less likely to have a history of injecting drug use (OR 0.09), but more likely to have injected buprenorphine proximal to death (OR 4.90). There were no group differences in buprenorphine or norbuprenorphine toxicology. Toxicity cases were more likely to have hypnosedatives (OR 2.08) and other opioids (OR 4.69) present, but less likely to have psychostimulants (OR 0.26) and THC (OR 0.45). Toxicity cases were more likely to be obese (OR 4.05), have pre-existing cardiovascular disease (OR 4.02) and heavier hearts (412.1 v 355.2 g). CONCLUSIONS: Buprenorphine-related toxicity death cases differed from trauma deaths in their characteristics, toxicology and disease. Fatal buprenorphine toxicity is associated with older age, concurrent use of depressants and cardiovascular disease.

Prevalence and Characteristics Associated with Chronic Noncancer Pain in Suicide Decedents: A National Study.

OBJECTIVE: The aims were to estimate the prevalence of CNCP in suicide decedents, and compare sociodemographic and clinical characteristics of people who die by suicide (i) with and without a history of CNCP and (ii) among decedents with CNCP who are younger (<65 years) and older (65 + years). METHOD: We examined all closed cases of intentional deaths in Australia in 2014, utilizing the National Coronial Information System. RESULTS: We identified 2,590 closed cases of intentional deaths in Australia in 2014 in decedents over 18 years of age. CNCP was identified in 14.6% of cases. Decedents with CNCP were more likely to be older, have more mental health and physical health problems, and fewer relationship problems, and were more likely to die by poisoning from drugs, compared with decedents without CNCP. Comparisons of older and younger decedents with CNCP found that compared to younger (<65 years) decedents with CNCP, older decedents (65 + years) were less likely to have mental health problems. CONCLUSIONS: This is the first national study to examine the characteristics of suicide deaths with a focus on people with CNCP. Primary care physicians should be aware of the increased risk for suicide in people living with CNCP, and it may be useful for clinicians to screen for CNCP among those presenting with suicidal behaviors.