Baclofen-related deaths in Australia 2000-2022.

In Australia, the therapeutic indication of baclofen (oral tablets) is for the treatment of muscle spasm. Deaths related to baclofen have been reported, as well as misuse, dependence and self-poisoning. This national retrospective study aimed to investigate the number, characteristics, circumstances, and toxicology of baclofen-related deaths in Australia, 2000-2022. We identified 102 baclofen-related deaths, with a mean age of 45.6 years and 51 % being male. Circumstances of death were: intentional toxicity (54.9 %), unintentional toxicity (30.4 %), unintentional toxicity/disease (9.8 %), and accidental injury (4.9 %). Multiple sclerosis or spinal injury was documented in 15.7 % of cases, substance use problems in 43.1 % and specifically alcohol use problems in 38.2 %. Mental health problems were documented in 73.5 %, a previous self-harm or suicide attempt in 30.4 %, and chronic pain in 37.3 %. The median baclofen blood concentration for all cases was 3.10 mg/L (25th 0.70, 75th 8.10, range 0.04-110.00), unintentional toxicity 1.95 mg/L (25th 0.70, 75th 4.35, range 0.04-24.0), intentional toxicity 6.00 mg/L (25th 1.10, 75th 13.0, range 0.05-110.0). Concomitant substance use was seen in 93.8 %, with antidepressants (69.8 %) and benzodiazepines (64.6 %) most frequently detected. In conclusion, the 'typical' case was middle-aged, most dying due to intentional toxicity, and likely to have a history of mental health and substance use problems. We suggest caution is needed in prescribing baclofen given its potential to be used in intentional and non-intentional overdose.

Changes in the rates and characteristics of gamma hydroxybutyrate (GHB)-related death in Australia, 2001-2023.

INTRODUCTION: In recent years gamma hydroxybutyrate (GHB) use appears to have increased. This study aimed to determine: (i) population rates of GHB-related death in Australia, 2001-2021; and (ii) whether there have been changes in the characteristics of GHB-related death in Australia over the period 2001-2023. METHODS: Retrospective study of all Australian cases in which GHB was a mechanism contributory to death retrieved from the National Coronial Information System (n = 217). Joinpoint regression models were used to analyse trends in overall rates. RESULTS: Death rates were stable between 2001 and 2015 ('stable period') (annual percent change [APC] = 3.7) but showed marked acceleration between 2016 and 2021 ('accelerated period') (APC = 44.4). Circumstances of death were: unintentional toxicity (81.6%), intentional toxicity (5.1%), self-harm (6.0%), traumatic injury (7.4%). Compared to the stable period, later cases were slightly older (34.2 vs. 30.7 years, p < 0.05), less likely to be employed (odds ratio [OR] 0.4), but more likely to have substance use problems (OR 3.9), a history of injecting drug use (OR 3.5), mental health problems (OR 3.6), and to have present in their blood at toxicological screening opioids (OR 3.2) and hypnosedatives (OR 3.7). The median blood GHB concentration was 170 mg/L, (range 0-3210), which did not change significantly. There were no differences in major organ pathology, but the proportion with aspiration pneumonia declined (OR 0.4). DISCUSSION AND CONCLUSIONS: GHB-related death rates increased from 2016, accompanied by changes in case characteristics. In recent years GHB use appears to have extended to a population more likely to have substance use problems and use other respiratory depressants.

Neuropathology of deaths due to acute alcohol toxicity in Australia, 2011-2022.

BACKGROUND: A major alcohol-related harm is structural pathology affecting the brain. The study aimed to: 1. Determine the frequency and nature of neuropathology amongst cases of death due to acute alcohol toxicity; 2. Compare diagnoses of brain atrophy with pathology in other organs; 3. Determine the demographic, clinical and organ pathology correlates of brain atrophy. METHODS: Retrospective study of 500 cases of death attributed to acute alcohol toxicity in Australia, 2011-2022. Data on clinical characteristics, toxicology, neuropathology and other organ pathology were retrieved from police reports, autopsies, toxicology and coronial findings. RESULTS: Mean age was 49.5 years, 69.4 % were male, with alcohol use problems documented in 70.2 %. Brain atrophy was diagnosed in 60 cases (12.0 %), most commonly in the cerebellum (32 cases, 6.4 %). Atrophy at other sites was present in 37 (7.4 %). The presence of brain atrophy was lower than other major pathologies: cardiomegaly (32.6 %, p<.001), nephro/arteriosclerosis (30.2 %, p<.001), and chronic obstructive pulmonary disease (21.8 %, p<.001) but not hepatic cirrhosis (11.9 % p=1.0). Those diagnosed with atrophy were older (53.4v 49.0 years, p<.001), more likely to have documented alcohol problems (85.0v 68.2 %, Odds ratio: OR 2.53) and seizure history (10.0v 3.0 %, OR 2.92), to have cardiomegaly (43.3v 31.0 %, OR 1.90, COPD (48.3v 18.2 %, 3.57) and nephro/arteriosclerosis (50.0 v 27.4 %, OR 2.27). CONCLUSIONS: Despite the majority of cases having a history of alcohol problems, the level of neuropathology amongst cases of death due to acute alcohol toxicity was comparatively low.

A retrospective study of the characteristics and toxicology of cases of lysergic acid diethylamide (LSD)- and psilocybin-related death in Australia.

BACKGROUND AND AIMS: Lysergic acid diethylamide (LSD) and psilocybin are used as recreational drugs, and there is renewed interest in their clinical use. The current study aimed to (1) determine the circumstances of death and case characteristics of LSD- and psilocybin-related death in Australia, 2000-23; and (2) determine the toxicological profile and major autopsy findings of these cases. METHODS: This was a retrospective exploratory study of all cases of LSD- and psilocybin-related death in Australia, 2000-23, retrieved from the National Coronial Information System. RESULTS: A total of 43 cases were identified: 33 LSD and 10 psilocybin. The median ages were 24 years [interquartile range (IQR) = 13, range = 16-53] (LSD) and 26 years (IQR = 18.5, range = 20-58) (psilocybin), and fewer than five cases were female. The most common circumstance of death among both groups was traumatic accident (LSD 36.4%, psilocybin 40.0%). There were 12 cases of self-harm, all of which involved LSD, all by physical means. In a fifth, death was attributed to multiple drug toxicity (LSD 18.2%, psilocybin 20.0%). In one case, death was attributed solely to LSD toxicity, while in a further two cases death was attributed to a cardiovascular event following LSD consumption (one LSD only, one multiple drug toxicity). In four psilocybin cases, the cause of death was undetermined. The most common clinical presentation was severe agitation (LSD 27.3%, psilocybin 20.0%). Median blood concentrations were LSD 0.8 µg/l (IQR = 1.7, range = 0.1-3), psilocin 20 µg/l (IQR = 53.5, range = 6-83). LSD was the only drug present in 25.0% of LSD cases and psilocybin in 20.0% of psilocybin cases. Pre-existing organ pathology was uncommon. CONCLUSIONS: Lysergic acid diethylamide (LSD)- and psilocybin-related death in Australia from 2000 to 2023 was primarily due to traumatic injury, whether through accident or self-harm. Cases of acute toxic reactions that were attributed solely to LSD were rare.

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.

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.

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.

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.

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.