Aims
To (1) assess trends in the number and mortality rates of methamphetamine‐related death in Australia, 2009–15; (2) assess the characteristics and the cause, manner and circumstances of death; ...and (3) assess the blood methamphetamine concentrations and the presence of other drugs in methamphetamine‐related death.
Design
Analysis of cases of methamphetamine‐related death retrieved from the National Coronial Information System (NCIS).
Setting
Australia.
Cases
All cases in which methamphetamine was coded in the NCIS database as a mechanism contributing to death (n = 1649).
Measurements
Information was collected on cause and manner of death, demographics, location, circumstances of death and toxicology.
Findings
The mean age of cases was 36.9 years, and 78.4% were male. The crude mortality rate was 1.03 per 100 000. The rate increased significantly over time (P < 0.001), and at 2015 the mortality rate was 1.8 confidence interval (CI) = 1.2–2.4 times that of 2009. Deaths were due to accidental drug toxicity (43.2%), natural disease (22.3%), suicide (18.2%), other accident (14.9%) and homicide (1.5%). In 40.8% of cases, death occurred outside the major capital cities. The median blood methamphetamine concentration was 0.17 mg/l, and cases in which only methamphetamine was detected had higher concentrations than other cases (0.30 versus 0.15 mg/l, P < 0.001). The median blood methamphetamine concentration varied within a narrow range (0.15–0.20 mg/l) across manner of death. In the majority (82.8%) of cases, substances other than methamphetamine were detected, most frequently opioids (43.1%) and hypnosedatives (38.0%).
Conclusions
Methamphetamine death rates doubled in Australia from 2009 to 2015. While toxicity was the most frequent cause, natural disease, suicide and accident comprised more than half of deaths.
•First national study of cardiovascular disease of methamphetamine-related death.•Despite their young age, cardiovascular disease was common.•Cardiovascular disease was more common amongst males, and ...those aged >35yrs.•Significant cardiovascular disease was seen where it was not the cause of death.•With use increasing, cardiovascular disease will likely increase amongst users.
Methamphetamine dependence is a major public health problem. This study examined the nature, and extent, of cardiovascular disease amongst cases of methamphetamine-related death in Australia, 2009–2015.
Analysis of 894 cases of methamphetamine-related death with full autopsy reports retrieved from the National Coronial Information System.
The mean age was 37.9yrs (range 15–69yrs) and 78.5% were male. A quarter (26.3%) of cases had enlarged hearts and left ventricular hypertrophy was diagnosed in 18.9%. Severe coronary artery disease was present in 19.0%, the left coronary artery being the vessel most frequently stenosed (16.6%). Replacement fibrosis (evidence of earlier ischaemic events) in the heart muscle was observed in 19.8% of cases, and cardiomyopathy was diagnosed in 5.5%. Histological evidence of hypertension was observed in 32.7% of cases. With the exception of cardiomyopathy, equally common amongst both sexes, cardiovascular disease was more common amongst males, and those aged >35yrs. Clinically significant levels of cardiovascular disease were also observed amongst cases where the cause of death was not attributed to cardiovascular disease: cardiomegaly (19.3%), left ventricular hypertrophy (14.6%), severe coronary artery disease (9.4%), replacement fibrosis (14.4%), cardiomyopathy (3.3%).
Cardiovascular disease was highly prevalent, despite the relatively young age of cases. With methamphetamine use increasing rapidly in major regions, cardiovascular disease and cardiovascular-related death will likely increase amongst methamphetamine users.
Introduction: Synthetic cannabinoids are an emerging clinical and public health concern. The current study aimed to determine: (1) The characteristics and circumstances of death of all recorded cases ...of synthetic cannabinoid-related sudden or unnatural death in Australia, (2) The toxicology of cases and (3) Their major organ pathology.
Methods: Retrospective study of all cases in Australia in which synthetic cannabinoid use was a mechanism contributory to death (n = 55) retrieved from the National Coronial Information System (2000-2017). Information was collected on cause of death, demographics, drug use history, circumstances of death, toxicology and major organ pathology.
Results: The mean age was 37.2 years and 91.1% were male. Causes of death comprised of accidental toxicity (38.2%), accidental toxicity/cardiovascular disease (9.1%), natural disease (20.0%), suicide (10.9%) and traumatic accident (10.9%). The most common clinical presentation proximal to death was sudden collapse (25.5%). Cardiovascular disease was prominent: severe atherosclerosis (20.0%), myocardial replacement fibrosis (18.0%), cardiomegaly (12.0%). The most frequent synthetic cannabinoids were the indazolecarboxemides (61.8%), most commonly AB-CHMINACA (38.2%). The most frequent other substances were alcohol (34.5%) and Δ
9
-THC (23.6%).
Conclusions: AB-CHMINACA was the most commonly seen synthetic cannabinoid. There was a high representation of relatively older decedents and of older males in particular. While acute toxicity was the most common cause of death, cardiovascular disease was prominent.
Sudden cardiac death among children and young adults is a devastating event. We performed a prospective, population-based, clinical and genetic study of sudden cardiac death among children and young ...adults.
We prospectively collected clinical, demographic, and autopsy information on all cases of sudden cardiac death among children and young adults 1 to 35 years of age in Australia and New Zealand from 2010 through 2012. In cases that had no cause identified after a comprehensive autopsy that included toxicologic and histologic studies (unexplained sudden cardiac death), at least 59 cardiac genes were analyzed for a clinically relevant cardiac gene mutation.
A total of 490 cases of sudden cardiac death were identified. The annual incidence was 1.3 cases per 100,000 persons 1 to 35 years of age; 72% of the cases involved boys or young men. Persons 31 to 35 years of age had the highest incidence of sudden cardiac death (3.2 cases per 100,000 persons per year), and persons 16 to 20 years of age had the highest incidence of unexplained sudden cardiac death (0.8 cases per 100,000 persons per year). The most common explained causes of sudden cardiac death were coronary artery disease (24% of cases) and inherited cardiomyopathies (16% of cases). Unexplained sudden cardiac death (40% of cases) was the predominant finding among persons in all age groups, except for those 31 to 35 years of age, for whom coronary artery disease was the most common finding. Younger age and death at night were independently associated with unexplained sudden cardiac death as compared with explained sudden cardiac death. A clinically relevant cardiac gene mutation was identified in 31 of 113 cases (27%) of unexplained sudden cardiac death in which genetic testing was performed. During follow-up, a clinical diagnosis of an inherited cardiovascular disease was identified in 13% of the families in which an unexplained sudden cardiac death occurred.
The addition of genetic testing to autopsy investigation substantially increased the identification of a possible cause of sudden cardiac death among children and young adults. (Funded by the National Health and Medical Research Council of Australia and others.).
Postmortem genetic testing (molecular autopsy) for the common long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) genes reveals a pathogenic mutation in up to 30% ...of sudden unexplained death (SUD). The role of additional cardiac arrhythmia and cardiomyopathy genes in SUD is largely unknown.
The purpose of this study was to investigate the feasibility and outcomes of performing exome sequencing-based molecular autopsies in a cohort of consecutive SUD cases.
Autopsies performed from 2005 to 2009 were reviewed for SUD. Postmortem blood was collected, DNA was isolated, and whole exome sequencing was performed. Rare sequence variants in cardiac arrhythmia and cardiomyopathy genes were sought.
There were 50 SUD cases aged 1 to 40 years (mean 21.7 ± 12 years) in the 5-year period, with a male predominance of 1.9:1. The most common event at death was "sleep" (48%). Exome sequencing in a subgroup of 28 SUD cases revealed 3 rare variations in 3 SUD cases (10%; 2 from exome sequencing and 1 from previous Sanger sequencing) in the common LQTS genes: a splice site variation and a single base deletion in KCNH2, and a missense variation in KCNQ1. Six rare variations in an additional 25 common genes of cardiac arrhythmias and cardiomyopathies were identified in 6 SUD (21%).
Exome sequencing-based molecular autopsy is a useful strategy as part of the investigation of SUD cases. The findings further expand the role of the molecular autopsy in both identifying a cause of death in the decedent and evaluating at-risk family relatives.
All Australian cases of methamphetamine‐related suicide (2009–2015) retrieved from the National Coronial Information System were examined to determine crude mortality rates, characteristics and ...circumstances of death, and blood toxicology. There were 300 cases, 18.2% of all methamphetamine‐related deaths, and 1.6% of all completed suicides. The mean age was 33.1 years, and 77.0% were male. The crude mortality rate was 1.9 per 106, with males having a significantly higher rate than females (2.9 vs. 0.9 per 106). A quarter were known to have previous suicide attempts, and a history of psychosis was noted in 12.3%. In 40.7% of cases, witnesses described the decedent as having been agitated and/or aggressive immediately prior to the incident. The vast majority (85.3%), and of both sexes (males 87.0%, females 79.7%), used violent methods. Hanging (70.3%) was overwhelmingly the most frequent method among both males (70.1%) and females (71.0%). Prescription medications were frequently present: hypnosedatives (23.6%), antidepressants (19.5%), and antipsychotics (8.4%). Self‐poisoning cases were significantly more likely to have antidepressants (odds ratio: 4.2) and opioids (4.9) present, but less likely to have cannabis (0.3). Methamphetamine‐related suicide makes a large contribution to methamphetamine‐related death and represents a substantial clinical and public health problem.
ABSTRACT
Aims To examine the literature pertaining to the cardiovascular effects of methamphetamine and discuss the implications for methamphetamine users.
Methods Relevant literature was ...identified through comprehensive MEDLINE and EMBASE searches.
Findings and conclusions There is sufficient clinical and experimental evidence to suggest that methamphetamine can have adverse and potentially fatal effects on the cardiovascular system. The existing literature suggests that: (1) methamphetamine users are at elevated risk of cardiac pathology; (2) risk is not likely to be limited to the duration of their methamphetamine use, because of the chronic pathology associated with methamphetamine use; (3) the risk of cardiac pathology is greatest among chronic methamphetamine users; (4) pre‐existing cardiac pathology, due to methamphetamine use or other factors, increases the risk of an acute cardiac event; and (5) methamphetamine use is likely to exacerbate the risk of cardiac pathology from other causes, and may therefore lead to premature mortality.
Issues. The major physical and psychological health effects of methamphetamine use, and the factors associated with such harms. Approach. Comprehensive review. Key Findings. Physical harms reviewed ...included toxicity and mortality, cardiovascular cerebrovascular pathology, dependence and blood-borne virus transmission. Psychological harms include methamphetamine psychosis, depression, suicide, anxiety and violent behaviours. Implications. While high-profile health consequences, such as psychosis, are given prominence in the public debate, the negative sequelae extend far beyond this. This is a drug class that causes serious heart disease, has serious dependence liability and high rates of suicidal behaviours. Conclusion. The current public image of methamphetamine does not portray adequately the extensive, and in many cases insidious, harms caused. Darke S, Kaye S, McKetin R, Duflou J. Major physical and psychological harms of methamphetamine use. Drug Alcohol Rev 2008;27:253-262
Objective
The leading cause of epilepsy‐related premature mortality is sudden unexpected death in epilepsy (SUDEP). The cause of SUDEP remains unknown. To search for genetic risk factors in SUDEP ...cases, we performed an exome‐based analysis of rare variants.
Methods
Demographic and clinical information of 61 SUDEP cases were collected. Exome sequencing and rare variant collapsing analysis with 2,936 control exomes were performed to test for genes enriched with damaging variants. Additionally, cardiac arrhythmia, respiratory control, and epilepsy genes were screened for variants with frequency of <0.1% and predicted to be pathogenic with multiple in silico tools.
Results
The 61 SUDEP cases were categorized as definite SUDEP (n = 54), probable SUDEP (n = 5), and definite SUDEP plus (n = 2). We identified de novo mutations, previously reported pathogenic mutations, or candidate pathogenic variants in 28 of 61 (46%) cases. Four SUDEP cases (7%) had mutations in common genes responsible for the cardiac arrhythmia disease, long QT syndrome (LQTS). Nine cases (15%) had candidate pathogenic variants in dominant cardiac arrhythmia genes. Fifteen cases (25%) had mutations or candidate pathogenic variants in dominant epilepsy genes. No gene reached genome‐wide significance with rare variant collapsing analysis; however, DEPDC5 (p = 0.00015) and KCNH2 (p = 0.0037) were among the top 30 genes, genome‐wide.
Interpretation
A sizeable proportion of SUDEP cases have clinically relevant mutations in cardiac arrhythmia and epilepsy genes. In cases with an LQTS gene mutation, SUDEP may occur as a result of a predictable and preventable cause. Understanding the genetic basis of SUDEP may inform cascade testing of at‐risk family members. Ann Neurol 2016;79:522–534
Characteristics of death attributed solely to methamphetamine toxicity (MT, n = 93) by forensic pathologists were examined and compared to cases of multiple drug toxicity (MDT, n = 634). The mean age ...of MT cases was 36.7 years, and 86.0% were male. Strenuous activity was reported in 12.9%. The most common witness observations were: collapse (60.3%), difficulty in breathing (36.2%), and hyperthermia (27.6%). MT cases had higher blood methamphetamine (0.54 vs. 0.11 mg/L) and amphetamine (0.04 vs. 0.02 mg/L) concentrations and lower likelihoods for opioids (12.5% vs. 80.9%), hypnosedatives (27.3 vs. 60.7%), antidepressants (14.8 vs. 29.8%), and antipsychotics (9.1 vs. 19.7%). MT cases had significantly heavier hearts than MDT cases (423.4 vs. 385.8 g) and were more likely to have cardiomegaly (37.1 vs. 20.4%) and replacement fibrosis (25.7 vs. 14.5%). The clinical picture was of a sudden cardiac event in a middle‐aged man with a high methamphetamine concentration. Cardiovascular signs of heavy methamphetamine use are frequently seen.
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