Investigating opioid-related fatalities in southern Sweden: contact with care-providing authorities and comparison of substances.

BACKGROUND: Opioid-related deaths have increased in Western countries over recent decades. Despite numerous studies investigating opioid-related mortality, only a few have focused on the lives of the deceased individuals prior to their deaths, specifically regarding contact with care-providing authorities such as health, social and correctional services. Furthermore, a change has been noted in the last two decades as to which opioids cause most deaths, from heroin to prescription opioids. However, studies comparing fatalities caused by different substances are rare. The aim of this study was to investigate contact with care-providing authorities during the year prior to death among individuals who died as a result of opioid intoxication and to analyse differences relating to which opioids caused their deaths. METHODS: The study is based on retrospective register data and includes 180 individuals with a history of illicit drug use, who died from opioid intoxication in Skåne, Sweden, between 1 January 2012 to 31 December 2013 and 1 July 2014 to 30 June 2016. Intoxications caused by heroin, methadone, buprenorphine and fentanyl were included. Data were collected from the National Board of Forensic Medicine, regional health care services, municipal social services and the Prison and Probation Service. Statistical testing was performed using Pearson's chi-square test, Fisher's exact test and the Mann-Whitney U test to analyse group differences. RESULTS: A total of 89% of the deceased individuals had been in contact with one or more of the care-providing authorities during the year prior to death; 75% had been in contact with health care, 69% with the social services, 28% with the Prison and Probation Service, and 23% had been enrolled in opioid substitution treatment at some point during their final year of life. Few differences appeared between the substance groups with regard to which opioid contributed to the death. In addition to opioids, sedatives were present in more than 80% of the cases. Individuals whose deaths were buprenorphine-related had been in contact with the social services to a significantly lesser extent during the year prior to death. CONCLUSIONS: The studied population is characterised by extensive contact with care-providing authorities, thus providing numerous opportunities for authorities to reach this group with preventive and other interventions. Few differences emerged between groups with regard to which opioid had contributed to the death.

Prediction of psychiatric comorbidity on premature death in a cohort of patients with substance use disorders: a 42-year follow-up.

BACKGROUND: We need to better understand how the use of different substances and psychiatric comorbidity influence premature death generally and cause-specific death by overdose, intoxication and somatic disorders in people with substance use disorders. METHOD: A cohort of 1405 patients consecutively admitted to a Swedish detoxification unit for substance use disorders in 1970-1995 was followed-up for 42 years. Substances were identified by toxicological analyses. Mortality figures were obtained from a national registry. Causes of death were diagnosed by forensic autopsy in 594 patients deceased by 2012. Predictions were calculated by competing risks analysis. RESULTS: Forty-two per cent of the cohort died during follow-up; more men than women (46.3% vs 30.4%). The standardised mortality ratio (SMR) was calculated as the ratio of observed deaths in males and females in specific age groups in the cohort versus expected deaths in corresponding groups in the general population. SMR was 5.68 for men (CI 95%; 5.04-6.11) and 4.98 (CI 95%; 4.08-5.88) for women. The crude mortality rate (number of deaths divided by number of person observation years) was 2.28% for men and 1.87% for women. Opiates predicted increased risk of premature death while amphetamine and cannabis predicted lower risk. Comorbid psychiatric disorders were identified in 378 cases and personality disorders in 763 cases. Primary psychoses or mood/depression and anxiety disorders predicted a higher risk of premature mortality. Death by overdose was predicted by male gender, younger age at admission to substance treatment, opiate use, and comorbid depression and anxiety syndromes. Cannabis and amphetamine use predicted a lower risk of overdose. Death by intoxication was predicted by male gender, use of sedatives/hypnotics or alcohol/mixed substances, primary psychoses and depression/anxiety syndromes. Premature death by somatic disorder was predicted by male gender and alcohol/mixed abuse. CONCLUSION: Psychiatric comorbid disorders were important risk factors for premature drug-related death. Early identification of these factors may be life-saving in the treatment of patients with substance use disorders.

Sudden cardiac death among the young in Sweden from 2000 to 2010: an autopsy-based study.

AIMS: To study the incidence and aetiology of sudden cardiac death (SCD) in 1- to 35-year-olds in Sweden from 2000 to 2010. METHODS AND RESULTS: We used the database of the Swedish National Board of Forensic Medicine and the Swedish Cause of Death Registry and identified SCD cases by review of forensic files and death certificates. We identified 552 individuals with SCD in 1- to 35-year-olds; 156 (28%) were women. In 393 (71%), a forensic autopsy had been performed; in 131 (24%), a clinical autopsy had been performed; in 28 (5%) with no autopsy, a cardiac disease was diagnosed before death. The incidence of SCD per 100 000 person-years was 1.3 in 1- to 35-year-olds and 1.8 in 15- to 35-year-olds. In women, the incidence rates yearly decreased during the study period by 11% (95% confidence interval 6.6-14.2). The most common aetiology in 1- to 35-year-olds was sudden arrhythmic death syndrome (31%) and coronary artery disease (15%). In cases with forensic autopsy, death occurred during daily activity (48%), sleep (38%), and physical activity (14%); death was unwitnessed in 60%. Co-morbidity in 15- to 35-year-olds, e.g. psychiatric disorder, obesity, or diabetes, was present in 93/340 (27%) (73 men). CONCLUSION: The incidence of SCD among 1- to 35-year-olds in Sweden during 2000-10 was 1.3 per 100 000 person-years (28% women); incidence was decreasing in women. Sudden arrhythmic death syndrome was the most common diagnosis. Co-morbidity such as psychiatric disorders and obesity was common among men.

Genetic screening in sudden cardiac death in the young can save future lives.

BACKGROUND: Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds. METHODS AND RESULTS: From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40%). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT). CONCLUSION: Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death.

Substance abuse and psychiatric co-morbidity as predictors of premature mortality in Swedish drug abusers: a prospective longitudinal study 1970-2006.

BACKGROUND: Few longitudinal cohort studies have focused on the impact of substances abused and psychiatric disorders on premature mortality. The aim of the present study was to identify predictors of increased risk of drug related death and non drug related death in substance abusers of opiates, stimulants, cannabis, sedatives/hypnotics, hallucinogens and alcohol over several decades. METHODS: Follow-up study of a consecutive cohort of 561 substance abusers, admitted to a detoxification unit January 1970 to February 1978 in southern Sweden, and followed up in 2006. Demographic and clinical data, substance diagnoses and three groups of psychiatric diagnoses were identified at first admission. Causes of death were coded according to ICD-10 and classified as drug related deaths or non drug related deaths. To identify the incidence of some probable risk factors of drug related premature death, the data were subjected to a competing risks Cox regression analysis. RESULTS: Of 561 patients in the cohort, 11 individuals had either emigrated or could not be located, and 204/561 patients (36.4%) were deceased by 2006. The cumulative risk of drug related death increased more in the first 15 years and leveled out later on when non drug related causes of death had a similar incidence. In the final model, male gender, regular use of opiates or barbiturates at first admission, and neurosis were associated with an increased risk of drug related premature death, while cannabis use and psychosis were associated with a decreased risk. Neurosis, mainly depression and/or anxiety disorders, predicted drug related premature death while chronic psychosis and personality disorders did not. Chronic alcohol addiction was associated with increased risk of non drug related death. CONCLUSIONS: The cohort of drug abusers had an increased risk of premature death to the age of 69. Drug related premature death was predicted by male gender, the use of opiates or barbiturates and depression and anxiety disorders at first admission. The predicted cumulative incidence of drug related death was significantly higher in opiate and barbiturate abusers over the observed period of 37 years, while stimulant abuse did not have any impact. Alcohol contributed to non drug related death.

Exercise related sudden cardiac death (SCD) in the young - Pre-mortal characterization of a Swedish nationwide cohort, showing a decline in SCD among athletes.

AIMS: To study the frequency, etiology, and premortal abnormalities in exercise-related sudden cardiac death (SCD) in the young in Sweden. METHODS: All subjects with SCD in 10-35-year olds in Sweden during 2000-10, were included (n = 514). Information about each case was retrieved from death certifications, autopsy- and medical records. The number of SCD in athletes was compared to national figures from 1992-99. RESULTS: Exercise-related SCD occurred in 12% (62/514) of the SCD-population, a majority being men (56/62; 90%). Cardiopulmonary resuscitation (CPR) was started in 87% (54/62). In total, 48% (30/62), had a cardiac diagnosis, symptoms, family history and/or ECG-changes, before the fatal event. The most prevalent autopsy diagnosis was sudden arrhythmic death syndrome (15/62; 24%). The frequency of hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) was significantly higher in exercise-related SCD compared to non-exertional SCD. Exercise-related SCD was more common in athletes (21/29) than in non-athletes (41/485) (P < 0.0001). The total number of SCDs/year in athletes 15-35 years old, are approximately halved in 2000-10 compared to the years 1992-99. CONCLUSION: The increased risk of exercise-related SCD in HCM and ARVC underlines the importance of early detection and eligibility recommendations. There is a major reduction in deaths among athletes in the 2000s, compared to the previous decade. These results may partly be explained by improved acute preparedness for sudden cardiac arrest (CPR, defibrillation), but as a substantial percentage have preceding risk factors, such as symptoms and ECG-abnormalities, increased cardiac screening and increased general awareness, may also play a role.

Trends in prevalence of fatal surgical diseases at forensic autopsy.

BACKGROUND: In 1992, there were major changes in Swedish law of the deceased, which had led to a dramatic decrease in autopsy rates. The aim of this study was to investigate the prevalence of fatal or potential fatal surgical diseases within a Swedish forensic autopsy cohort, before and after this change in legislation. METHODS: Deaths referred for forensic autopsy at the Institution of Forensic Medicine, Lund University Hospital, Sweden, between 1970-1982 and 2000-2004, were studied regarding the prevalence of aorto-iliac diseases, acute abdomen and abdominal cancer. RESULTS: The forensic autopsy rates in the population during the two time periods were 14.0% (29 399 patients) and 5.3% (4487 patients), respectively. The total prevalence of surgical diseases has increased significantly from 67.3 (95% confidence interval 64.3-70.2) to 83.4 (74.9-91.8) per 1000 autopsies, respectively. The cause-specific mortality ratios in patients with fatal acute abdomen increased significantly from 16.5 (15.1-18.0) to 39.0 (33.2-44.8) per 1000 autopsies, respectively, and there was almost a three-time increase in patients with fatal gastrointestinal haemorrhage and acute alcohol-related pancreatitis. CONCLUSION: Forensic autopsy data continues to be invaluable, despite changes in legislation in Sweden, for epidemiological studies on fatal or potential fatal surgical diseases.

Toxicological findings and manner of death in autopsied users of anabolic androgenic steroids.

With the aim to characterize patterns in toxicological profile and manner of death in deceased users of anabolic androgenic steroids (AAS), a retrospective autopsy protocol study of 52 deceased users of AAS was undertaken. The AAS users were compared to 68 deceased users of amphetamine and/or heroin who were consecutively tested and found to be negative for AAS. Use of AAS was in the majority of cases (79%) associated with concomitant use of psychotropic substances. AAS-related deaths differed in several respects from deaths among users of heroin or amphetamine, most strikingly with regard to: (a) the median age at death, which was significantly lower for AAS users (24.5 years) than for users of heroin and/or amphetamine (34 and 40 years, respectively); (b) the manner of death, with AAS users dying significantly more often from homicide or suicide than users of other drugs; and (c) the body mass index (BMI), with AAS users exhibiting significantly higher BMI than users of other drugs. These results support the earlier reported association between use of AAS and use of other psychoactive substances. In addition, the data suggest that AAS users are more likely to become involved in incidents leading to violent death and have a higher risk of dying at a younger age than users of other drugs.

Causes of premature mortality in Swedish drug abusers: a prospective longitudinal study 1970-2006.

AIMS: To evaluate premature mortality and causes of death from young adulthood to middle age in a cohort of drug users followed during almost four decades. DESIGN: Follow-up study of a consecutive cohort of patients with drug abuse/dependence. METHODS: A cohort of 561 drug abusers, admitted to a detoxification and short-term rehabilitation unit 1970-1978 was followed to December 31st, 2006. Standardized interviews and hospital records with toxicological analyses were used for demographic data, substance use and psychiatric diagnoses at admission. For Follow-up analyses, autopsy protocols including toxicology tests and death certificates were obtained for assessment of causes of death which were coded according to ICD-10. Age-group standardized mortality ratios were calculated independently for both sexes. RESULTS: 204 persons (36.4%) were deceased by 2006. SMR was 5.94 for the cohort. Compared to an age- and gender-matched population, the risk of premature death was about eighteen times higher between the ages of 20-44 and about five times higher from 45 up to the age of 69. Of 120 (59%) drug-related deaths, 43 were opiate overdoses, and 3 were overdose from amphetamine. A total of 53 (26%) persons died violent deaths: 39 suicides, of which 25 were drug-related, 3 homicides and 12 accidents. The Swedish national causes of death register underestimated drug-related death by 37% and suicide by 85% compared to the results from this study. CONCLUSIONS: The cohort of drug abusers had an increased risk of premature often drug-related and violent death well into middle age, and to a great extent the drug addicts died from the same drug they had abused when they were first admitted for treatment. The underestimation of drug-related death and suicide in some national death cause registers could be reduced if the doctor routinely records ICD codes when issuing death certificates and autopsy protocols.

Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse.

Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been used as a marker of alcohol abuse in both urine and hair. This study investigated the value of EtG testing in post-mortem hair for diagnostic improvement of alcohol abuse in forensic medicine. Material from 70 consecutive medico-legal autopsies was collected in accordance with the recommendations on ethics by the Swedish National Board of Forensic Medicine. A method for determination of EtG in hair samples was developed using ultra performance liquid chromatography/electrospray tandem mass spectrometry (UPLC/ESI-MS/MS; LOQ, 2.5 pg/mg). The result of the EtG analysis was compared with the findings of phosphatidylethanol (PEth) in femoral whole blood, as measured by high performance liquid chromatography with an evaporative light-scattering detector (HPLC-ELSD; LOQ, 0.22 micromol/l). Evaluation of liver histology and anamnestic evidence of alcohol abuse of the deceased were taken in consideration for the interpretation. Measurable levels of EtG were present in 49 of the 70 autopsy cases whereas PEth was present in 36. Thirty-nine cases had EtG levels above the cutoff limit (> or = 30 pg/mg) compared with 29 for PEth (> or = 0.7 micromol/l). Fifteen cases had EtG as exclusive indicator for alcohol abuse compared with four cases for PEth. These findings suggest that measurements of EtG in hair may provide improved diagnostic information on alcohol abuse, due to a long retrospective time-window for detection and stability of EtG in hair in the decaying cadaver. However, an EtG level below the cutoff does not completely exclude previous alcohol abuse.