Undiagnosed disease in decedents with and without schizophrenia: an autopsy-based case-control study.

BACKGROUND: Individuals with schizophrenia (SCZ) suffer from higher morbidity and mortality than the general population. Some of this is due to concurrent somatic disease. AIMS: To identify and compare the somatic comorbidities antemortem (AM) and postmortem (PM) in autopsied decedents with SCZ and with no mental illness (NMI), using the Charlson Comorbidity Index (CCI). MATERIALS: A total of 106 autopsied decedents with SCZ and 156 decedents with NMI were included. AM diagnoses were sampled from Danish national health registers. PM diagnoses were included from forensic autopsies. Negative binomial regression models were used to test associations between age, sex, SCZ diagnosis, manner of death and the CCI score both AM and PM. RESULTS: The CCI score increased significantly from AM to PM for both decedents with SCZ and NMI (SCZ, AM 0.669 vs PM 1.208, p = 0.008) (NMI, AM 0.519 vs PM 1.218, p = 0.000). Regression analysis showed that age was significantly associated with the CCI score both AM and PM (AM, OR 1.044 [1.029-1.060] p ≤ 0.001) (PM, OR 1.028 [1.015-1.041], p ≤ 0.001). A diagnosis of SCZ was correlated with the CCI score AM but not PM (AM, OR 1.880 [1.207-2.928], p = 0.005) (PM, OR 1.170 [0.828-1.654], p = 0.374). CONCLUSION: The autopsies revealed undiagnosed diseases in both decedents with SCZ and NMI. The diseases were primarily of cardiovascular, pulmonary and gastrointestinal origin and may have contributed to premature mortality. Age was the only covariate significantly associated with the CCI score both AM and PM; the SCZ diagnosis was positively correlated to the CCI score before death.

Psychiatric disorders in a population of deceased drug users.

PURPOSE: To estimate the prevalence of psychiatric morbidity and dual diagnosis in a population of decedents with positive drug toxicology and evaluate changes over time between 2001-2002 and 2011-2012. MATERIALS AND METHODS: A total of 520 autopsied drug users with positive toxicology were included in the study from 2001 to 2002 and from 2011 to 2012. Materials included autopsy reports, toxicological screening during autopsy and data from the Danish national health registers, including psychiatric diagnoses from psychiatric hospitals and ambulatory functions, dispensed prescription use from pharmacies and registered treatment for drug use disorders. RESULTS: In 2001-2002, 63.3% of the decedents had only positive toxicology, 22.5% also had psychiatric morbidity, and 14.2% had a dual diagnosis. In 2011-2012, 56.4% had only positive toxicology, 26.1% also had psychiatric morbidity, and 17.5% had a dual diagnosis. None of the changes were significant. Decedents with only positive toxicology became older at time of death over time; decedents with psychiatric morbidity and a dual diagnosis did not. The prevalence of nonprescribed psychotropic medication, methadone and benzodiazepines increased. CONCLUSION: Decedents with psychiatric morbidity and dual diagnosis did not increase their lifespan over a 10-year period. Decedents with only positive toxicology increasingly consumed nonprescribed psychotropic medication and may have suffered from undiagnosed psychiatric disorders. The prevalence of prescribed and nonprescribed benzodiazepines and methadone increased and may have contributed to premature mortality.

Treatment Status and Use of Psychoactive Substances in Deceased Drug Users.

BACKGROUND: Studies on drug use are limited by the study populations available, which usually only include drug users in treatment settings. Therefore, the knowledge base is limited on drug users not entering treatment for drug use disorder (DUD). Using registers from departments of forensic medicine enables research on decedents with DUD, irrespective of treatment status. OBJECTIVES: The aim of this study is to characterize and compare drug users not receiving treatment and drug users receiving treatment, in relation to cause of death, toxicological findings, and use of nonprescribed medication. METHODS: Retrospective register-based study on deceased drug users with supplemental data from the Registry of Drug Abusers Undergoing Treatment and the Register of Medicinal Product Statistics in 2 observation periods: 2001-2002 and 2011-2012. RESULTS: Two-thirds of the population were not receiving treatment at the time of death in both observation periods. Drug users receiving treatment were more likely to die from accidental poisonings than drug users not receiving treatment. There was no difference in mean age at the time of death between the 2 groups, and both groups were older in the second observation period. There was no difference in toxicological findings according to treatment status and the 2 groups did not differ in the presence of nonprescribed medication found in the blood at the time of death. DISCUSSION/CONCLUSIONS: The proportion of drug users that received treatment prior to death has not increased, and deceased drug users are mostly not in treatment for their drug use at the time of death.

Post-mortem toxicology in young sudden cardiac death victims: a nationwide cohort study.

Aims: Several drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Methods and results: Deaths in persons aged 1-49 years were included over a 10-year period. Death certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected. Positive toxicology was defined as the presence of any substance (licit and/or illicit). All toxicological findings had previously been evaluated not to have caused the death (i.e. lethal concentrations were excluded). We identified 620 medico-legal autopsied cases of SCD, of which 77% (n = 477) were toxicologically investigated post-mortem, and 57% (n = 270) had a positive toxicology profile. Sudden cardiac death with positive toxicology had higher rates of sudden arrhythmic death syndrome (SADS), compared with SCD with negative toxicology (56% vs. 42%, P < 0.01). In total, 752 agents were detected, and polypharmacy (defined as the presence of more than one drug) was present in 61% (n = 164), all substances combined. Psychotropic drugs were the most frequent (62%, n = 467), and 82% (n = 385) were in pharmacological or subpharmacological levels. Conclusion: We found that more than half of all toxicologically investigated SCD victims have positive post-mortem toxicological findings, and polypharmacy is displayed in a considerable proportion. SCD with positive toxicology had higher rate of SADS, suggesting that the compounds may play a proarrhythmic role in these cases.

Factors associated with medico-legal autopsy of decedents with psychiatric disorders.

INTRODUCTION: Autopsy rates are declining worldwide, resulting in increasing selectivity in referral for forensic autopsy and increased uncertainty about the validity of assigned causes of death. Persons with psychiatric disorders have high rates of premature death but not all are referred for forensic autopsies. Knowledge is needed on which decedents with psychiatric disorders are chosen for forensic autopsy to determine whether causes of death are at risk of being misclassified among certain subgroups of decedents. METHODS: We conducted a nationwide register-based case-control study including all decedents with psychiatric disorders in Denmark in the period 1998-2015. Using multivariate logistic regression, we examined associations between demographic and socioeconomic factors, comorbidities, healthcare utilization, and referral for forensic autopsy, overall and stratified by age at death (<45, 45-64, ≥65 years). RESULTS: Of the 152,799 decedents in the study population, 7043 (4.61 %) had a forensic autopsy. Decedents referred for forensic autopsy were more likely to be young, have a history of substance use, and have schizophrenia or an affective disorder (factors listed in diminishing order of strength of association). Increasing severity of comorbidities as measured by the Charlson comorbidity index was associated with decreasing likelihood of being autopsied. Patterns of association with sex, alcohol use, habitation and education did not vary by age at death. Schizophrenia and drug use were most strongly associated with forensic autopsy in decedents < 45 years of age, whereas death early in the study period was more strongly associated with autopsy in the oldest age groups. DISCUSSION: The decision to refer a decedent for forensic autopsy was predominantly based on the decedent's age, history of drug use, and the absence of non-psychiatric comorbidities. Causes of death in decedents with comorbidities or recent contact with the healthcare system and decedents > 65 years may be more likely to be inaccurate, particularly in drug users.

The influence of comorbid disease on premature death due to natural and unnatural causes in persons with schizophrenia.

BACKGROUND: Comorbid disease may increase mortality in persons with schizophrenia, but how specific diseases are associated with natural and unnatural death in different age groups is unclear. AIMS: To investigate the association between eight major comorbid diseases and death from natural and unnatural causes in different age groups in persons with schizophrenia. METHOD: Retrospective register-based cohort study in 77,794 persons with schizophrenia in Denmark, 1977-2015. Using Cox regression in matched cohorts, we estimated hazard ratios for natural and unnatural death in three age groups (<55 years, 55-64 years, ≥65 years). RESULTS: Hypertensive disease, atrial fibrillation, coronary heart disease, cerebrovascular disease, heart failure, type 2 diabetes, liver disease and chronic kidney disease were all strongly associated with natural death, with the strongest associations observed in persons <55 years (hazard ratio [HR] range 1.98-7.19). The strongest associations were observed for heart failure (HR 7.19, 95 % confidence interval [CI] 5.57-9.28; HR 4.56, CI 3.85-5.40; HR 2.83, CI 2.53-3.17), liver disease (HR 4.66, CI 3.59-6.05; HR 4.70, CI 3.55-6.22; HR 2.57, CI 1.98-3.34) and chronic kidney disease (HR 6.59, CI 1.66-26.1; HR 7.37, CI 3.03-17.9; HR 2.86, CI 1.84-4.46) for persons <55 years, 55-64 years and ≥65 years, respectively. Liver disease was strongly associated with unnatural death in persons <55 years (HR 5.42, CI 3.01-9.75); associations with the remaining comorbidities were weaker. CONCLUSIONS: Comorbid disease was strongly associated with natural death, with the strength of the associations decreasing with age. Comorbid disease was also modestly associated with unnatural death, regardless of age.

Characterization of deceased drug users in Denmark based on treatment status: A nationwide retrospective autopsy study.

BACKGROUND: Many drug users are not receiving treatment for their drug use. Little is known about drug users not receiving treatment, as they are difficult to identify and recruit for research. METHODS: We identified 479 autopsied decedents with illegal/unmarketed drug or opioid agonist treatment positive toxicological screenings from 2015 to 2016 in Denmark. Toxicological screenings from autopsy, and information on treatment status at time of death, health care utilization, educational attainment, employment status and prescription drug use from Danish national health registers were used for comparison between groups. RESULTS: Drug users not in treatment constituted 63.3% of the study population and died at a younger age than those in treatment (41 vs. 44 years). Fatal overdose was the most common cause of death in both groups. Nearly thrice as many drug users not in treatment died from somatic causes compared with drug users in treatment (18.2% vs. 6.8%). On average, drug users not in treatment received fewer prescriptions prior to their deaths than those in treatment, but non-prescribed medications were equally prevalent among both groups (74.3% vs. 81.3%) except for non-prescribed methadone which was significantly less prevalent among drug users not in treatment (33.3% vs. 42.6%). CONCLUSION: Two-thirds of decedents were not in treatment at time of death. Drug users not in treatment died more often from somatic causes compared to those in treatment. Decedents had equal amounts of non-prescribed psychotropic medication in the blood, but non-prescribed methadone was more common among those in treatment at the time of death.

Psychiatric disorders are overlooked in patients with drug abuse.

INTRODUCTION: Psychiatric disease is overlooked in drug users. Patients with both drug abuse and a psychiatric disease - dual diagnosis - suffer decreased compliance to treatment and decreased life expectancy compared with single-diagnosis patients. Identifying the patients among either drug addicts or mentally ill patients is difficult. METHODS: All drug addicts autopsied at the Department of Forensic Medicine, University of Copenhagen, Denmark, in the years 1992, 2002 and 2012 were included. The group was divided into two subpopulations of possible dual diagnosis patients either according to police reports stating mental illness or to psychotropics found in the toxicology screening after autopsy. RESULTS: We found a rise in possible mental illness in both subpopulations in the study period. Drug addicts with psychotropics in the blood at the time of death increased from 3.1% in 1992 to 48.1% in 2012, and this group was significantly younger at the time of death than those without psychotropics in the blood. CONCLUSIONS: Suspected dual diagnosis patients have increased in number. They die earlier than their drug addict counterparts. Methadone remains the leading cause of death in all subpopulations. Possible causes are misuse of treatment and/or illegally bought methadone, wrongly assigned cause of death due to unknown tolerance and/or polydrug toxicity in combination with psychotropic medicine. FUNDING: none. TRIAL REGISTRATION: not relevant.