Who receives heroin-assisted treatment? A comparison of patients receiving opioid maintenance treatment in Denmark.

BACKGROUND: Since 2010, heroin-assisted treatment (HAT) has been one of the treatment options available to people with opioid use disorder (OUD) in Denmark. This study aimed to characterize HAT patients at treatment start and compare their individual characteristics to those of patients entering traditional opioid maintenance treatment (OMT) with methadone or buprenorphine during the same period. METHODS: Patients who initiated HAT or OMT with methadone or buprenorphine in Denmark from 2010 to 2018 were included (n=6798). Multiple national registers were linked to compare treatment groups in terms of socio-demographic variables, previous OUD treatment episodes, hospital-based care, and criminal conviction history. RESULTS: Nearly all HAT patients had a history of methadone treatment (91%) and half had residential treatment experience (48%). In the year previous to admission, HAT patients recorded the highest percentages of non-fatal overdoses (12%) and chronic hepatitis C diagnoses (16%), and the lowest percentages of psychiatric disorders (11%) compared to traditional OMT patients. Criminal convictions were also common: 39% of the HAT group had committed a property crime and 18% a drug-related crime the year before HAT entry. During the study period, an overall reduction in OMT enrollments for each year was recorded. The HAT proportion to the total remained fairly stable (4%-10%), while the buprenorphine proportion increased. CONCLUSIONS: In Denmark, OMT patients exhibited numerous vulnerabilities at treatment start, and among the patient groups, HAT patients were the most burdened. HAT seems to reach the target group and adhere to formulated eligibility criteria.

Large variations in all-cause and overdose mortality among >13,000 patients in and out of opioid maintenance treatment in different settings: a comparative registry linkage study.

Background: Opioid maintenance treatment (OMT) has the potential to reduce mortality rates substantially. We aimed to compare all-cause and overdose mortality among OMT patients while in or out of OMT in two different countries with different approaches to OMT. Methods: Two nation-wide, registry-based cohorts were linked by using similar analytical strategies. These included 3,637 male and 1,580 female patients enrolled in OMT in Czechia (years 2000-2019), and 6,387 male and 2,078 female patients enrolled in OMT in Denmark (years 2007-2018). The direct standardization method using the European (EU-27 plus EFTA 2011-2030) Standard was employed to calculate age-standardized rate to weight for age. All-cause and overdose crude mortality rates (CMR) as number of deaths per 1,000 person years (PY) in and out of OMT were calculated for all patients. CMRs were stratified by sex and OMT medication modality (methadone, buprenorphine, and buprenorphine with naloxone). Results: Age-standardized rate for OMT patients in Czechia and Denmark was 9.7/1,000 PY and 29.8/1,000 PY, respectively. In Czechia, the all-cause CMR was 4.3/1,000 PY in treatment and 10.8/1,000 PY out of treatment. The overdose CMR was 0.5/1,000 PY in treatment and 1.2/1,000 PY out of treatment. In Denmark, the all-cause CMR was 26.6/1,000 PY in treatment and 28.2/1,000 PY out of treatment and the overdose CMR was 7.3/1,000 PY in treatment and 7.0/1,000 PY out of treatment. Conclusion: Country-specific differences in mortality while in and out of OMT in Czechia and Denmark may be partly explained by different patient characteristics and treatment systems in the two countries. The findings contribute to the public health debate about OMT management and may be of interest to practitioners, policy and decision makers when balancing the safety and accessibility of OMT.

Cause-Specific Mortality among Patients in Treatment for Opioid Use Disorder in Multiple Settings: A Prospective Comparative Cohort Study.

INTRODUCTION: Among people receiving current or previous opioid maintenance treatment (OMT), the leading cause of premature death is an opioid overdose. However, other causes of mortality remain high in this group. An understanding of causes of deaths across multiple settings can be useful in informing more comprehensive prevention responses. The aim of this study was to describe all non-overdose causes of death in three national cohorts (Czechia, Denmark, and Norway) among OMT patients and to explore associations of non-overdose mortality with age and gender. METHODS: This prospective comparative cohort study used national mortality registry databases for OMT patients from Czechia (2000-2019), Denmark (2000-2018), and Norway (2010-2019). Crude mortality rates and age-standardized mortality rates (ASMRs) were calculated as deaths per 1,000 person years for cause-specific mortality. RESULTS: In total, 29,486 patients were included, with 5,322 deaths recorded (18%). We found variations in causes of death among the cohorts and within gender and age groups. The leading non-overdose causes of death were accidents in Czechia and Denmark, and neoplasms in Norway. Cardiovascular deaths were highest in Czechia, particularly for women in OMT (ASMR 3.59 vs. 1.24 in Norway and 1.87 in Denmark). CONCLUSION: This study found high rates of preventable death among both genders and all age groups. Different demographic structures, variations in risk exposure, as well as variations in coding practices can explain the differences. The findings support increased efforts towards screening and preventative health initiatives among OMT patients specific to the demographic characteristics in different settings.

PriSUD-Nordic-Diagnosing and Treating Substance Use Disorders in the Prison Population: Protocol for a Mixed Methods Study.

BACKGROUND: A large proportion of the prison population experiences substance use disorders (SUDs), which are associated with poor physical and mental health, social marginalization, and economic disadvantage. Despite the global situation characterized by the incarceration of large numbers of people with SUD and the health problems associated with SUD, people in prison are underrepresented in public health research. OBJECTIVE: The overall objective of the PriSUD (Diagnosing and Treating Substance Use Disorders in Prison)-Nordic project is to develop new knowledge that will contribute to better mental and physical health, improved quality of life, and better life expectancies among people with SUD in prison. METHODS: PriSUD-Nordic is based on a multidisciplinary mixed method approach, including the methodological perspectives of both quantitative and qualitative methods. The qualitative part includes ethnographic fieldwork and semistructured interviews. The quantitative part is a registry-based cohort study including national registry data from Norway, Denmark, and Sweden. The national prison cohorts will comprise approximately 500,000 individuals and include all people imprisoned in Norway, Sweden, and Demark during the period from 2000 to 2019. The project will investigate the prison population during three different time periods: before imprisonment, during imprisonment, and after release. RESULTS: PriSUD-Nordic was funded by The Research Council of Norway in December 2019, and funding started in 2020. Data collection is ongoing and will be completed in the first quarter of 2022. Data will be analyzed in spring 2022 and the results will be disseminated in 2022-2023. The PriSUD-Nordic project has formal ethical approval related to all work packages. CONCLUSIONS: PriSUD-Nordic will be the first research project to investigate the epidemiology and the lived experiences of people with SUD in the Nordic prison population. Successful research in this field will have the potential to identify significant areas of benefit and will have important implications for ongoing policy related to interventions for SUD in the prison population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35182.

A retrospective cohort study of medication dispensing at pharmacies: Administration matters!

BACKGROUND: Opioid agonist treatment (OAT) for opioid use disorders may be delivered at treatment clinics or dispensed from pharmacies, however the type of delivery may be associated with different risks and benefits. The aim of the study was to investigate whether dispensing of methadone or buprenorphine at pharmacies during treatment for opioid use disorders was associated with adverse outcomes. METHODS: Retrospective cohort study using a national, linked, population-level data set from Denmark. Patients included were between 18 and 75 years, living in Denmark, and admitted for treatment for opioid use disorders during 2000-2016 (n = 9299). Cox proportional hazards regression was estimated for convictions, non-fatal overdoses, and death, after the first dispensing of either methadone or buprenorphine from a pharmacy after starting treatment. FINDINGS: Of all patients, 68 % had methadone and 31 % had buprenorphine dispensed at a pharmacy. Compared with the time prior to pharmacy dispension, the risk of criminal convictions increased after having methadone dispensed from a pharmacy (adjusted hazard ratio (aHR) = 1.22, 95 % confidence interval (CI) = 1.16-1.28), non-fatal overdoses (aHR = 1.55, CI 1.41-1.71), and all-cause mortality (aHR = 1.54, CI = 1.43-1.76). After having buprenorphine dispensed at a pharmacy, risk of criminal convictions increased (aHR = 1.08, CI = 1.01-1.16) and non-fatal overdoses (aHR = 1.31, CI = 1.18-1.45), but not all-cause mortality (aHR = 1.07, CI = 0.94-1.23). CONCLUSIONS: For almost all outcomes investigated across medication type, the risk of adverse events increased following a switch from clinic dispension to pharmacy dispension of medications in OAT. Medically responsible and safe provision of OAT may often require more clinical follow-up than what is typically provided when medication is dispensed at pharmacies.

Opioid maintenance treatment in the Czech Republic, Norway and Denmark: a study protocol of a comparative registry linkage study.

INTRODUCTION: Opioid maintenance treatment (OMT) varies across settings and between countries. We plan to use data from several nationwide health and population registers to further improve the knowledge base established from earlier studies. Our aim is to study OMT adherence trajectories and to identify factors associated with improved outcomes for OMT patients across the Czech Republic, Norway and Denmark, in order to further improve OMT and our understanding of the key elements of treatment success. METHODS AND ANALYSIS: The registry-based cohort approach across the three countries allows us to link data from a range of registers on the individual level, by using personal identifiers in nationwide cohorts of OMT and non-OMT patients and the general non-using populations. A total of ~21 500 OMT patients over the last two decades in all three countries will be included in the study. The following outcome variables (based on the International Classification of Diseases, 10th Revision codes) will be obtained from relevant registers: treatment adherence to OMT, comorbidity (somatic and mental health), and all-cause and cause-specific mortality. Outcomes of the country-specific analyses will be pooled. ETHICS AND DISSEMINATION: The national OMT cohorts have been approved by the ethics committees in the respective countries. Data will be stored according to national and local guidelines and treated confidentially, and all data will be analysed separately for each country and compared across countries. Findings will be disseminated in peer-reviewed scientific journals, national and international conferences, and in briefings to inform clinical decision-making.

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.

Opioid maintenance treatment of pregnant women in the Scandinavian countries.

Background: WHO guidelines emphasise the need for descriptions of clinical practice and observational studies on risk and benefits of pharmacotherapies in pregnancy. The aims of the present study were to: (1) Describe opioid maintenance treatment (OMT) in the Scandinavian countries in general, and specifically for pregnant women, (2) Describe a project which utilises a new approach using registry-linkage data to examine associations between prenatal exposure to OMT and child outcomes: a Scandinavian cohort study of pregnant women in OMT during pregnancy (ScopeOMT). Data: Guidelines describing the treatment of persons with opioid use disorders in general, and specifically for pregnant women. Scandinavian registry-linkage data from ScopeOMT. Results: Registry data show that approximately 800 pregnant women received OMT during pregnancy in the period of the ScopeOMT study. Similarities across the Scandinavian countries include access to free healthcare and treatment; multidisciplinary teams trained to support pregnant women in OMT; buprenorphine as the recommended drug when initiating therapy; and a holistic focus on the patients' lives. An important difference is that Norwegian women who use illegal substances that may harm the foetus may be admitted - voluntarily, or against their will - for parts of, or the remainder of the pregnancy to inpatient treatment at specialised clinics. Conclusion: Many similarities in the treatment provided to opioid-dependent persons in the Scandinavian countries place this area in an excellent position to combine the efforts and carry out observational studies concerning the safety of OMT during pregnancy.

Incidence and predictors of drug overdoses among a cohort of >10,000 patients treated for substance use disorder.

BACKGROUND: Drug overdoses remain a significant public health burden throughout the world. This study assessed the incidence and predictors of non-fatal and fatal drug overdoses among patients with an opioid use, treated for drug use disorders (DUD) at public treatment centers in Denmark. METHODS: A consecutive cohort of patients (n = 11,199) were tracked from date of first registered enrollment between the year 2000 and 2010 to first registered drug overdose, death or December 31st 2010, whichever occurred first. Competing-risks regression models were fitted to estimate the sub hazard ratios (SHRs) of non-fatal and fatal drug overdoses and confounding risk factors. RESULTS: A total of 3186 (28%) patients experienced a non-fatal drug overdose during follow-up, and 572 (6%) died from an overdose. Use of benzodiazepines (SHR: 1.15 95% CI 1.03, 1.28) was significantly associated with non-fatal overdose. Intravenous drug use and previous hospitalization for a non-fatal overdose increased the risk of later non-fatal (SHR: 1.57 95% CI 1.42, 1.73) and fatal overdoses (SHR: 1.43 95% CI 1.12, 1.82). CONCLUSIONS: Patients who use opioids remain at risk of overdoses for a long time after discharge from drug treatment. Besides relevant monitoring and psychosocial support in opioid maintenance treatment, there is a need for informing and educating opioid users in risk factors and preventive measures in settings where they are often difficult to access for traditional treatment services.

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.

Methadone-Related Overdose Deaths in a Liberal Opioid Maintenance Treatment Programme.

BACKGROUND/AIMS: Increasing rates of overdose deaths involving opioid maintenance treatment (OMT) medications and particularly methadone have been observed concurrently with the implementation of liberal OMT strategies (i.e. minimum of control and high doses prescribed). This study examined methadone-related overdose deaths in a liberal OMT programme. METHODS: Drug-overdose deaths (n = 130) with detection of methadone in Copenhagen, Aarhus, and Odense Municipality, Denmark, during the period 2008-2011 were identified from a registry. Cases with and without prescribed methadone as OMT were compared. Treatment delivery strategy among OMT-prescribed methadone cases was investigated. RESULTS: Methadone was detected in 130 overdose deaths (71.4% of all overdose deaths). Among these, 63.1% were receiving methadone maintenance treatment. Of these, 79.3% had co-detection of benzodiazepines. Concomitant detection of heroin, non-prescribed benzodiazepines, and younger age were associated with having non-prescribed methadone in the toxicological findings (adjusted OR 3.1, 4.0 and 9.5, respectively). Of the decedents, 43.8% were prescribed a higher methadone dose than recommended (>120 mg daily), of which 80.0% did not have supervised intake of methadone. CONCLUSIONS: Liberal OMT access does not necessarily prevent overdose deaths overall. Prescription of higher doses of methadone combined with benzodiazepines may result in an increased risk of overdose for individuals in as well as outside OMT.

Benzodiazepine prescription for patients in treatment for drug use disorders: a nationwide cohort study in Denmark, 2000-2010.

BACKGROUND: Benzodiazepines are frequently prescribed to patients with drug use disorders. However, it has previously been difficult to distinguish whether this frequent prescribing was due to underlying psychiatric disorders or inappropriate prescribing. In a nationwide cohort study, we investigated the prescribing of benzodiazepines to patients with drug use disorders in connection with treatment admission. METHODS: Benzodiazepine prescriptions to patients (N = 33203) aged 18 to 67 years admitting for outpatient treatment for drug use disorders in Denmark, 2000 to 2010, were studied by using linked data from nationwide health registries. Factors associated with increasing amounts of benzodiazepine use within the first year after admission were assessed by multinomial logistic regression. Proportions of very long-term benzodiazepine prescription were calculated. RESULTS: During the first year after admission to treatment, 26.2 % of patients were prescribed benzodiazepines. Of these, 35.5 % were prescribed benzodiazepines at dose levels that might indicate inappropriate use (>365 Defined Daily Dose per year), and 34.6 % were prescribed more than one type of benzodiazepines. Diazepam was the most commonly prescribed type. Among patients with opioid use, 43.2 % were prescribed benzodiazepines which were three times higher than for patients with cannabis (12.2 %) or central stimulating drugs (13.8 %) as their primary drug use. Admitting to treatment for a drug use disorder did not increase the specialized psychiatric treatment coverage of this patient group, disregarding use of prescribed benzodiazepines. 29.5 % were new users of prescribed benzodiazepines, and of these, 27.5 % continued into very long-term use (≥4 years after admission) during the study period. CONCLUSIONS: Benzodiazepines were commonly prescribed to patients admitting to treatment for drug use disorders, and included prescription of multiple and non-optimal types, high doses, and very long-term prescriptions. These findings point towards inappropriate prescribing of benzodiazepines in many cases more than treatment for psychiatric disorders.