Evaluation of heroin-assisted treatment in Norway: protocol for a mixed methods study.

BACKGROUND: Opioid agonist treatment (OAT) for patients with opioid use disorder (OUD) has a convincing evidence base, although variable retention rates suggest that it may not be beneficial for all. One of the options to include more patients is the introduction of heroin-assisted treatment (HAT), which involves the prescribing of pharmaceutical heroin in a clinical supervised setting. Clinical trials suggest that HAT positively affects illicit drug use, criminal behavior, quality of life, and health. The results are less clear for longer-term outcomes such as mortality, level of function and social integration. This protocol describes a longitudinal evaluation of the introduction of HAT into the OAT services in Norway over a 5-year period. The main aim of the project is to study the individual, organizational and societal effects of implementing HAT in the specialized healthcare services for OUD. METHODS: The project adopts a multidisciplinary approach, where the primary cohort for analysis will consist of approximately 250 patients in Norway, observed during the period of 2022-2026. Cohorts for comparative analysis will include all HAT-patients in Denmark from 2010 to 2022 (N = 500) and all Norwegian patients in conventional OAT (N = 8300). Data comes from individual in-depth and semi-structured interviews, self-report questionnaires, clinical records, and national registries, collected at several time points throughout patients' courses of treatment. Qualitative analyses will use a flexible inductive thematic approach. Quantitative analyses will employ a wide array of methods including bi-variate parametric and non-parametric tests, and various forms of multivariate modeling. DISCUSSION: The project's primary strength lies in its comprehensive and longitudinal approach. It has the potential to reveal new insights on whether pharmaceutical heroin should be an integral part of integrated conventional OAT services to individually tailor treatments for patients with OUD. This could affect considerations about drug treatment even beyond HAT-specific topics, where an expanded understanding of why some do not succeed with conventional OAT will strengthen the knowledge base for drug treatment in general. Results will be disseminated to the scientific community, clinicians, and policy makers. TRIAL REGISTRATION: The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK), ref.nr.:195733.

Seroprevalence of SARS-CoV-2 and humoral immune responses to COVID-19 mRNA vaccines among people who use drugs - in the light of tailored mitigating strategies.

BACKGROUND: During the initial wave of the COVID-19 pandemic, there was a surprisingly low incidence of SARS-CoV-2 among People Who Use Drugs (PWUD) in Oslo, Norway, despite their heightened vulnerability regarding risk of infection and severe courses of the disease.This study aims to investigate the seroprevalence of SARS-CoV-2 antibodies among PWUD, their antibody responses to relevant virus infections and COVID-19 mRNA vaccines, and their vaccination coverage compared to the general population. METHODS: Conducted as a prospective cohort study, data was collected from residents in six institutions for homeless PWUD and users of a low-threshold clinic for opioid agonist treatment. Ninety-seven participants were recruited for SARS-CoV-2 seroprevalence analysis. Additional two participants with known positive SARS-CoV-2 test results were recruited for further analyses. Twenty-five participants completed follow-up. Data included questionnaires, nasal swabs and blood samples. Data on vaccination coverage was obtained from the National Vaccine Register. Serologic methods included detection of antibodies to relevant virus proteins, neutralizing antibodies to SARS-CoV-2, antibodies to the full-length spike protein, and receptor-binding domain from SARS-CoV-2. RESULTS: Among PWUD, antibodies to SARS-CoV-2 were detected in 2 out of 97 samples before vaccines against SARS-CoV-2 were available, comparable to a 2.8% frequency in population-based screening. Levels of serum antibodies to seasonal coronaviruses and Epstein-Barr-Virus (EBV) in PWUD were similar to population-based levels. After the second vaccine dose, binding and neutralizing antibody levels to SARS-CoV-2 in PWUD were comparable to controls. Eighty-four of PWUD received at least one dose of COVID-19 mRNA vaccine, compared to 89% in the general population. CONCLUSION: Results indicate that PWUD did not exhibit increased SARS-CoV-2 seroprevalence or elevated serum antibodies to seasonal coronaviruses and EBV. Moreover, vaccine responses in PWUD were comparable to controls, suggesting that vaccination is effective in conferring protection against SARS-CoV-2 also in this population.

Patients' satisfaction with heroin-assisted treatment: a qualitative study.

BACKGROUND: Heroin-assisted treatment (HAT) involves supervised dispensing of medical heroin (diacetylmorphine) for people with opioid use disorder. Clinical evidence has demonstrated the effectiveness of HAT, but little is known about the self-reported satisfaction among the patients who receive this treatment. This study presents the first empirical findings about the patients' experiences of, and satisfaction with, HAT in the Norwegian context. METHODS: Qualitative in-depth interviews with 26 patients in HAT were carried out one to two months after their enrollment. Analysis sought to identify the main benefits and challenges that the research participants experienced with this treatment. An inductive thematic analysis was conducted to identify the main areas of benefits and challenges. The benefits were weighed against the challenges in order to assess the participants' overall level of treatment satisfaction. RESULTS: Analysis identified three different areas of experienced benefits and three areas of challenges of being in this treatment. It outlines how the participants' everyday lives are impacted by being in the treatment and how this, respectively, results from the treatment's medical, relational, or configurational dimensions. We found an overall high level of treatment satisfaction among the participants. The identification of experienced challenges reveals factors that reduce satisfaction and thus may hinder treatment retention and positive treatment outcomes. CONCLUSIONS: The study demonstrates a novel approach to qualitatively investigate patients' treatment satisfaction across different treatment dimensions. The findings have implications for clinical practice by pointing out key factors that inhibit and facilitate patients' satisfaction with HAT. The identified importance of the socio-environmental factors and relational aspect of the treatment has further implications for the provision of opioid agonist treatment in general.

[Poor uptake of service provision at a drug-related emergency department ­ a qualitative study]. / Ubenyttet behandlingstilbud ved rusakuttmottak ­ en kvalitativ studie.

BACKGROUND: The patient pathway for follow-up after a drug overdose, which is an important part of Norway's national overdose strategy, started up on 1 January 2022. Four years earlier, a collaboration was initiated between the ambulance service and the drug-related emergency department at Oslo University Hospital with the same aim as this patient pathway: to provide emergency follow-up in the specialist health service after a drug overdose. Uptake of the follow-up provision was minimal, and the purpose of this study was to investigate the reasons behind this. MATERIAL AND METHOD: We used a case study design and carried out twelve qualitative interviews with representatives from the ambulance service, the drug-related emergency department and the service user group. A thematic analysis of the interviews was then conducted. RESULTS: The analysis revealed five thematic areas with different explanations for the poor uptake of the service provision. There was insufficient information about the provision, and the admission criteria were unclear. Communication issues between the ambulance service and the drug-related emergency department meant that the provision did not function as an emergency service. The service users' wishes after an overdose did not correspond fully with the provision, and uptake was sometimes associated with sanctions. INTERPRETATION: The results show that things could have been done differently at a local level, but also that the content of the patient pathway is unclear, and that general guidelines can lead to the provision being perceived as unsafe. The knowledge generated from this survey can help uncover areas that require improvement at a national level in the follow-up pathway after a drug overdose.

The effectiveness of integrated treatment in patients with substance use disorders co-occurring with anxiety and/or depression--a group randomized trial.

BACKGROUND: Integrated Treatment (IT) has proved effective in treating patients with Substance Use Disorders (SUD) co-occurring with severe Mental Disorders (MD), less is known about the effectiveness of IT for patients with SUD co-occurring with less severe MD.The aim of this study was to investigate the effectiveness of IT for patients with SUD co-occurring with anxiety and/or depression on the following parameters:1. The use of substances, as measured by the Alcohol Use Identification Test (AUDIT), the Drug Use Identification Test (DUDIT), and the Addiction Severity Index (EuropASI).2. The severity of psychiatric symptoms, as measured by the Symptom Check List 90 r (SCL 90R).3. The client's motivation for changing his/her substance use behaviour, as measured by the Substance Abuse Treatment Scale (SATSr). METHODS: This is a group randomized clinical trial comparing the effectiveness of IT to treatment as usual in Community Mental Health Centres (CMHCs). Five CMHCs were drawn to the Intervention Group (IG) and four CMHCs to the Control Group (CG). The allocation to treatment conditions was not blinded. New referrals were screened with the AUDIT and the DUDIT. Those who scored above the cut-off level of these instruments were assessed with the Structured Clinical Interview for DSM-IV 1 and 2. We included patients with anxiety and/or depression together with one or more SUDs. RESULTS: We included 55 patients in the IG and 21 in the CG. A linear multilevel model was used. Both groups reduced their alcohol and substance use during the trial, while there was no change in psychiatric symptoms in either group. However, the IG had a greater increase in motivation for substance use treatment after 12 months than had the CG with an estimate of 1.76, p = 0.043, CI95% (0.08; 3.44) (adjusted analyses). There were no adverse events. CONCLUSIONS: Integrated treatment is effective in increasing the motivation for treatment amongst patients with anxiety and/or depression together with SUD in outpatient clinics. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00447733.

Towards elimination of hepatitis C in Oslo: Cross-sectional prevalence studies among people who inject drugs.

BACKGROUND: Norway aims to eliminate hepatitis C virus (HCV) infection within the end of 2023. Before the introduction of direct-acting antivirals, the prevalence of chronic HCV infection among people who inject drugs (PWID) in Oslo was 40-45 %. The primary aim of the study was to assess changes in HCV prevalence among PWID in Oslo from 2018 to 2021. The secondary aim was to assess change in prevalence in selected subgroups. METHODS: Point prevalence studies were conducted in 2018 and 2021 among PWID attending low-threshold health services in downtown Oslo. Assessments included blood samples analysed for anti-HCV and HCV RNA, and a questionnaire about drug use. Information about previous HCV treatment was only collected in the 2021 cohort. We calculated HCV RNA prevalence estimates for 2018 and 2021 and used logistic regression analysis to identify factors associated with detectable HCV RNA and previous HCV treatment. RESULTS: A total of 281 and 261 participants were included in 2018 and 2021, respectively. The median age was 40.6 and 44.0 years, 73.7 % and 72.8 % were men, and 74.5 % and 78.6 % reported recent (past four weeks) injecting drug use, respectively. HCV RNA prevalence decreased significantly from 26.3 % (95 % CI 21.3-31.9) in 2018 (74 of 281) to 14.2 % (95 % CI 10.2-19.0) in 2021 (37 of 261). The odds of detectable HCV RNA were significantly lower in 2021 compared to 2018 (aOR 0.41; 95 % CI 0.26-0.67). In the 2021 cohort, detectable HCV RNA was associated with recent amphetamine injecting (aOR 7.21; 95 % CI 1.41-36.95), and mixed heroin/amphetamine injecting (aOR 7.97; 95 % CI 1.55-41.07). The odds of previous treatment were lower among women (aOR 0.52; 95 % CI 0.27-1.00). CONCLUSION: A substantial decrease in HCV RNA prevalence among PWID in Oslo between 2018 and 2021 was observed. To reach elimination, adaptive services must be further developed.

Hepatitis C treatment uptake among people who inject drugs in Oslo, Norway: A registry-based study.

BACKGROUND: Improving HCV treatment uptake among people who inject drugs (PWID) is crucial to achieving the WHO elimination targets. The aims were to evaluate HCV treatment uptake and HCV RNA prevalence in a large cohort of PWID in Norway. METHODS: Registry-based observational study where all users of the City of Oslo's low-threshold social and health services for PWID between 2010-2016 (n = 5330) were linked to HCV notifications (1990-2019) and dispensions of HCV treatment, opioid agonist treatment (OAT) and benzodiazepines (2004-2019). Cases were weighted to account for spontaneous HCV clearance. Treatment rates were calculated using person-time of observation, and factors associated with treatment uptake were analysed using logistic regression. HCV RNA prevalence was estimated among individuals alive by the end of 2019. RESULTS: Among 2436 participants with chronic HCV infection (mean age 46.8 years, 30.7% female, 73.3% OAT), 1118 (45.9%) had received HCV treatment between 2010-2019 (88.7% DAA-based). Treatment rates increased from 1.4/100 PY (95% CI 1.1-1.8) in the pre-DAA period (2010-2013) to 3.5/100 PY (95% CI 3.0-4.0) in the early DAA period (2014-2016; fibrosis restrictions) and 18.4/100 PY (95% CI 17.2-19.7) in the late DAA period (2017-2019; no restrictions). Treatment rates for 2018 and 2019 exceeded a previously modelled elimination threshold of 50/1000 PWID. Treatment uptake was less likely among women (aOR 0.74; 95% CI 0.62-0.89) and those aged 40-49 years (aOR 0.74; 95% CI 0.56-0.97), and more likely among participants with current OAT (aOR 1.21; 95% CI 1.01-1.45). The estimated HCV RNA prevalence by the end of 2019 was 23.6% (95% CI 22.3-24.9). CONCLUSION: Although HCV treatment uptake among PWID increased, strategies to improve treatment among women and individuals not engaged in OAT should be addressed.

People who use drugs show no increase in pre-existing T-cell cross-reactivity toward SARS-CoV-2 but develop a normal polyfunctional T-cell response after standard mRNA vaccination.

People who use drugs (PWUD) are at a high risk of contracting and developing severe coronavirus disease 2019 (COVID-19) and other infectious diseases due to their lifestyle, comorbidities, and the detrimental effects of opioids on cellular immunity. However, there is limited research on vaccine responses in PWUD, particularly regarding the role that T cells play in the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we show that before vaccination, PWUD did not exhibit an increased frequency of preexisting cross-reactive T cells to SARS-CoV-2 and that, despite the inhibitory effects that opioids have on T-cell immunity, standard vaccination can elicit robust polyfunctional CD4+ and CD8+ T-cell responses that were similar to those found in controls. Our findings indicate that vaccination stimulates an effective immune response in PWUD and highlight targeted vaccination as an essential public health instrument for the control of COVID-19 and other infectious diseases in this group of high-risk patients.

A cross-sectional study of patients with and without substance use disorders in Community Mental Health Centres.

BACKGROUND: Epidemiological studies have consistently established high comorbidity between psychiatric disorders and substance use disorders (SUD). This comorbidity is even more prominent when psychiatric populations are studied. Previous studies have focused on inpatient populations dominated by psychotic disorders, whereas this paper presents findings on patients in Community Mental Health Centres (CMHCs) where affective and anxiety disorders are most prominent. The purpose of this study is to compare patients in CMHCs with and without SUD in regard to differences in socio-demographic characteristics, level of morbidity, prevalence of different diagnostic categories, health services provided and the level of improvement in psychiatric symptoms. METHODS: As part of the evaluation of the National Plan for Mental Health, all patients seen in eight CMHCs during a 4-week period in 2007 were studied (n = 2154). The CMHCs were located in rural and urban areas of Norway. The patients were diagnosed according to the ICD-10 diagnoses and assessed with the Health of the Nation Outcome Scales, the Alcohol Use Scale and the Drug Use Scale. RESULTS: Patients with SUD in CMHCs are more frequently male, single and living alone, have more severe morbidity, less anxiety and mood disorders, less outpatient treatment and less improvement in regard to recovery from psychological symptoms compared to patients with no SUD. CONCLUSION: CMHCs need to implement systematic screening and diagnostic procedures in order to detect the special needs of these patients and improve their treatment.

Identifying co-occurring substance use disorders in community mental health centres. Tailored approaches are needed.

BACKGROUND: Increasing evidence shows that substance use disorders (SUD) and psychiatric illness co-occur, and that this co-morbidity renders treatment more difficult and results in greater use of health services. Thus, clinical routines to identify SUD amongst patients in mental healthcare should have high priority in order to provide optimal treatment. AIM: In this study, we examine whether common and well-known substance use measures are appropriate in detecting SUD in Community Mental Health Centres (CMHCs). MATERIAL AND METHODS: The present study used a subset of data from an evaluation of the National Plan for Mental Health. Clinicians at eight CMHCs registered socio-demographic and treatment information about their patients during a 4-week period in 2007. This included diagnostic measures, the Alcohol and Drug Use Scales and the substance use item of the Health of the Nation Outcome Scales. Prevalence rates from the different substance use measures and the observed agreement between them were calculated. The prevalence rates were compared with other estimates of substance use prevalence. RESULTS: All the different measures gave low prevalence rates of SUD, and the inter-measure agreement was poor. A combination of the measures gave prevalence rates closer to what is expected from previous epidemiological studies. CONCLUSION: The CMHCs participating in this study lack sufficient diagnostic routines and specific instruments to identify SUD. Clinical research that relies on methods used in this study will need combined approaches to provide reliable findings. Both clinical practice and research would benefit from valid, reliable screening methods and diagnostic procedures.

Hepatitis C treatment and reinfection surveillance among people who inject drugs in a low-threshold program in Oslo, Norway.

BACKGROUND: The aims were to evaluate HCV treatment effectiveness, estimate reinfection rates, and demonstrate the feasibility of reinfection surveillance and retreatment among marginalized people who inject drugs (PWID). METHODS: Prospective observational study including consecutive HCV RNA positive individuals attending a low-threshold clinic in Oslo, Norway, between 2013 and 2020. Participants were offered individually tailored HCV treatment and post-treatment HCV RNA surveillance at three months intervals. RESULTS: Of 488 HCV RNA positive individuals, 363 initiated treatment (median age 48.7 years, 72.5% male, 17.2% liver cirrhosis, 54.3% unstable housing). All participants had a history of injecting drug use, 71.1% received opioid agonist treatment, and 70.1% reported recent (past 3 months) injecting. In intention-to-treat analysis, excluding those with HCV RNA results pending, virologic response was achieved in 306 of 340 (90.0%) participants. In modified intention-to-treat analysis, also excluding those with loss to follow-up during treatment, virologic response was achieved in 306 of 323 (94.7%). Virologic response was not associated with recent injecting drug use or socio-demographic factors. Reinfection surveillance was accomplished in 297 individuals (308.2 PY of follow-up; median 0.50 years). Eight cases of reinfection were detected for an incidence of 2.60/100 PY (95% CI 1.12-5.11) overall, and 3.74/100 PY (95% CI 1.62-7.37) among those with injecting drug use during follow-up (n = 205). Reinfection was associated with younger age (IRR 0.37; 95% CI 0.18-0.74), and all cases occurred in participants aged below 49 years with ongoing injecting drug use who reported mixed heroin/amphetamine injecting. Successful retreatment was provided in all cases and no second reinfections were observed. CONCLUSION: The findings consolidate previous evidence supporting the effectiveness of HCV treatment among PWID, provide novel data on reinfection rates and associated factors, and demonstrate the feasibility of reinfection surveillance and retreatment in a real-world setting.

When research meets reality-lessons learned from a pragmatic multisite group-randomized clinical trial on psychosocial interventions in the psychiatric and addiction field.

UNLABELLED: Research on treatments for patients with co-occurring psychiatric and substance use disorders is of core importance and at the same time highly challenging as it includes patients that are normally excluded from clinical studies. Such research may require methodological adaptations which in turn create new challenges. However, the challenges that arise in such studies are insufficiently discussed in the literature. The aim of this methodology paper is, firstly, to discuss the methodological adaptations that may be required in such research; secondly, to describe how such adaptations created new challenges in a group-randomized clinical trial on Integrated Treatment amongst patients with co-occurring psychiatric and substance use disorders. We also discuss how these challenges might be understood and highlight lessons for future research in this field. TRIAL REGISTRATION: NCT00447733.