Federal opioid agonist therapy policy: interrupted time series analysis of the impact of the methadone exemption removal across eight provinces in Canada.

BACKGROUND: Federal deregulation of opioid agonist therapies are an attractive policy option to improve access to opioid use disorder care and achieve widespread beneficial impacts on growing opioid-related harms. There have been few evaluations of such policy interventions and understanding effects can help policy planning across jurisdictions. METHODS: Using health administrative data from eight of ten Canadian provinces, this study evaluated the impacts of Health Canada's decision in May 2018 to rescind the requirement for Canadian health professionals to obtain an exemption from the Canadian Drugs and Substance Act to prescribe methadone for opioid use disorder. Over the study period of June 2017 to May 2019, we used descriptive statistics to capture overall trends in the number of agonist therapy prescribers across provinces and we used interrupted time series analysis to determine the effect of this decision on the trajectories of the agonist therapy prescribing workforces. RESULTS: There were important baseline differences in the numbers of agonist therapy prescribers. The province with the highest concentration of prescribers had 7.5 more prescribers per 100,000 residents compared to the province with the lowest. All provinces showed encouraging growth in the number of prescribers through the study period, though the fastest growing province grew 4.5 times more than the slowest. Interrupted time series analyses demonstrated a range of effects of the federal policy intervention on the provinces, from clearly positive changes to possibly negative effects. CONCLUSIONS: Federal drug regulation policy change interacted in complex ways with provincial health professional regulation and healthcare delivery, kaleidoscoping the effects of federal policy intervention. For Canada and other health systems such as the US, federal policy must account for significant subnational variation in OUD epidemiology and drug regulation to maximize intended beneficial effects and mitigate the risks of negative effects.

"Naloxone? Not for me!" First cross-assessment by patients and healthcare professionals of the risk of opioid overdose.

BACKGROUND: Opioid-related mortality is a rising public health concern in France, where opioids were in 2021 implicated in 75% of overdose deaths. Opioid substitution treatment (OST) was implicated in almost half of deaths related to substance and drug abuse. Although naloxone could prevent 80% of these deaths, there are a number of barriers to the distribution of take-home naloxone (THN) among opioid users in France. This study is the first one which compares patients' self-assessment of the risk of future opioid overdose with the hetero-assessment provided by healthcare professionals in a population of individuals eligible for naloxone. METHODS: This was a multicenter descriptive observational study carried out in pharmacies across the Pays de la Loire region (France) during April and May 2022. All adult patients who visited a participating pharmacy for a prescription of OST and provided oral informed consent were enrolled in the study. Retrospective data were collected through cross-sectional interviews conducted by the pharmacist with the patient, utilizing an ad hoc questionnaire. The patient's self-assessment of overdose risk was evaluated using a Likert scale from 0 to 10. The pharmacist relied on the presence or absence of overdose risk situations defined by the French Health Authority (HAS). The need to hold THN was assessed using a composite criterion. RESULTS: A total of 34 patients were interviewed; near one third were aware of the existence of THN and a minority had THN in their possession. Out of the 34 participants, 29 assessed their own risk of future opioid overdose: 65.5% reported having zero risk, while 6.9% believed they had a high risk. Nevertheless, at least one risk situation of opioid overdose was identified according to HAS criteria in 73.5% of the participants (n = 25). Consequently, 55% of the participants underestimated their risk of experiencing a future opioid overdose. Yet, dispensing THN has been judged necessary for 88.2% of the participants. CONCLUSION: This study underscored the imperative need to inform not only healthcare professionals but also the patients and users themselves on the availability of THN and the risk situations of opioid overdose.

Attention-deficit/hyperactivity disorder (ADHD) symptoms and their relation to diagnosed ADHD, sociodemographic characteristics, and substance use among patients receiving opioid agonist therapy: a Norwegian cohort study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms may challenge sufficient treatment of substance use and mental disorders. The literature on the extent of such symptoms among patients receiving opioid agonist therapy (OAT) is scarce. This study examined ADHD symptoms using the ADHD self-report scale (ASRS) and the association between the 'ASRS-memory' and 'ASRS-attention' scores and substance use and sociodemographic characteristics among patients receiving OAT. METHODS: We used data from assessment visits of a cohort of patients in Norway. In total, 701 patients were included from May 2017 to March 2022. All patients responded at least once to two ASRS questions assessing memory and attention, respectively. Ordinal regression analyses were performed to investigate whether the two obtained scores were associated with age, sex, frequent substance use, injecting use, housing status, and educational attainment at baseline, i.e., the first assessment, and over time. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Additionally, a subsample of 225 patients completed an extended interview, including the ASRS-screener and collection of registered mental disorder diagnoses from the medical records. Standard cutoffs were used to define the presence of each ASRS symptom or a positive ASRS-screener ('ASRS-positive'). RESULTS: At baseline, 428 (61%) and 307 (53%) patients scored over the cutoffs on the 'ASRS-memory' and 'ASRS-attention,' respectively. Frequent cannabis use was associated with higher 'ASRS-memory' (OR: 1.7, 95% CI: 1.1-2.6) and 'ASRS-attention' (1.7, 1.1-2.5) scores compared with less or no use at baseline, though reduced score on the 'ASRS-memory' over time (0.7, 0.6-1.0). At baseline, frequent stimulant use (1.8, 1.0-3.2) and low educational attainment (0.1, 0.0-0.8) were associated with higher 'ASRS-memory' scores. In the subsample fulfilling the ASRS-screener, 45% of the patients were 'ASRS-positive,' of whom 13% with a registered ADHD diagnosis. CONCLUSIONS: Our findings illustrate a relationship between the ASRS-memory and -attention scores and frequent cannabis and stimulant use. Furthermore, nearly half of the subsample was 'ASRS-positive.' Patients receiving OAT might benefit from being further assessed for ADHD, but improved diagnostic methods are required.

Participation in screening for breast and cervical cancer among women with current or previous drug use: a survey study.

BACKGROUND: Women with current or previous drug use (WCPDU) have an increased risk of poor breast and cervical cancer outcomes. Screening is known to decrease the mortality of these common cancer forms, but screening participation has been sparsely investigated among women with drug dependency. The aim of this study was to assess participation in screening for breast and cervical cancer among WCPDU. METHODS: We recruited WCPDU to a survey study, from six opioid substitution treatment (OST) clinics and one needle exchange program (NEP) in Malmö, Sweden, and through the Drug Users Union in Stockholm, Sweden. The survey was constructed according to results from focus group discussions about cancer screening in a sample of women in OST. Survey data were analyzed using descriptive statistics. We analyzed associations between non-compliance to screening and healthcare contact (OST, NEP or none) by logistic regression analysis; unadjusted and adjusted for age, native language, housing situation, educational attainment and main source of income. RESULTS: A total of 298 women (median age 43 years) responded to the survey. The self-reported compliance with cancer screening recommendations was 29% for breast cancer screening and 41% for cervical cancer screening. Non-compliance with cervical cancer screening was associated with NEP participation in univariate but not multivariate analysis. We did not find an association between non-compliance with breast cancer screening and healthcare contact. Non-compliance with screening for cervical cancer was also associated with unstable housing in univariate and multivariate analyses, and inversely associated with increasing age in a univariate analysis. Non-compliance with breast cancer was associated with unstable housing in a univariate analysis, and inversely associated with not having Swedish as a native language in a multivariate analysis. CONCLUSION: The self-reported compliance with the national cancer screening programs for breast cancer and cervical cancer of WCPDU is notably lower than in the Swedish general population. Women with unstable housing seem to be particularly vulnerable to non-compliance with cancer screening. Interventions to minimize barriers to cancer screening are crucial to decrease the increased cancer morbidity and mortality among WCPDU.

Feasibility and Short-Term Effects of Low-Threshold Opioid Substitution Treatment during the COVID-19 Pandemic in Hamburg, Germany.

INTRODUCTION: After rapidly opening up a low-threshold clinic to support heavily opioid-dependent persons at the beginning of the COVID-19 pandemic in April 2020 in Hamburg (Germany), this non-interventional study evaluated the feasibility and short-term effects of opioid substitution treatment (OST). The low-threshold concept was customized for the pandemic situation and is the first of its kind in Germany. METHODS: Patients who had already begun treatment were questioned in two assessments, at T1 shortly after beginning treatment and at T2 6 months later. The primary outcome criterion was their quality of life using the OSTQOL. Secondary criteria included retention rate, their mental and physical health (measured by the BSI-18 and the OTI Health Scale), social situation, drug use, COVID-19 status, and satisfaction with treatment. RESULTS: Out of 84 patients included in the study, 51 participated in both assessments, resulting in a 6-month retention rate of 60.7%. 27.5% were females, and 72.5% were males. The feasibility question of the low-threshold OST clinic can clearly be answered positively. During the course of the study over 6 months, the situation mainly remained stable regarding quality of life, physical and mental health, and days of drug consumption. Patients significantly reduced the time they spent on the drug scene from 8.5 (SD = 7.56) to 6.1 (SD = 6.71) hours a day between the beginning of OST and T2 (p = 0.020). While 56.9% answered to be homeless at the beginning of OST, only 33.3% answered not to have found an accommodation by T2 (p = 0.012). The number of patients having contact to social workers increased from 51.0% to 74.5% (p = 0.004). Almost 2 fifths of the patients took part in PCR testing for COVID-19 (that only being done if they had symptoms), and none of the tests were positive. DISCUSSION/CONCLUSIONS: Overall, the low-threshold OST clinic has been successfully implemented in order to help a vulnerable group of people navigate through a global pandemic and support the public health sector. Further conclusions on effects are limited by the short study period and the small number of patients, which calls for further research studies in a larger setting.

Flexible delivery of opioid agonist treatment during COVID-19 in Norway: qualitative and quantitative findings from an online survey of provider experiences.

BACKGROUND: For patients receiving daily opioid agonist treatment (OAT) for opioid dependence, several countries relaxed treatment guidelines at the beginning of the COVID-19 pandemic. This involved longer take-home intervals for methadone and buprenorphine doses as well as a reduction in supervised dosing and drug screening. To date, little is known about the medium or long-term experience of OAT deregulation. Therefore, we conducted a survey to explore how OAT providers perceived greater flexibility in OAT service delivery at the end of the second year of the pandemic. METHODS: Nationwide cross-sectional study of twenty-three OAT units in 19 publicly funded hospital trusts in Norway. OAT units were sent a 29-item online questionnaire comprising closed-format and open-ended questions on treatment provider experiences and changes in OAT service delivery during the past 12 months (January to December 2021). RESULTS: Twenty-three (of whom female: 14; 60.8%) managers or lead physicians of OAT units completed the questionnaire reporting that, in 2021, most OAT units (91.3%, n = 21) still practiced some adjusted approaches as established in the beginning of the pandemic. The most common adaptions were special protocols for COVID-19 cases (95.7%, n = 22), increased use of telephone- (91.3%, n = 21) and video consultations (87.0%, n = 20), and longer take-home intervals for OAT medications (52.2%, n = 12). The use of depot buprenorphine also increased substantially during the pandemic. According to the OAT providers, most patients handled flexible treatment provision well. In individual cases, patients' substance use was identified as key factor necessitating a reintroduction of supervised dosing and drug screening. Collaboration with general practitioners and municipal health and social services was generally perceived as crucial for successful treatment delivery. CONCLUSIONS: Overall, the Norwegian OAT system proved resilient in the second year of the COVID-19 pandemic, as its healthcare workforce embraced innovation in technology (telemedicine) and drug development (depot buprenorphine). According to our nationally representative sample of OAT providers, most patients were compliant with longer take-home doses of methadone and buprenorphine. Our findings suggest that telemedicine can be useful as adjunct to face-to-face treatment and provide greater flexibility for patients.

People who inject oral morphine favor experimentation with injectable opioid substitution.

BACKGROUND: The French Addictovigilance network has observed the existence of the intravenous use of oral morphine capsules among people suffering from opioid use disorders. According to persons who inject morphine, these capsules are easy to dissolve and then inject, giving them the image of an "injectable" opioid substitution treatment (OST). In France, validated OSTs are only available orally, so dissolving morphine capsules represents the only alternative for patients who are not sufficiently relieved by oral forms. This practice presents risks related to the potential persistence of particles of the oral galenic in the injectable solution, despite its filtration, but also risks-notably of overdose-related to the pharmacological effects of opioids and to variations of the quantities of morphine extracted during the dissolution of the capsules. We conducted an online survey among the people concerned to collect data on their needs and expectations regarding a possible injectable substitution. METHOD: An anonymous online survey including all voluntary respondents residing in France and using oral morphine intravenously was conducted in partnership with the Psychoactif harm reduction organization, from 23/03/2020 to 01/04/2021. RESULTS: The analysis of the 157 exploitable questionnaires showed that 41% of the respondents obtained their drugs only from illegal markets. The others received, regularly or occasionally, medical prescriptions, reimbursed in 84% of cases. For 78% of the respondents, injection was the most frequent route of morphine administration, with 3.8 ± 2 injections per day. 56% of the respondents were receiving an OST, on prescription (79%), monthly (86%), in addition to morphine. Skenan® capsules were the most frequently used (81%) and 47.2% of the respondents had already experienced injection-related complications. 95% of the respondents were in favor of experimenting with an injectable morphine substitution. Those who never received medical prescriptions were the youngest (< 25 years) respondents, they reported only occasional use of morphine, and always intravenously. CONCLUSION: Oral morphine capsules dissolved and injected intravenously are not a safe and sustainable injectable substitution. Respondents wish to be able to benefit from an injectable substitution with a formulation adapted to the intravenous route. The availability of an injectable substitution would facilitate harm reduction and entry into care for the people concerned, particularly the youngest who have never received morphine prescriptions.

Association between oral and general health related quality of life among Norwegian patients with substance use disorders in opioid agonist therapy.

OBJECTIVE: Assess the association between oral and general health related quality of life using oral impacts on daily performances (OIDP) and the quality of life tool EQ-5D-5L from EuroQoL among patients with substance use disorder (SUD) who receive opioid agonist therapy. METHOD: 609 patients with SUD completed the EQ-5D-5L. A dental sub-study of 167 patients completed OIDP and an oral examination when attending outpatient clinics in Western Norway for their opioid agonist therapy. The merged analytical sample consisted of 165 patients. The association between OIDP and EQ-5D-5L was assessed by Spearman's rho and a linear multiple variable regression analysis. A line graph and a Pen's parade displayed the distributions of OIDP sum scores and EQ-5D-5L index values. RESULTS: Overall mean summary- and index EQ-5D-5L scores were 9.97 (sd 3.25) and 0.69 (sd 0.22). Mean score for OIDP was 9.75 (sd 9.59). Spearman's rho was 0.34 (p < .01) between OIDP and EQ-5D-5L summary scores. Linear regression revealed an association adjusted for sex and age of 0.12 (95% CI 0.07-0.17) and a coefficient of determination of 0.1460. CONCLUSION: This study reveals a strong association between OIDP and EQ-5D-5L reflecting the importance of oral health to general health for patients with SUD. Health care professionals should pay attention to oral health. Effective interventions might improve patients' oral and health related quality of life.

The Role of Physical Exercise in Opioid Substitution Therapy: Mechanisms of Sequential Effects.

It is generally accepted that chronic opioid use is associated with structural and functional changes in the human brain that lead to an enhancement of impulsive behavior for immediate satisfaction. Interestingly, in recent years, physical exercise interventions have been used as an adjunctive treatment for patients with opioid use disorders (OUDs). Indeed, exercise has positive effects on both the biological and psychosocial basis of addiction, modifying neural circuits such as the reward, inhibition, and stress systems, and thus causing behavioral changes. This review focuses on the possible mechanisms that contribute to the beneficial effects of exercise on the treatment of OUDs, with emphasis placed on the description of a sequential consolidation of these mechanisms. Exercise is thought to act initially as a factor of internal activation and self-regulation and eventually as a factor of commitment. This approach suggests a sequential (temporal) consolidation of the functions of exercise in favor of gradual disengagement from addiction. Particularly, the sequence in which the exercise-induced mechanisms are consolidated follows the pattern of internal activation-self-regulation-commitment, eventually resulting in stimulation of the endocannabinoid and endogenous opioid systems. Additionally, this is accompanied by modification of molecular and behavioral aspects of opioid addiction. Overall, the neurobiological actions of exercise in combination with certain psychological mechanisms appear to promote its beneficial effects. Given the positive effects of exercise on both physical and mental health, exercise prescription is recommended as a complement to conventional therapy for patients on opioid maintenance treatment.

COVID-19 and substance use disorders: a review of international guidelines for frontline healthcare workers of addiction services.

BACKGROUND: People with substance use disorders may be at a greater risk of contracting COVID-19 infection and developing medical complications. Several institutional and governmental health agencies across the world developed ad hoc guidance for substance use disorder services and care of individuals misusing substances. We aimed to synthesise the best available recommendations on management and care of people with or at risk of substance use disorders during the COVID-19 pandemic from existing guidelines published in UK, USA, Australia, Canada, New Zealand, and Singapore. METHODS: We systematically searched existing guidelines and websites from 28 international institutions and governmental bodies in the context of the COVID-19 pandemic (May 4th 2021). We summarized the extracted data as answers to specific clinical questions. RESULTS: We organised the available recommendations from 19 sources in three sections. First, we focused on general advice and recommendations for people who misuse alcohol or drugs during the COVID-19 pandemic, the design of contingency plans, safeguarding issues for children and families of service users and advice to the public, patients, and carers. Then, we summarised specific guidelines for people who use illicit drugs and related services, such as opioid substitution treatment and needle and syringe programmes. Finally, we provided a synthesis on specific recommendations for services supporting people who misuse alcohol and key topics in the field, such as management of alcohol detoxification and safe transition between supervised and unsupervised consumption. CONCLUSIONS: Available guidance reflected different approaches, ranging from being extremely cautious in providing recommendations other than generic statements to proposing adaptation of previously available guidelines to confront the challenges of the COVID-19 pandemic. After the early phase, guidance focused on reduction of infection transmission and service delivery. Guidance did not provide advice on infection prevention via vaccination programmes and service access strategies tailored to individuals with substance use disorders.

Healthcare utilization for somatic conditions among Swedish patients in opioid substitution treatment, with and without on-site primary healthcare.

BACKGROUND: Opioid substitution treatment (OST) populations are aging and have increased mortality and somatic morbidity compared to general populations internationally. While OST patients have poor self-rated physical health and unmet healthcare needs, documented healthcare utilization has been sparsely investigated. The aim of this study was to assess registered healthcare utilization for somatic conditions in a sample of Swedish OST patients, and compare healthcare utilization among OST patients with and without use of on-site primary healthcare (PHC). METHODS: Patients in OST in Malmö, Sweden, were recruited for a survey study conducted in 2017-2018. Survey data were compared with comprehensive patient records from specialized and primary care during one year prior to study inclusion (total n = 190). All patient records were examined for healthcare utilization, source of healthcare (PHC, emergency care and secondary care), and documented diagnoses and symptoms. Factors associated with healthcare utilization were analyzed by using logistic regression analysis. Patients with and without on-site PHC were compared by using descriptive statistics and Chi-2 test. RESULTS: A total of 88% of the sample had been in direct or indirect contact with somatic healthcare during one year (PHC 66%; emergency care 28%; secondary care 67%). The most prevalent somatic diagnoses were infectious diseases (39%) and symptom diagnoses (37%). Respiratory, dermatological and musculoskeletal diagnoses, and trauma/intoxication were documented in 21-26% of the sample, respectively. PHC utilization was associated with older age and being born in Sweden. Among patients with on-site PHC (n = 25), the number utilizing secondary care was 84%, and certain diagnostic codes were more frequent in this group. CONCLUSION: OST patients are seemingly underserved as regards their physical health. Since increased OST access decreases opioid overdose fatalities, the life expectancy among OST patients is likely to increase and thereby also increases the risk of age-related conditions. Thus, easily accessible physical healthcare is of great importance in this group. On-site PHC might be a way to establish healthcare contact with OST patients, especially for non-acute conditions, although further research is needed.

Hepatitis C treatment uptake among patients who have received methadone substitution treatment in the Republic of Georgia.

OBJECTIVES: There is a dearth of research on hepatitis C virus (HCV) treatment uptake among people who inject drugs (PWIDs) and receive methadone substitution treatment (MST) in Eastern Europe and Central Asia countries. This study contributed to addressing that gap. We examined and identified factors that may affect HCV treatment uptake among PWID who received MST in the Republic of Georgia. STUDY DESIGN: The design of the study is retrospective cohort study. METHODS: We conducted HCV care cascade analysis by matching the data from the web-based national hepatitis C program registry (ELIM C) and the MST treatment database between January 1, 2015, and December 31, 2018. Using the World Health Organization's (WHO) Consensus HCV cascade of care (CoC) global instrument, we assessed the progress made toward the country's 2020 and WHO's 2030 hepatitis C elimination targets for the subpopulation of MST patients. RESULTS: Overall, 10,498 individuals have been dispensed methadone during the study period. A total of 6828 MST beneficiaries had HCV screening, of whom 5843 (85.6%) tested positive; 5476 (93.7%) were tested for HCV viremia, and 5275 (96.3%) were confirmed with chronic HCV infection. More than 75% (n = 4000) of HCV-infected MST patients initiated HCV treatment, and 3772 (94.3%) completed the treatment. Of those eligible for sustained virologic response assessment, 71.0% (2641/3715) were evaluated, and the reported cure rate was 96.1% (2537). The study found the odds of patients starting HCV treatment differed by the type of facility they were screened at and whether they were registered as PWID at the screening sites. The patients screened at centers with integrated HCV treatment services had higher treatment uptake rates than those screened at other centers. CONCLUSIONS: As the cumulative HCV treatment uptake and cure rates among MST patients with HCV infection are high (75.8% and 96.1%, respectively), the MST patients might become the first microelimination target population in which hepatitis C elimination will be achieved in Georgia. The study found the type of screening facility and whether MST patients registered themselves as PWID or not had significant effects on MST patients starting HCV treatment. At the same time, the study did not find gender and age to be significant predictors of MST patients starting HCV treatment. MST patients used different types of health facilities to get screened for HIV. Many of them did not register themselves as PWID when screened for HIV. The existence of only a few harm reduction sites with integrated HCV treatment services, a high level of stigma, and the criminalization of drug use might have incentivized MST patients to self-navigate across the HCV care continuum with the rest of the population. The implementation of focused, harm reduction, integrated HCV treatment with good peer and professional adherence support at treatment sites could help reach the hepatitis C elimination goals among MST patients.

Experience with viral hepatitis C treatment among people who inject drugs and participate in a methadone substitution treatment program.

OBJECTIVES: Long-term monitoring of the mutual effects of chronic viral hepatitis C (VHC) treatment and tailored addiction treatment. In 2016, the World Health Organization (WHO) published an action plan to eliminate viral hepatitis C globally by 2030. People who inject drugs (PWID) are a key population that needs increased attention and care. Two decades before the announcement of the WHO plan for the global elimination of HCV (hepatitis C virus), the Remedis Medical Facility, where the study was conducted, established a “Comprehensive Care Program for patients with substance use disorders and addictive behaviour”. METHODS: We evaluated all patients who were in the methadone program as of 1 March 2020, regardless of OST duration, OST dosage, age or gender. Their epidemiological and demographic data obtained during a structured clinical interview and laboratory test results were analysed. RESULTS: Of 24 patients on methadone substitution therapy, 12 (50%) were anti-HCV negative before starting OST. None of them became newly infected with hepatitis C virus (HCV) during OST. The remaining 12 of the study patients were anti-HCV positive. Ten of them have already undergone successful treatment for viral hepatitis. Two patients were re-infected with HCV. CONCLUSION: The presented work confirms the high efficacy of chronic VHC treatment among PWID in inducing suitable conditions. We consider combination of HCV infection treatment and targeted tailored addiction treatment as a starting point for achieving control over the HCV epidemic in the Czech Republic, with a possible positive impact on other blood-borne infections related to risky behaviour.

Hepatitis C Virus Prevalence and Incidence in a Large Nationwide Sample of Patients in Opioid Substitution Treatment in Germany: A Prospective Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent among people who inject drugs (PWID). Accurate data on HCV prevalence and incidence rates among patients receiving opioid substitution treatment (OST) are needed to estimate the current and future burden of HCV infections in this high-risk population. METHODS: Baseline data from routine care were collected between October 2014 and June 2016 from randomly selected OST facilities in Germany. The primary outcome measure was the HCV status (antibody and RNA prevalence). Patients who were HCV antibody-negative at baseline were followed up after 12 months to calculate the HCV incidence rate. RESULTS: Sixty-three facilities from 14 German Federal States provided clinical data for a total of 2466 OST patients. HCV antibody and HCV RNA prevalence were 58.8% (95% confidence interval [CI], 56.8%-60.8%) and 27.3% (95% CI, 25.5%-29.2%), respectively. At baseline, a total of 528 patients (21.4%) had previously undergone antiviral treatment. Moreover, lower HCV RNA prevalence was associated with female gender, employment, younger age, and shorter duration of OST and opioid dependence. The HCV incidence rate was 2.5 cases per 100 person-years. CONCLUSIONS: The low HCV RNA prevalence and HCV incidence rates confirm that OST in Germany is an effective setting both for treating chronic HCV infections and for preventing new infections among PWID. Scaling up the provision of OST, HCV testing, and HCV treatment among OST patients are important public health strategies for reducing HCV infections in this high-risk population.

Protocol for a multi-site study of the effects of overdose prevention education with naloxone distribution program in Skåne County, Sweden.

BACKGROUND: Continuously high rates of overdose deaths in Sweden led to the decision by the Skåne County to initiate the first regional take-home naloxone program in Sweden. The project aims to study the effect of overdose prevention education and naloxone distribution on overdose mortality in Skåne County. Secondary outcome measures include non-fatal overdoses and overdose-related harm in the general population, as well as cohort-specific effects in study participants regarding overdoses, mortality and retention in naloxone program. METHODS: Implementation of a multi-site train-the-trainer cascade model was launched in June 2018. Twenty four facilities, including opioid substitution treatment units, needle exchange programs and in-patient addiction units were included for the first line of start-up, aspiring to reach a majority of individuals at-risk within the first 6 months. Serving as self-sufficient naloxone hubs, these units provide training, naloxone distribution and study recruitment. During 3 years, questionnaires are obtained from initial training, follow up, every sixth month, and upon refill. Estimated sample size is 2000 subjects. Naloxone distribution rates are reported, by each unit, every 6 months. Medical diagnoses, toxicological raw data and data on mortality and cause of death will be collected from national and regional registers, both for included naloxone recipients and for the general population. Data on vital status and treatment needs will be collected from registers of emergency and prehospital care. DISCUSSION: Despite a growing body of literature on naloxone distribution, studies on population effect on mortality are scarce. Most previous studies and reports have been uncontrolled, thus not being able to link naloxone distribution to survival, in relation to a comparison period. As Swedish registers present the opportunity to monitor individuals and entire populations over time, conditions for conducting systematic follow-ups in the Swedish population are good, serving the opportunity to study the impact of large scale overdose prevention education and naloxone distribution and thus fill the knowledge gap. TRIAL REGISTRATION: Naloxone Treatment in Skåne County - Effect on Drug-related Mortality and Overdose-related Complications, NCT03570099, registered on 26 June 2018.

Dispensation of attention deficit hyperactivity disorder (ADHD) medications in patients receiving opioid agonist therapy; a national prospective cohort study in Norway from 2015 to 2017.

BACKGROUND: It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated. METHODS: Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to assess the associations between ADHD medication, and OAT opioid use, and dispensations of other potentially addictive drugs and DAAs against hepatitis C infection. RESULTS: A total of 9235 OAT patients were included. The proportion of patients who were dispensed ADHD medication increased from 3.5 to 4.6% throughout the study period. The three most dispensed CAS were short- and intermediate-acting methylphenidate (55%), lisdexamphetamine (24%), and dexamphetamine (17%) in 2017. Buprenorphine, rather than methadone, as OAT opioid (adjusted odds ratio: 1.6, CI: 1.2-2.1) was associated with being dispensed ADHD medication. Among patients who received CAS and OAT opioids each calendar year, the dispensed doses of methylphenidate increased from 63 mg/day in 2015 to 76 mg/day in 2017 (p = 0.01). Sixty percent of patients receiving ADHD medications were also dispensed other addictive drugs concomitantly in 2017. Similar results were found in 2015 and 2016. CONCLUSION: Co-prescription of ADHD medications was low among patients on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed.

Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients receiving opioid agonist therapy; a prospective cohort study in Norway from 2013 to 2017.

BACKGROUND: Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients on opioid agonist therapy (OAT) are common and have pros and cons. The objectives of the current study are to define the dispensation rates of these potentially addictive drugs, and whether the number and the mean daily doses of dispensed OAT opioids and discontinuing OAT, are associated with being dispensed benzodiazepines, z-hypnotics and gabapentinoids among patients on OAT in Norway in the period 2013 to 2017. METHODS: Information about all dispensed opioids, benzodiazepines, z-hypnotics and gabapentinoids were recorded from the Norwegian Prescription Database (NorPD). A total of 10,371 OAT patients were included in the study period. The dispensation rates were defined as the number of patients who were dispensed at least one of the potentially addictive drugs divided among the number of patients who have dispensed an OAT opioid per calendar year. Mean daily doses were calculated, and for benzodiazepines and z-hypnotics, stated in diazepam equivalents. The association between dispensed potentially addictive drugs, and the number and the type of dispensed OAT opioids were calculated by using logistic regression models. RESULTS: Half of the OAT patients received at least one dispensation of a benzodiazepine or z-hypnotic, and 11% were dispensed at least a gabapentinoid in 2017. For dispensed benzodiazepines or z-hypnotics, the mean daily dose was reduced from 21 mg (95% confidence interval (CI): 20-23) diazepam equivalents in 2013 to 17 mg (95% CI: 16-17) in 2017. The mean daily dose of pregabalin increased from 365 mg (95% CI: 309-421) in 2013 to 386 mg (95% CI: 349-423) in 2017. Being dispensed a gabapentinoid (adjusted odds ratio (aOR) = 2.5, 95% CI: 2.1-3.0) or a non-OAT opioid (aOR = 3.0, 95% CI: 2.6-3.5) was associated with being dispensed a benzodiazepine or z-hypnotic. Discontinuing OAT did not affect the number of dispensations and the doses of potentially addictive drugs. CONCLUSION: The dispensation rates of potentially addictive drugs are high in the OAT population. Treatment indications, as well as requirements for prescription authority, need to be debated and made explicit. Randomized controlled trials evaluating the benefits and risks of such co-prescription are required.

Too much or too little opioids to patients receiving opioid agonist therapy in Norway (2013-2017): a prospective cohort study.

BACKGROUND: Dispensations of opioid analgesics to patients on opioid agonist therapy (OAT) may increase the risk of overdoses. The current study's objectives are to investigate the dispensation rates and mean daily doses of dispensed opioid analgesics among patients who received OAT opioids in Norway during 2013-2017 and evaluate whether discontinuing OAT opioids affects the dispensed dose of opioid analgesics. METHODS: Information on opioids was collected from the Norwegian Prescription Database. Dispensation rates were calculated by dividing the number of patients who were dispensed at least one opioid analgesic by the number of patients who were dispensed an OAT opioid. We calculated the mean daily dose of opioid analgesics in oral morphine equivalents. The OAT opioid dose was defined as a ratio between the dispensed doses divided by the mean recommended dose. We used logistic regression to estimate the association between the dispensation of an opioid analgesic, a dose of OAT opioids, having chronic pain, and being on palliative care. RESULTS: A total of 10,371 patients were dispensed at least one OAT opioid during the study period. In 2017, 18% were dispensed an opioid analgesic with a mean daily dose of 29 mg of oral morphine equivalents. Being dispensed an opioid analgesic was associated with having chronic pain (adjusted odds ratio (aOR): 3.6, 95% confidence interval: 3.2-4.2), being on palliative care (aOR: 6.1, 4.7-7.9), and receiving an OAT opioid dose below half of the recommended OAT dose (aOR: 1.7, 1.4-2.0). Similar results were seen in 2013-2016. The discontinuation of OAT opioids could increase the dose of dispensed opioid analgesics. CONCLUSION: Reducing the dispensation of opioid analgesics can be achieved by increasing the OAT opioid dose for patients on a low OAT dose, and by extending the period needed to taper off the OAT opioid dose at discontinuation.

Non-prescribed use of methadone and buprenorphine prior to opioid substitution treatment: lifetime prevalence, motives, and drug sources among people with opioid dependence in five Swedish cities.

BACKGROUND: Opioid substitution treatment (OST) with methadone or buprenorphine is the most effective means of treating opioid dependence. If these substances are used by people who are not undergoing OST, they can however carry serious risks. This article examines the lifetime prevalence, motives, and drug sources for such use, as well as geographical differences in these variables. METHODS: Structured interviews were conducted with 411 patients from 11 OST clinics in five Swedish cities. The researchers carried out 280 interviews on-site, while 131 interviews were conducted by specially trained patients through privileged access interviewing. Data were analyzed by frequency and average calculations, cross-tabulations, and χ2 tests. RESULTS: The lifetime prevalence of non-prescribed use was 87.8% for methadone, 80.5% for buprenorphine, and 50.6% for buprenorphine/naloxone. Pseudo-therapeutic motives-avoiding withdrawal symptoms, staying clean from heroin, detoxification, or taking care of one's own OST-were commonly cited as driving the use, while using the drugs for euphoric purposes was a less common motive. Most respondents had bought or received the substances from patients in OST, but dealers were also a significant source of non-prescribed methadone and buprenorphine. Geographical differences of use, motives, and sources suggest that prescription practices in OST have a great impact on which substances are used outside of the treatment. CONCLUSIONS: Experiences of non-prescribed use of methadone and buprenorphine are extremely common among those in OST in southern Sweden. As the use is typically driven by pseudo-therapeutic motives, increased access to OST might decrease the illicit demand for these substances. Buprenorphine/naloxone has a lower abuse potential than buprenorphine and should therefore be prioritized as the prescribed drug. Supervised dosage and other control measures are important provisions in the prevention of drug diversion and non-prescribed use among people not undergoing OST.

Incidence and Risk Factors for Hepatitis C Virus Infection among Illicit Drug Users in Italy.

So far, only three small outdated studies have investigated hepatitis C virus (HCV) incidence and risk factors among illicit drug users (DUs) in Italy. Thus, during 2007-2010, we conducted a prospective cohort study among DUs attending 17 Italian rehabilitation centers serving urban areas. Two hundred eighty-four HCV-uninfected DUs were prospectively followed by interview and anti-HCV antibody and RNA testing every 6 months. Incidence was calculated using the person-years method. Infection predictors were assessed by time-dependent Cox analysis. Participants were mostly male (83.4%), under opioid substitution therapy (OST) (78.9%), non-injecting DUs (67.9%), and with a mean age of 30.8. Ninety-one of 224 DUs initially under OST interrupted treatment during the follow-up. Overall HCV incidence was 5.83/100 person-years at risk (PYAR) [95% confidence intervals (CI), 3.63-9.38]. The incidence did not significantly differ according the participants' sociodemographic characteristics or the degree of urbanization of the towns involved in the study. The incidence was higher for DUs under than for those not under OST (6.23 vs 4.50/100 PYAR; p = 0.681). Incidence was also higher for those with than for those without OST interruption (7.17 vs 5.04/100 PYAR; p = 0.55). However, all these differences were non-significant. At last follow-up visit, a significant decrease in frequency of sharing equipment for preparation/using drugs (by injection or not) was observed by analyzing either the whole cohort or DUs under OST only. Anti-HCV seroconversion resulted independently associated with sharing drug preparation/use equipment, backloading, having a HCV-positive sexual partner, or household and (marginally) intravenous injection. In this study, HCV incidence was non-negligible and OST seemed to lack effectiveness in reducing it. In Italy, implementation of combined harm reduction interventions and antiviral treatment of chronically infected DUs would be needed.