Building Capacity for Injectable Diacetylmorphine and Hydromorphone for the Treatment of Opioid Use Disorder: Identifying Typical Doses.

Identifying typical doses of existing opioid use disorder medications, such as injectable opioid agonist treatment (iOAT), can support client and program needs, and potentially increase iOAT expansion. Longitudinal data from participants in a cohort study (n = 131), along with clinic dispensation records from August 2014 to April 2020, were used to examine physician prescribed as well as used doses of injectable diacetylmorphine and hydromorphone. Dosage groups, by medication and prescribed dose per session, were created for both hydromorphone and diacetylmorphine. A total of 534, 522 injections were registered during the study period among 129 participants. Mean received diacetylmorphine doses ranged from 106 to 989 mg per day, with most clients using 125-262 mg per session (mean 192.99 mg) and attending 2.40 sessions per day. Mean received hydromorphone doses ranged from 51.09 to 696.06 mg per day, with the majority using 88-154 mg per session (mean 121.32 mg; 2.43 sessions). Average daily doses remained stable overtime and, while mid-range doses were most typical, participants used the whole spectrum of allowable dose prescriptions. Evidence supporting typical doses of iOAT can be integrated into program planning to better allow providers and prescribers to anticipate program needs and engage in individualized care.

Shared decision-making and client-reported dose satisfaction in a longitudinal cohort receiving injectable opioid agonist treatment (iOAT).

BACKGROUND: Across different types of oral Opioid Agonist Treatment for people with Opioid Use Disorder, receiving a dose that meets their needs is associated with better outcomes. Evidence also shows patients are more likely to receive an "adequate dose" when their prescribers are involving them in decision making. Neither of these findings have been studied in the context of injectable Opioid Agonist Treatment, which is the purpose of this study. METHODS: This study was a retrospective analysis of an 18-month prospective longitudinal cohort study of 131 people receiving injectable Opioid Agonist Treatment. In the 18-month study, observations were collected every two months for one year, and then once more at 18 months. At 6 months, participants were asked whether their dose was satisfactory to them (outcome variable). Generalized Estimating Equations were used, to account for multiple observations from each participant. The final multivariate model was built using a stepwise approach. RESULTS: Five hundred forty-five participant-observations were included in the analysis. Participant-observations were grouped by "dose is satisfactory" and "wants higher dose". From unadjusted analyses, participants were less likely to report being satisfied with their dose if they: were Indigenous, had worse psychological or physical health problems, had ever attempted suicide, were younger when they first injected any drug, were a current smoker, felt troubled by drug problems, gave their medication a lower "drug liking" score, and felt that their doctor was not including them in decisions the way they wanted to be. In the final multivariate model, all previously significant associations except for "current smoker" and "troubled by drug problems" were no longer significant after the addition of the "drug liking" score. CONCLUSIONS: Patients in injectable Opioid Agonist Treatment who are not satisfied with their dose are more likely to: be troubled by drug problems, be a current smoker, and report liking their medication less than dose-satisfied patients. Prescribers' practicing shared decision-making can help patients achieve dose-satisfaction and possibly alleviate troubles from drug problems. Additionally, receiving a satisfactory dose may be dependent on patients being able to access an opioid agonist medication (and formulation) that they like.

"It feels like I'm coming to a friend's house": an interpretive descriptive study of an integrated care site offering iOAT (Dr. Peter Centre).

BACKGROUND: Injectable opioid agonist treatment (iOAT) has proven to be a safe and effective treatment option for severe opioid use disorder (OUD). Yet, iOAT is often isolated from other health and social services. To align with a person-centered care approach, iOAT can be embedded in sites that combine systems and services that have been historically fragmented and that address multiple comorbidities (integrated care sites). The present study investigates the addition of iOAT at an integrated care in Vancouver, British Columbia. We aimed to capture what it means for service users and service providers to incorporate iOAT in an integrated care site and describe the processes by which the site keeps people engaged. METHODS: We conducted 22 interviews with 15 service users and 14 interviews with 13 service providers across two rounds of individual semi-structured interviews (Fall 2021, Summer 2022). The second interview round was precipitated by a service interruption in medication dispensation. Interview audio was recorded, transcribed, and then analysed in NVivo 1.6 following an interpretive description approach. RESULTS: The emergent themes from the analysis are represented in two categories: (1) a holistic approach (client autonomy, de-medicalized care, supportive staff relationships, multiple opportunities for engagement, barriers to iOAT integration) and (2) a sense of place (physical location, social connection and community belonging, food). CONCLUSION: Incorporating iOAT at an integrated care site revealed how iOAT delivery can be strengthened through its direct connection to a diverse, comprehensive network of health and social services that are provided in a community atmosphere with high quality therapeutic relationships.

The Impact of Injectable Opioid Agonist Treatment (iOAT) on Involvement in Criminalized Activities: A Secondary Analysis from a Clinical Trial in Vancouver, BC.

Purpose: A significant portion of the economic consequences of untreated Opioid Use Disorder (OUD) relate to individuals' involvement in the criminal justice system. The present study uncovers if treatment with iOAT is related to the number of criminal charges amongst participants, what type of crime participants were involved in, and the frequency with which participants were victims of crime. This study contributes to the body of research on the effectiveness of iOAT reducing criminal involvement. Patients and Methods: This is a secondary analysis of police record data obtained from the Vancouver Police Department over a three-year period during the Study to Assess Longer-term Opioid Medication Effectiveness clinical trial. The data was obtained from participants (N = 192) enrolled in the trial through a release of information form. Results: During the three-year period, most charges (45.6%) were property offences, and 25.5% of participants were victims of crime. Participants with no treatment prior to randomization into the SALOME trial were 2.61 (95% CI = 1.64-4.14) more likely to have been charged with a crime than during the iOAT state. Conclusion: IOAT can reduce individuals' involvement with the criminal justice system and is thus a crucial part of the continuum of care. Addiction should be conceptualized as a healthcare rather than criminal issue.

The impact of relaxing restrictions on take-home doses during the COVID-19 pandemic on program effectiveness and client experiences in opioid agonist treatment: a mixed methods systematic review.

BACKGROUND: The COVID-19 pandemic led to an unprecedented relaxation of restrictions on take-home doses in opioid agonist treatment (OAT). We conducted a mixed methods systematic review to explore the impact of these changes on program effectiveness and client experiences in OAT. METHODS: The protocol for this review was registered in PROSPERO (CRD42022352310). From Aug.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, Cochrane Register of Controlled Trials, and the grey literature. We included studies reporting quantitative measures of retention in treatment, illicit substance use, overdose, client health, quality of life, or treatment satisfaction or using qualitative methods to examine client experiences with take-home doses during the pandemic. We critically appraised studies using the Mixed Methods Appraisal Tool. We synthesized quantitative data using vote-counting by direction of effect and presented the results in harvest plots. Qualitative data were analyzed using thematic synthesis. We used a convergent segregated approach to integrate quantitative and qualitative findings. RESULTS: Forty studies were included. Most were from North America (23/40) or the United Kingdom (9/40). The quantitative synthesis was limited by potential for confounding, but suggested an association between take-home doses and increased retention in treatment. There was no evidence of an association between take-home doses and illicit substance use or overdose. Qualitative findings indicated that take-home doses reduced clients' exposure to unregulated substances and stigma and minimized work/treatment conflicts. Though some clients reported challenges with managing their medication, the dominant narrative was one of appreciation, reduced anxiety, and a renewed sense of agency and identity. The integrated analysis suggested reduced treatment burden as an explanation for improved retention and revealed variation in individual relationships between take-home doses and illicit substance use. We identified a critical gap in quantitative measures of patient-important outcomes. CONCLUSION: The relaxation of restrictions on take-home doses was associated with improved client experience and retention in OAT. We found no evidence of an association with illicit substance use or overdose, despite the expansion of take-home doses to previously ineligible groups. Including patient-important outcome measures in policy, program development, and treatment planning is essential to ensuring that decisions around take-home doses accurately reflect their value to clients.

The mobilization of nurse-client therapeutic relationships in injectable opioid agonist treatment: Autonomy, advocacy and action.

INTRODUCTION: Injectable opioid agonist treatment (iOAT) is an evidence-based treatment that serves an important minority of people with opioid use disorder who require specialized care. Unique to iOAT care is the consistency with which clients access treatment (up to three times daily), a condition that creates repeated opportunities for health care engagement. To date, no study has examined therapeutic relationships in this life saving, nurse-led treatment that can have lasting implications in the equitable delivery of other forms of addictions care. METHODS: This study used grounded theory to generate a dynamic framework for therapeutic relationship building in iOAT. Researchers collected semi-structured interviews from registered nurses working in iOAT sites (n=24) form January 2020 through June 2022. The study analyzed collected data through a constant comparative analysis; explored through open, axial, and selective coding; and assessed in a conditional relationship matrix. The team reviewed key findings with stakeholders through formalized processes of engagement to confirm saturation of coding categories. Throughout data collection and analysis, researchers integrated feedback from additional knowledge users and member checking. Reported findings adhered to the COREQ1 standardized checklist. RESULTS: We identified five interrelated categories that created a distinct culture of care for iOAT nurses: Ways of Knowing, Personal Investment, Leveraging Empathy, Finding Flexibility, and Collaborating to Overcome. Through creating a safe, nonjudgmental environment, nurses establish therapeutic relationships that build trust to identify client needs outside of medication administration. In turn, nurses participate in team-based problem solving to advocate for client needs. If nurses cannot find flexibility within and outside of the health care system to improve client engagement, tensions can arise and therapeutic relationships can be strained. CONCLUSIONS: Therapeutic relationships are an integral part of building and maintaining trust with a population that has been precariously involved with other forms of health care. Nurses make a substantial effort to create a safe and nonjudgmental environment to manifest a culture of care that bridges client needs and program access. Without the expansion of access to iOAT programs and their embedded services, nurses are limited in their ability to provide individualized care for clients with diverse needs.

Changes in daily dose in open-label compared to double-blind: The role of clients' expectations in injectable opioid agonist treatment.

Introduction: Though double-blind studies have indicated that hydromorphone and diacetylmorphine produce similar effects when administered through injectable opioid agonist treatment (iOAT) programs, participant preference may influence some aspects of medication dispensation such as dose. Methods:  This is a retrospective longitudinal analysis. Participants (n = 131) were previously enrolled in a double-blind clinical trial for iOAT who continued to receive treatment in an open-label follow up study. Data included medication dispensation records from 2012 to 2020. Using linear regression and paired t-tests, average daily dose totals of hydromorphone and diacetylmorphine were examined comparatively between double-blind and open-label periods. A subgroup analysis explored dose difference by preference using the proxy, blinding guess, a variable used to facilitate the measurement of treatment masking during the clinical trial by asking which medication the participant thought they received. Results: During the open-label period, participants prescribed diacetylmorphine received 49.5 mg less than during the double-blind period (95% CI -12.6,-86.4). Participants receiving hydromorphone did not see a significant dose decrease. Participants who guessed they received hydromorphone during the clinical trial, but learned they were on diacetylmorphine during the open-label period, saw a decrease in total daily dose of 78.3 mg less (95% CI -134.3,-22.4) during the open-label period. Conclusion: If client preference is considered in the treatment of chronic opioid use disorder, clients may be able to better moderate their dose to suit their individual needs. Together with their healthcare providers, clients can participate in their treatment trajectories collaboratively to optimize client outcomes and promote person-centered treatment options.

Provider experiences with relaxing restrictions on take-home medications for opioid use disorder during the COVID-19 pandemic: A qualitative systematic review.

BACKGROUND: Historical restrictions on take-home medications for opioid use disorder have generated considerable debate. The COVID-19 pandemic shifted the perceived risks and benefits of daily clinic attendance and led to widespread policy reform, creating an unprecedented opportunity to explore the impact of more flexible prescribing. We conducted a qualitative systematic review to synthesize the evidence on providers' experiences with relaxing restrictions on take-home doses of medications prescribed for opioid use disorder during the COVID-19 pandemic. METHODS: The protocol for this systematic review was registered in PROSPERO (CRD42022360589; https://www.crd.york.ac.uk/prospero/). From Sept.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, the Cochrane Register of Controlled Trials, and the grey literature from 2020 onward. Studies were eligible for inclusion if they used qualitative methods to investigate providers' experiences with relaxed restrictions on take-home medications for opioid use disorder during the COVID-19 pandemic. We appraised study quality using the CASP qualitative checklist and used thematic synthesis and GRADE-CERQual to synthesize the results. RESULTS: We retrieved 13 articles representing 11 studies. Six were conducted in the United States and most focused on changes to methadone treatment. Providers' experiences with increased flexibilities around take-homes were broadly positive, despite widespread initial concern over client safety and the potential for medication misuse. For a small number of providers, concerns about diversion were a specific manifestation of more general unease with loss of control over clients and the treatment process. Most providers appreciated increased flexibilities and described them as enabling more individualized, person-centered care. CONCLUSION: Our findings support the continuation of flexibilities around take-homes and demonstrate that regulations and policies that reduce flexibility around take-homes conflict with person-centered approaches to care. Stronger guidance and support from professional regulatory agencies may help increase uptake of flexibilities around take-homes.

Clients' experiences on North America's first take-home injectable opioid agonist treatment (iOAT) program: a qualitative study.

BACKGROUND: To support public health measures during the COVID-19 pandemic, oral opioid agonist treatment (OAT) take-home doses were expanded in Western countries with positive results. Injectable OAT (iOAT) take-home doses were previously not an eligible option, and were made available for the first time in several sites to align with public health measures. Building upon these temporary risk-mitigating guidelines, a clinic in Vancouver, BC continued to offer two of a possible three daily doses of take-home injectable medications to eligible clients. The present study explores the processes through which take-home iOAT doses impacted clients' quality of life and continuity of care in real-life settings. METHODS: Three rounds of semi-structured qualitative interviews were conducted over a period of seventeen months beginning in July 2021 with eleven participants receiving iOAT take-home doses at a community clinic in Vancouver, British Columbia. Interviews followed a topic guide that evolved iteratively in response to emerging lines of inquiry. Interviews were recorded, transcribed, and then coded using NVivo 1.6 using an interpretive description approach. RESULTS: Participants reported that take-home doses granted them the freedom away from the clinic to have daily routines, form plans, and enjoy unstructured time. Participants appreciated the greater privacy, accessibility, and ability to engage in paid work. Furthermore, participants enjoyed greater autonomy to manage their medication and level of engagement with the clinic. These factors contributed to greater quality of life and continuity of care. Participants shared that their dose was too essential to divert and that they felt safe transporting and administering their medication off-site. In the future, all participants would like more accessible treatment such as access longer take-home prescriptions (e.g., one week), the ability to pick-up at different and convenient locations (e.g., community pharmacies), and a medication delivery service. CONCLUSIONS: Reducing the number of daily onsite injections from two or three to only one revealed the diversity of rich and nuanced needs that added flexibility and accessibility in iOAT can meet. Actions such as licencing diverse opioid medications/formulations, medication pick-up at community pharmacies, and a community of practice that supports clinical decisions are necessary to increase take-home iOAT accessibility.

"As long as that place stays open, I'll stay alive": Accessing injectable opioid agonist treatment during dual public health crises.

BACKGROUND: Since the onset of the COVID-19 pandemic, overdose rates in North America have continued to rise, with more than 100,000 drug poisoning deaths in the past year. Amidst an increasingly toxic drug supply, the pandemic disrupted essential substance use treatment and harm reduction services that reduce overdose risk for people who use drugs. In British Columbia, one such treatment is injectable opioid agonist treatment (iOAT), the supervised dispensation of injectable hydromorphone or diacetylmorphine for people with opioid use disorder. While evidence has shown iOAT to be safe and effective, it is intensive and highly regimented, characterized by daily clinic visits and provider-client interaction-treatment components made difficult by the pandemic. METHODS: Between April 2020 and February 2021, we conducted 51 interviews with 18 iOAT clients and two clinic nurses to understand how the pandemic shaped iOAT access and treatment experiences. To analyze interview data, we employed a multi-step, flexible coding strategy, an iterative and abductive approach to analysis, using NVivo software. RESULTS: Qualitative analysis revealed the ways in which the pandemic shaped clients' lives and the provision of iOAT care. First, client narratives illuminated how the pandemic reinforced existing inequities. For example, socioeconomically marginalized clients expressed concerns around their financial stability and economic impacts on their communities. Second, clients with health comorbidities recognized how the pandemic amplified health risks, through potential COVID-19 exposure or by limiting social connection and mental health supports. Third, clients described how the pandemic changed their engagement with the iOAT clinic and medication. For instance, clients noted that physical distancing guidelines and occupancy limits reduced opportunities for social connection with staff and other iOAT clients. However, pandemic policies also created opportunities to adapt treatment in ways that increased patient trust and autonomy, for example through more flexible medication regimens and take-home oral doses. CONCLUSION: Participant narratives underscored the unequal distribution of pandemic impacts for people who use drugs but also highlighted opportunities for more flexible, patient-centered treatment approaches. Across treatment settings, pandemic-era changes that increase client autonomy and ensure equitable access to care are to be continued and expanded, beyond the duration of the pandemic.

Measuring the preferences of injectable opioid agonist treatment (iOAT) clients: Development of a person-centered scale (best-worst scaling).

BACKGROUND: Injectable opioid agonist treatment (iOAT) is effective for opioid use disorder (OUD), yet little is known about client preferences for accessing iOAT (e.g., with diacetylmorphine, hydromorphone, buprenorphine, fentanyl, etc.). Best-worst scaling (BWS) is a preference elicitation method from health economics that has never been applied to addiction care broadly, or iOAT specifically. We describe the stages of developing a BWS scale that assesses iOAT clients' treatment delivery preferences to inform program planning and maximize healthcare efficiency. METHODS: We underwent several steps to reveal the relevant attributes/levels and design the scale structure. An initial list of potential attributes and levels was established from a literature review and prior qualitative data. Then, we conducted semi-structured interviews and focus groups with clients (n=21) on their iOAT preferences to confirm the attributes and prioritize/include new ones. Next, we conducted semi-structured interviews and focus groups with iOAT experts and stakeholders to receive their input on the draft list of attributes and levels. A BWS profile case design was piloted with iOAT clients (n=18) from different sites during a think aloud interview. After several rounds of revisions, the final version was tested by iOAT clients (n=2) before the scale was launched. RESULTS: We developed a person-centered scale that assesses current and former iOAT clients' most and least wanted aspects of iOAT delivery. The final version yielded 7 unique attributes: choice of medication, choice of dose, convenience, location & space, scheduling & routines, staff & training, and types of services offered. CONCLUSION: This scale can help expand iOAT programs in a way that is person-centered, rapid, and affordable. The methodology is a guide for other regions with similar populations who aim to develop strong quantitative methodologies that prioritize client collaboration.

Feasibility of Testing Client Preferences for Accessing Injectable Opioid Agonist Treatment (iOAT): A Pilot Study.

Purpose: Injectable opioid agonist treatment (iOAT) is an effective treatment for opioid use disorder (OUD). To our knowledge, no research has systematically studied client preferences for accessing iOAT. Incorporating preferences could help meet the heterogenous needs of clients and make addiction care more person-centred. This paper presents a pilot study of a best-worst scaling (BWS) preference elicitation survey that aimed to assess if the survey was feasible and accessible for our population and to test that the survey could gather sound data that would suit our planned analyses. Patients and Methods: Current and former iOAT clients (n = 18) completed a BWS survey supported by an interviewer using a think-aloud approach. The survey was administered on PowerPoint, and responses and contextual field notes were recorded manually. Think-aloud audio was recorded on Audacity. Results: Clients' feedback fell into five categories: framing of the task, accessibility, conceptualization of attributes and levels, formatting, and behaviour predicting questions. Survey repetitiveness was the most consistent feedback. The data simulation showed that 100 responses should provide an adequate sample size. Conclusion: This pilot demonstrates the type of analysis that can be done with BWS in our population, suggests that such analysis is feasible, and highlights the importance of the interviewer and participant working side-by-side throughout the task.

A multi-methods and longitudinal study of patients' perceptions in injectable opioid agonist treatment: Implications for advancing patient-centered methodologies in substance use research.

BACKGROUND: Patients' perceptions are vital to the delivery and evaluation of substance use treatment. They are most frequently collected at one time-point and measured using patient satisfaction questionnaires or qualitative methodologies. Interestingly, the findings of these studies often diverge, as satisfaction scores tend to be highly positive, while qualitative findings suggest dissatisfaction and areas for improvement. This divergence limits current understandings of patients' perceptions and their potential change over time in treatment. OBJECTIVE: This study explores the relationship between open-ended positive and negative perceptions of treatment and patient satisfaction scores over time. METHODS: The RUTH (Research on the Utilization of Therapeutic Hydromorphone) prospective cohort study included 131 participants receiving injectable diacetylmorphine or hydromorphone in Canada's first injectable opioid agonist treatment (iOAT) program. The study collected the Client Satisfaction Questionnaire (CSQ-8) at eight time-points over an 18-month period. Following a multi-methods approach, the study complemented the CSQ-8 with open-ended positive and negative comments of iOAT. The research team analyzed these comments thematically at each time-point to develop positive and negative perception themes. We then used growth curve modeling to explore the relationship between positive and negative perception themes and patient satisfaction over time. FINDINGS: Over the eight time-points, six positive and eight negative perception themes emerged, broadly reflecting structural (e.g., expansion of iOAT), process (e.g., schedules), relational (e.g., interactions with providers), and outcome-related (e.g., met/unmet needs) perceptions of iOAT. On average, participants reported high satisfaction (grand mean = 29.2 out of 32), and scores did not significantly change over time. However, we did find significant unexplained variation within participants in their satisfaction trajectories and between participants in their initial satisfaction scores. In conditional growth curve models, the theme "unfavorable interactions with providers" had the strongest independent effect on overall satisfaction trajectories. CONCLUSIONS: This study provides an example of how open-ended comments can be integrated with patient satisfaction questionnaire data to gather a comprehensive and patient-centered evaluation of substance use treatment. Considering the iOAT context specifically, relational dynamics and daily treatment access were significant predictors of patient satisfaction over time and may be attributes of iOAT that require further investigation.

Exploring the effectiveness of dextroamphetamine for the treatment of stimulant use disorder: a qualitative study with patients receiving injectable opioid agonist treatment.

BACKGROUND: A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has been associated with higher rates of continued illicit opioid use and treatment dropout. A recent randomized controlled trial demonstrated the effectiveness of dextroamphetamine (a prescribed stimulant) at reducing craving for and use of cocaine among patients receiving injectable opioid agonist treatment. Following this evidence, dextroamphetamine has been prescribed to patients with stimulant use disorder at a clinic in Vancouver. This study investigates perceptions of the effectiveness of dextroamphetamine from the perspective of these patients. METHODS: Data were collected using small focus groups and one-on-one interviews with patients who were currently or formerly receiving dextroamphetamine (n = 20). Thematic analysis was conducted using an iterative approach, moving between data collection and analysis to search for patterns in the data across transcripts. This process led to the defining and naming of three central themes responding to the research question. RESULTS: Participants reported a range of stimulant use types, including cocaine (n = 8), methamphetamine (n = 8), or both (n = 4). Three central themes were identified as relating to participants' perceptions of the effectiveness of the medication: 1) achieving a substitution effect (i.e. extent to which dextroamphetamine provided a substitution for the effect they received from use of illicit stimulants); 2) Reaching a preferred dose (i.e. speed of titration and effect of the dose received); and 3) Ease of medication access (i.e. preference for take home doses (i.e. carries) vs. medication integrated into care at the clinic). CONCLUSION: In the context of continued investigation of pharmacological treatments for stimulant use disorder, the present study has highlighted how the study of clinical outcomes could be extended to account for factors that contribute to perceptions of effectiveness from the perspective of patients. In practice, elements of treatment delivery (e.g. dosing and dispensation protocols) can be adjusted to allow for various scenarios (e.g. on site vs. take home dosing) by which dextroamphetamine and other pharmacological stimulants could be implemented to provide "effective" treatment for people with a wide range of treatment goals and needs.

The suitability of oral diacetylmorphine in treatment-refractory patients with heroin dependence: A scoping review.

OBJECTIVE: To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence. METHODS: The PubMed, Embase, Web of Science and PsycINFO databases were searched. Eleven published studies were identified and selected based on defined eligibility and exclusion criteria. RESULTS: Four pharmacokinetic studies reported negligible plasma concentrations of diacetylmorphine and its active metabolite 6-monacetylmorphine. Among six pharmacodynamic studies, three trials showed that oral diacetylmorphine reduced opioid withdrawal symptoms, one open-label pilot study reported that two patients experienced a modest 'rush' after oral diacetylmorphine and two studies found that patients could not distinguish between oral diacetylmorphine, methadone, or morphine. Regarding the clinical studies, a Swiss prospective cohort study in patients with heroin dependence showed high retention rates of oral diacetylmorphine treatment with few serious adverse events, whereas in the Canadian SALOME trial, oral diacetylmorphine treatment was prematurely discontinued because treatment retention of oral diacetylmorphine was lower than injectable diacetylmorphine maintenance treatment. Finally, two case studies illustrate the limitations and potential problems of oral diacetylmorphine in the treatment of treatment-refractory heroin dependent patients. CONCLUSIONS: Based on all published data, it is unlikely that oral diacetylmorphine produces a substantial 'rush'. Prescription of oral diacetylmorphine might therefore be effective only for treatment-refractory patients with heroin dependence (i) as maintenance treatment for those who never injected or inhaled opioids; (ii) as maintenance treatment for those who want to switch from injection to oral administration of diacetylmorphine; and/or (iii) to reduce opioid withdrawal symptoms.

Use of sustained release dextroamphetamine for the treatment of stimulant use disorder in the setting of injectable opioid agonist treatment in Canada: a case report.

BACKGROUND: For people with opioid use disorder who are not responding to oral opioid agonist treatment, evidence supports the effectiveness of injectable opioid agonist treatment with injectable hydromorphone (an opioid analgesic) and diacetylmorphine (pharmaceutical grade heroin). While this treatment is effective at reducing illicit opioid use, concurrent cocaine use is prevalent. Dextroamphetamine (a central nervous system stimulant) has been found to be a safe and effective treatment for cocaine dependence among people receiving injectable opioid agonist treatment in Europe. We present the first report of dextroamphetamine prescribing offered for the treatment of stimulant use disorder among a patient receiving iOAT outside of a clinical trial. This case report can be used to inform clinical practice in the treatment of cocaine use disorder, an area where interventions are currently lacking. CASE PRESENTATION: Dextroamphetamine was prescribed to a 51-year-old male who was diagnosed with concurrent opioid and stimulant use disorder in an injectable opioid agonist treatment clinic in Vancouver, Canada. He reported smoking crack cocaine daily for more than two decades and was experiencing health consequences associated with this use. He presented to his routine physician visit with the goal of reducing his cocaine use and was prescribed dextroamphetamine for the treatment of stimulant use disorder. After 4-weeks the patient was tolerating the medication with no observed adverse events and was achieving his therapeutic goal of reducing his cocaine use. CONCLUSIONS: Dextroamphetamine can be prescribed to support patients with stimulant use disorder to reduce or stop their use of cocaine. The case demonstrated that when dextroamphetamine was prescribed, a significant reduction in cocaine use was experienced among a patient that had been regularly using cocaine on a daily basis for many years. Daily contact with care for the opioid medication promoted adherence to the stimulant medication and allowed for monitoring of dose and tolerance. Settings where patients are in regular contact with care such as oral and injectable opioid agonist treatment clinics serve as a suitable location to integrate dextroamphetamine prescribing for patients that use illicit stimulants to reduce use and associated harms.

Take home injectable opioids for opioid use disorder during and after the COVID-19 Pandemic is in urgent need: a case study.

BACKGROUND: In North America the opioid poisoning crisis currently faces the unprecedented challenges brought by the COVID-19 pandemic, further straining people and communities already facing structural and individual vulnerabilities. People with opioid use disorder (OUD) are facing unique challenges in response to COVID-19, such as not being able to adopt best practices (e.g., physical distancing) if they're financially insecure or living in shelters (or homeless). They also have other medical conditions that make them more likely to be immunocompromised and at risk of developing COVID-19. In response to the COVID-19 public health emergency, national and provincial regulatory bodies introduced guidance and exemptions to mitigate the spread of the virus. Among them, clinical guidance for prescribers were issued to allow take home opioid medications for opioid agonist treatment (OAT). Take Home for injectable opioid agonist treatment (iOAT) is only considered within a restrictive regulatory structure, specific to the pandemic. Nevertheless, this risk mitigation guidance allowed carries, mostly daily dispensed, to a population that would not have access to it prior to the pandemic. In this case it is presented and discussed that if a carry was possible during the pandemic, then the carry could continue post COVID-19 to address a gap in our approach to individualize care for people with OUD receiving iOAT. CASE PRESENTATION: Here we present the first case of a patient in Canada with long-term OUD that received take home injectable diacetylmorphine to self-isolate in an approved site after being diagnosed with COVID-19 during a visit to the emergency room where he was diagnosed with cellulitis and admitted to receive antibiotics. CONCLUSION: In the present case we demonstrated that it is feasible to provide iOAT outside the community clinic with no apparent negative consequences. Improving upon and making permanent these recently introduced risk mitigating guidance during COVID-19, have the potential not just to protect during the pandemic, but also to address long-overdue barriers to access evidence-based care in addiction treatment.

Longitudinal patterns of cocaine use among patients receiving injectable hydromorphone or diacetylmorphine for the treatment of opioid use disorder: A growth curve modeling approach.

BACKGROUND AND AIMS: Cocaine use is prevalent among people receiving injectable opioid agonist treatment. Investigations of cocaine use in this population have been descriptive and the potential heterogeneity existing in patterns of use have not been characterized. As such, among patients receiving injectable opioid agonist treatment, this study aimed to: 1) quantify intra- and inter-individual variation in cocaine use over 24-months and; 2) determine how predictors of interest explained this variation. METHODS: Participants were patients receiving injectable opioid agonist treatment for opioid use disorder. Study visits were completed at baseline prior to receiving treatment, and 3,6,9,12,18, and 24 months after baseline. A multi-level regression approach to growth curve modeling was employed to estimate and explain intra- (within-person) and inter-individual (between-person) variation in cocaine use. RESULTS: Significant intra and inter-individual variation in cocaine use was identified over 24-months. Treatment engagement was on average associated with reductions in the prior month number of days of cocaine use (range: 0-30)(Estimate (standard error): -0.05(0.02), p = 0.003). On average, men reported less cocaine use compared to women (Estimate (standard error): -5.91(1.57), p=<0.001), and participants reporting ever regularly using cocaine at baseline reported more cocaine use over 24-months compared to participants reporting never regularly using cocaine (Estimate (standard error): 4.72 (1.91), p = 0.013). CONCLUSIONS: Significant reductions in cocaine use were observed and significant heterogeneity in patterns of cocaine use was identified. These heterogeneous cocaine use profiles suggest that an individualized approach to care will be critical in responding to patients' cocaine use in injectable opioid agonist treatment.

Self-managing illicit stimulant use: A qualitative study with patients receiving injectable opioid agonist treatment.

INTRODUCTION AND AIMS: Illicit stimulant use is prevalent among patients receiving injectable opioid agonist treatment (iOAT) and has been associated with early treatment discontinuation and illicit opioid use. Despite these concerns, little is known about the use of illicit stimulants in this population. As such, this study aimed to explore the processes by which patients receiving iOAT engage in the use of illicit stimulants. DESIGN AND METHODS: One-on-one in-depth qualitative interviews were conducted. Data collection and analysis followed an iterative approach of coding, searching for meaning, and returning to data collection to saturate categories and explicate relationships between them. Participants were patients receiving iOAT in Vancouver, Canada that reported the use of illicit stimulants (n = 31). RESULTS: The process of 'self-managing illicit stimulant use' was constructed from the data. This process was made up of three interrelated categories reflecting participants' engagement in illicit stimulant use: (i) distancing from the street environment; (ii) taking control of use; and (iii) mobilising support (clinical and social). DISCUSSION AND CONCLUSIONS: For patients with opioid use disorder and concurrent stimulant use disorder, access to iOAT can promote the self-management of illicit stimulant use. Daily visits to the clinic for opioid agonist treatment present an important opportunity to offer services and supports for patients who use illicit stimulants. Interventions can be guided by patients, recognising them as experts in the management of their stimulant use.