Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Activism and scientific research: 20 years of community action by the Vancouver area network of drug users

Background: Over the past several decades, there have been numerous peer-reviewed articles written about people who use drugs (PWUDs) from the Downtown Eastside neighborhood of Vancouver, Canada. While individual researchers have engaged and acknowledged this population as participants and community partners in their work, there has been comparatively little attention given to the role of PWUDs and drug user organizations in directing, influencing, and shaping research agendas. Methods: In this community-driven research, we examine 20 years of peer-reviewed studies, university theses, books, and reports that have been directed, influenced, and shaped by members of the activist organization the Vancouver Area Network of Drug Users (VANDU). In this paper, we have summarized VANDU’s work based on different themes from each article. Results: After applying the inclusion criteria to over 400 articles, 59 items containing peer-reviewed studies, books, and reports were included and three themes of topics researched or discussed were identified. Theme 1: ‘health needs’ of marginalized groups was found in 39% of articles, Theme 2: ‘evaluation of projects’ related to harm reduction in 19%, and Theme 3: ‘activism’ related work in 42%. Ninety-four percent of co-authors were from British Columbia and 44% of research was qualitative. Works that have been co-authored by VANDU’s members or acknowledged their participations created 628 citations. Moreover, their work has been accessed more than 149,600 times. Conclusions: Peer-based, democratic harm reduction organizations are important partners in facilitating groundbreaking health and social research, and through research can advocate for the improved health and wellbeing of PWUDs and other marginalized groups in their community. This article also recommends that PWUDs should be more respectfully engaged and given appropriate credit for their contributions.Medicine, Faculty ofOther UBCNon UBCPopulation and Public Health (SPPH), School ofReviewedFacult

The challenges, opportunities and strategies of engaging young people who use drugs in harm reduction: insights from young people with lived and living experience.

The meaningful inclusion of young people who use or have used drugs is a fundamental aspect of harm reduction, including in program design, research, service provision, and advocacy efforts. However, there are very few examples of meaningful and equitable engagement of young people who use drugs in harm reduction, globally. Youth continue to be excluded from harm reduction programming and policymaking; when they are included, they often face tokenistic efforts that lack clear expectations, equitable work conditions, and are rarely afforded agency and autonomy over decision-making. In this commentary, we identify and discuss issues in youth engagement, and offer recommendations for the future of harm reduction

Participant, peer and PEEP: considerations and strategies for involving people who have used illicit substances as assistants and advisors in research

Background: The Peer Engagement and Evaluation Project (PEEP) aimed to engage, inspire, and learn from peer leaders who represented voices of people who use or have used illicit substances, through active membership on the ‘Peeps’ research team. Given the lack of critical reflection in the literature about the process of engaging people who have used illicit substances in participatory and community-based research processes, we provide a detailed description of how one project, PEEP, engaged peers in a province-wide research project. Methods: By applying the Peer Engagement Process Evaluation Framework, we critically analyze the intentions, strategies employed, and outcomes of the process utilized in the PEEP project and discuss the implications for capacity building and empowerment among the peer researchers. This process included: the formation of the PEEP team; capacity building; peer-facilitated data collection; collaborative data analysis; and, strengths-based approach to outputs. Results: Several lessons were learned from applying the Peer Engagement Process Evaluation Framework to the PEEP process. These lessons fall into themes of: recruiting and hiring; fair compensation; role and project expectations; communication; connection and collaboration; mentorship; and peer-facilitated research. Conclusion: This project offers a unique approach to engaging people who use illicit substances and demonstrates how participation is an important endeavor that improves the relevance, capacity, and quality of research. Lessons learned in this project can be applied to future community-based research with people who use illicit substances or other marginalized groups and/or participatory settings.Medicine, Faculty ofOther UBCNon UBCPopulation and Public Health (SPPH), School ofReviewedFacult

Patient perspectives of methadone formulation change in British Columbia, Canada: outcomes of a provincial survey

Background: In British Columbia, Canada, methadone maintenance treatment formulation transitioned from the oral liquid compound Tang™-flavoured methadone to the ten-times more concentrated cherry-flavoured Methadose™ in February 2014. We quantitatively describe perceptions and reported consequences among a sample of patients on methadone maintenance treatment following this transition. Methods A province-wide survey was used. Bivariable analyses utilized independent samples t-tests, Phi associations, and Chi-square tests. Multivariable logistic regression analyses evaluated factors related to dependent variables – namely, increases in dose, pain, dope sickness, and the need to supplement with additional opioids. Results Four hundred five methadone maintenance treatment patients from fifty harm reduction sites across British Columbia reported transitioning to Methadose™ in February 2014. The majority (n = 258; 73.1 %) heard about the formulation change from their methadone provider or pharmacist. Adjusted models show worse taste was positively associated with reporting an increasing dose (OR = 2.46; CI:1.31–4.61), feeling more dope sick (OR = 3.39; CI:1.88–6.12), and worsening pain (OR = 4.65; CI:2.45–8.80). Feeling more dope sick was positively associated with dose increase (OR = 2.24; CI:1.37–3.66), and supplementing with opioids (OR = 8.81; CI:5.16–15.05). Conclusions Methadone maintenance treatment policy changes in British Columbia affect a structurally vulnerable population who may be less able to cope with transitions and loss of autonomy. There may be a psychosocial component contributing to the perception of Methadose™ tasting worse, and increased dope sickness, pain, and dose. Our study shows the pronounced negative impacts medication changes can have on patients without informed, coordinated efforts. We stress the need to engage all stakeholders allowing for communication about the reasons, risks and consequences of medication policy changes and provision of additional psychosocial support.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacult

Pain as a risk factor for substance use: a qualitative study of people who use drugs in British Columbia, Canada

Background: People who use drugs have a significantly higher prevalence of chronic non-cancer pain compared to the general population, yet little is known about how various policy, economic, physical, and social environments may serve as risk or protective factors in the context of concurrent pain and substance use. Therefore, this study sought to explore perspectives, risks, and harms associated with pain among people who use drugs. Methods: Thirteen focus group interviews were held across British Columbia, Canada, from July to September 2015. In total, 83 people who had lived experience with substance use participated in the study. Using an interpretive description approach, themes were conceptualized according to the Rhodes’ Risk Environment and patient-centered care frameworks. Results: Participants described how their experiences with inadequately managed pain in various policy, economic, physical, and social environments reinforced marginalization, such as restrictive policies, economic vulnerability, lack of access to socio-physical support systems, stigma from health professionals, and denial of pain medication leading to risky self-medication. Principles of patient-centered care were often not upheld, from a lack of recognition of patients as experts in understanding their unique pain needs and experiences, to an absence of shared power and decision-making, which often resulted in distrust of the patient-provider relationship. Conclusions: Various risk environments and non-patient-centered interactions may contribute to an array of health and social harms in the context of inadequately managed pain among people who use drugs.Medicine, Faculty ofOther UBCPopulation and Public Health (SPPH), School ofReviewedFacult

Peer engagement in harm reduction strategies and services : a critical case study and evaluation framework from British Columbia, Canada

Background Engaging people with drug use experience, or ‘peers,’ in decision-making helps to ensure harm reduction services reflect current need. There is little published on the implementation, evaluation, and effectiveness of meaningful peer engagement. This paper aims to describe and evaluate peer engagement in British Columbia from 2010–2014. Methods A process evaluation framework specific to peer engagement was developed and used to assess progress made, lessons learned, and future opportunities under four domains: supportive environment, equitable participation, capacity building and empowerment, and improved programming and policy. The evaluation was conducted by reviewing primary and secondary qualitative data including focus groups, formal documents, and meeting minutes. Results Peer engagement was an iterative process that increased and improved over time as a consequence of reflexive learning. Practical ways to develop trust, redress power imbalances, and improve relationships were crosscutting themes. Lack of support, coordination, and building on existing capacity were factors that could undermine peer engagement. Peers involved across the province reviewed and provided feedback on these results. Conclusion Recommendations from this evaluation can be applied to other peer engagement initiatives in decision-making settings to improve relationships between peers and professionals and to ensure programs and policies are relevant and equitable.Medicine, Faculty ofOther UBCNon UBCPopulation and Public Health (SPPH), School ofReviewedFacultyResearcherGraduat

Guideline development in harm reduction: considerations around the meaningful involvement of people who access services.

BACKGROUND: Harm reduction seeks to minimizes the negative effects of drug use while respecting the rights of people with lived and living experience of substance use (PWLLE). Guideline standards ("guidelines for guidelines") provide direction on developing healthcare guidelines. To identify essential considerations for guideline development within harm reduction, we examined whether guideline standards are consistent with a harm reduction approach in their recommendations on involving people who access services. METHODS: We searched the literature from 2011-2021 to identify guideline standards used in harm reduction and publications on involving PWLLE in developing harm reduction services. We used thematic analysis to compare their guidance on involving people who access services. Findings were validated with two organizations of PWLLE. RESULTS: Six guideline standards and 18 publications met inclusion criteria. We identified three themes related to involving people who access services: , and . Subthemes varied across the literature. We identified five essential considerations for guideline development in harm reduction: establishing a shared understanding of reasons for involving PWLLE; respecting their expertise; partnering with PWLLE to ensure appropriate engagement; incorporating perspectives of populations disproportionately affected by substance use; and securing resources. CONCLUSION: Guideline standards and the harm reduction literature approach the involvement of people who access services from different perspectives. Thoughtful integration of the two paradigms can improve guidelines while empowering PWLLE. Our findings can support the development of high-quality guidelines that align with the fundamental principles of harm reduction in their involvement of PWLLE

“It’s an emotional roller coaster… But sometimes it’s fucking awesome” : Meaning and Motivation of Work for Peers in Overdose Response Environments in British Columbia

The province of British Columbia (BC), Canada is amid dual public health emergencies in which the overdose epidemic declared in 2016 has been exacerbated by restrictions imposed by the Coronavirus Disease of 2019 (COVID-19) pandemic. Experiential workers, commonly known as ‘peers’ (workers with past or present drug use experience) are at the forefront of overdose response initiatives and are essential in creating safe spaces for people who use drugs (PWUD) in harm reduction. Working in overdose response environments can be stressful, with lasting emotional and mental health effects. There is limited knowledge about the personal meaning that experiential workers derive from their work, which serve as motivators for them to take on these often stressful roles.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacultyResearche