Evaluation of innovative risk mitigation services in the context of dual crises of COVID-19 and overdose among people who use opioids in Vancouver, BC

Through funding from the Canadian Institute of Health Research (CIHR) and MSFHR, Principal Investigators Dr. Kanna Hayashi, Research Scientist at the BC Centre on Substance Use (BCCSU) and St. Paul’s Hospital Chair in Substance Use Research and Assistant professor in the Faculty of Health Science at Simon Fraser University (SFU) along with Dr. Kora DeBeck, Research Scientist at the BCCSU and Associate Professor in the SFU School of Public Policy aim to conduct preliminary evaluation of two novel measures introduced by the BC government in March 2020 to address the dual crisis of overdose and COVID-19.

Specifically, these measures include expanding the opioid agonist treatment (OAT) prescription guidelines and pandemic prescribing of pharmaceuticals (e.g. opioids) to people who use illicit drugs. By providing pharmaceutical alternatives to the toxic illicit drug supply, the interventions are intended to reduce physical encounters involved in obtaining illicit drugs and the use of toxic street drugs, thereby supporting both overdose and COVID-19 prevention efforts. To date, however, the impacts of these interventions have not been evaluated.

The proposed BC-based research aims to fill critical knowledge gaps by examining the reach and preliminary impacts of pandemic prescribing and expanded OAT prescription services among people who use opioids in urban Vancouver. Through this work, the research team, which consists of highly productive investigators and knowledge users with direct clinical and policy expertise, seeks to inform efforts to improve the delivery and effectiveness of the interventions.

Funding Competition: CIHR Operating Grant: COVID-19 Mental Health & Substance Use Service Needs and Delivery Funding Opportunity

Funders: CIHR; MSFHR

Tracking the Prevalence and Incidence of Modifiable Suicide Risk Factors During the COVID-19 Pandemic to Inform Targeted Suicide Prevention in British Columbia

Problem: Half of Canadians report worsened mental health since the COVID-19 pandemic began disrupting our lives this Spring. These impacts, combined with rising prevalence of known suicide risk factors such as unemployment and financial hardship, social isolation, alcohol and substance use, relationship strain and domestic violence, have raised concerns that of rising suicide risk in the Canadian population. Canada loses 3,800 to 4,500 lives to suicide each year. Suicide death and bereavement confer long-term psychological and social risk to families and communities. A small increase in suicide rate can thus result not only in excess loss of life, above and beyond the direct impacts of the pandemic, but also confer long-term vulnerability in our communities.

Research: In collaboration with an international team of researchers led by investigators Shanaya Rathod and Peter Phiri in the UK, our Canadian team aims to characterize the specific mental health and related cognitive impacts of the COVID-19 pandemic to inform evidence-based policy that can mitigate secondary mental health and suicide risk. We will conduct three pan-Canadian general population surveys, in September 2020, December 2020, and March 2021. For each survey, we will recruit at least 5,000 community adults, balanced by sex, age, and geographic region. Surveys will focus on Canadians' emotional, physical, and cognitive wellbeing across distinct phases of the pandemic. In addition, we will work with mental health service leaders, providers and users to co-create supplemental surveys to assess the mental health experiences and needs of three potentially vulnerable groups: frontline health workers, Indigenous peoples, and people living in rural or remote areas. Our results can inform mental health strategies by identifying where, with whom, and what kind of intervention is needed to effectively reduce suicide risk in the population. Support from MSFHR and the BC Ministry of Health will enable us to over-sample British Columbians so that we can understand mental health needs within this province and identify sectors or populations with mental health needs.

Research Team: Our interdisciplinary research team, led by Co-PIs Brianna Turner, Theone Paterson, and Chris Lalonde, includes psychology, social work, and sociology researchers, as well as community knowledge users representing the United Way of the Lower Mainland, the Ontario Association of Social Workers, and the Canadian Mental Health Association.

Website: https://onlineacademiccommunity.uvic.ca/covidmentalhealth

Funding Competition: CIHR Operating Grant: COVID-19 Mental Health & Substance Use Service Needs and Delivery Funding Opportunity

Funders: CIHR; MSFHR

Keywords: Suicide Prevention, Mental Health, Sleep, Depression, Substance Use, Social Connectedness, Public Health, Survey

Addressing the dual public health crises of COVID-19 and overdose

A team led by Dr. Amanda Slaunwhite, Senior Scientist with the BC Centre for Disease Control and an adjunct professor in the School of Population and Public Health, were awarded $75,000 from the Michael Smith Foundation for Health Research and $777,439 from CIHR as part of the Novel Coronavirus (COVID-19) Rapid Research Funding Opportunity. The researchers will assess the impact of the new risk-mitigation guidance that permits prescribing of pharmaceutical alternatives to the toxic drug supply. Researchers will determine the effects of the pandemic and risk mitigation measures on COVID-19 infection, continuity of care for treatment of substance use disorders and non-fatal and fatal overdose in BC. The researchers will also identify barriers and facilitators to implementation from the perspectives of people who use substances, prescribers, harm reduction workers, and other providers and community members.

The team is led by principal investigators at UBC, the Canadian Institute for Substance Use Research (CISUR) at the University of Victoria (Dr. Bernie Pauly and Dr. Karen Urbanoski) and Simon Fraser University (Dr. Bohdan Nosyk and Dr. Natt Hongdilokkul). The team includes co-investigators and collaborators from the First Nations Health Authority, Ministry of Mental Health and Addictions, BC Centre on Substance Use, the BCCDC-based Compassion Inclusion and Engagement (CIE) (PEEP) peer network, Provincial Health Services Authority, BC-Yukon Association of Drug War Survivors and Public Health Agency of Canada.

Funding Competition: CIHR Operating Grant: COVID-19 Rapid Research Funding Opportunity – Social Policy and Public Health Responses

Funders: CIHR; MSFHR

Extracellular vesicle associated glycans as a novel platform for breast cancer detection

Breast cancer is the most common cancer amongst women in Canada. Breast cancer cells shed tiny pieces of themselves into the blood stream called extracellular vesicles. These tiny pieces, or cell fragments, are different from those of a healthy breast cell and we think they could be used to detect a breast cancer at its earliest stage. Importantly, we can isolate and study these fragments from the blood of healthy females and breast cancer patients. We think that by looking at the sugars and proteins they contain we will find markers that could help in the detection of breast cancer. We are also going to look at tumor cell fragments from patients whose cancer came back years after treatment, a process known as metastasis, and find unique markers that could predict this outcome. By identifying breast cancer early and figuring out whose at risk for a having their cancer come back we can improve how women are treated and reduce the chances of the cancer coming back.

MSFHR is providing match funding to the glycomics-based early cancer detection project which is funded by the Canadian Glycomics Network through a GlycoNet Collaborative Team Grant. This Pan-Canadian project involves research teams in British Columbia and Alberta. Dr. Williams, lead PI, is an assistant professor at UBC’s Faculty of Pharmaceutical Sciences and her team includes clinical pathologist Dr. Peter Watson (BC Cancer) and Professor of Chemistry Dr. Lara Mahal (University of Alberta).

End of award update: November 2021

Following the end of her award term, Dr. Williams has provided the following brief update on this project’s progress.

Most exciting outputs:
Our project successfully isolated small cell fragments, termed extracellular vesicles, from blood plasma of hundreds of breast cancer patients and healthy females. From this, we were able to look at the sugars and proteins on these fragments to identify ones unique to breast cancer patients. This has allowed us to find a couple unique markers that we think can be used to identify breast cancer at its earliest stage of development.

Impact so far:
Detecting cancer at the earliest stage will support the best outcome for patients. This is particularly relevant in breast cancer as it is well established that a disease diagnosis at an early stage, Stage I, is associated with the highest rates of patient survival. Our project has identified novel sugar and protein based biomarkers with utility in identifying breast cancer. Validation of newly identified biomarkers could lead to the development of a blood-based test for breast cancer screening.

Potential future influence:
Our project aims to reduce the mortality associated with a breast cancer diagnosis. To do this we are aiming to develop a non-invasive test that will support the detection of breast cancer at its earliest stage.

Next steps:
We plan to validate our newly discovered breast cancer biomarkers and work towards translating our results into a product that could be used as a simple point-of-care test by a family doctor.

Please visit GlycoNet to learn more about this project.

Ventilation Heterogeneity in Asthma, COPD and Asthma-COPD Overlap: Oscillometry and Pulmonary MRI

Airways disease is a hallmark finding in both asthma and chronic obstructive pulmonary disease (COPD). Although tobacco cigarette smoking is the largest known cause of COPD, recent studies have revealed that 10% of patients with life-long asthma may develop COPD later in life without ever smoking. The mechanisms underlying asthma transition to COPD are unknown. To better understand this transition, this proposal will use 129Xe magnetic resonance imaging (MRI), computed tomography (CT) imaging and oscillometry to measure airway abnormalities in patients with asthma, COPD, and asthma-COPD overlap. These measurements will provide a better understanding of airway abnormalities that contribute to development of COPD in these patients with asthma. COPD is the most common cause of hospital admission in Canada and treatment costs in BC alone are estimated to be over $600M/year. The results generated from this proposal may identify new ways to treat COPD or halt its development in patient with asthma, contributing to reduced hospital admissions and costs related to COPD.

Vitamin C-induced epigenomic remodeling as a preventive therapy for leukemic transformation

Despite the overall improved diagnostics, standard of care and therapeutic options, most acute myeloid leukemia (AML) patients suffer from severe therapy-related side effects and still only 28% of them reach 5-year overall survival. The hypothesis that drives my project is that mutations which affect DNA-modifying enzymes disrupt a methylation-based control mechanism that regulates gene expression in a way that halts the normal cellular differentiation process. The discovery that vitamin C acts as an enzymatic co-factor that is able to revert this methylation defect in affected cells, provides a unique opportunity to transfer this knowledge to the development of novel, less toxic treatment strategies for patients that harbour these mutations. Within the scope of this project, I plan to explore whether and to which extent I can restore the normal DNA methylation signature in patient-derived leukemic cells in mice, either through vitamin C treatment alone or in addition to Health-Canada approved AML drugs. Further, I will explore the potential of vitamin C treatment to delay or prevent the transformation of not yet leukemic cellular states towards myeloid malignancy.

Resisting Vascular Cognitive Impairment: The Effects of Resistance Training on Myelin and Blood-based Biomarkers of Neuroplasticity in Older Adults

We are studying if strength training exercises can reduce myelin loss and preserve cognitive abilities in adults with cognitive impairment due to vascular risk factors (e.g., high blood pressure), also known as vascular cognitive impairment (VCI).

Worldwide, VCI is the second most common cause of dementia and it is associated with myelin loss. Myelin is a component of neurons critical for transmission of brain signals. Thus, myelin is important for the maintenance of cognitive (i.e., thinking) abilities. Animal studies suggest myelin loss may be minimized with physical exercise. The objective is to determine whether strength training (e.g., lifting weights) is an effective strategy for slowing down myelin loss in persons with VCI. 

We will conduct a 12-month study with 88 adults with VCI; half will receive strength training and half will receive balance and stretching exercises. At the end of study, the two groups will be compared on myelin content and cognitive function. Reducing myelin loss could preserve cognitive abilities in adults with VCI and reduce their risk of dementia. Our proposal is also timely as the prevalence and burden of VCI will only increase with the world’s aging population.

Promoting mental health in immigrant, refugee, and non-immigrant children: A British Columbia intergenerational population cohort study

Mental health problems are estimated to be the most common disabling condition among adolescents worldwide, with children growing up in socially disadvantaged homes having up to three times the risk of mental health problems compared to children without such disadvantage. Studies show a high degree of intergenerational stability in these patterns, with social stressors putting particular subgroups of children at higher risk from the earliest stages of development. Immigrant and refugee children make up a significant proportion of the BC child population, and have a unique set of circumstances that may increase or decrease their risk of mental health problems as they reach adolescence. In BC, an established system of child development monitoring paired with new data linkages to provincial health, immigration, and Statistics Canada records create a globally unique opportunity to investigate continuities from maternal mental health problems to childhood emotional symptoms and adolescent mental health problems, for immigrant, refugee, and non-immigrant children. The purpose is to identify opportunities to break these continuities, informing the timing and design of preventative interventions to promote population mental health.

Development of Novel Alpha-amanitin Analogs for Targeted Cancer Chemotherapy

New toxins for incorporation into treatments known as antibody-drug conjugates are urgently needed to ensure therapeutic action. These antibody-drug conjugates consist of an antibody, designed to target a specific group of cells, attached to an active drug that elicits a desired cell response. While most emergent payloads for clinical application target tubulin, making them redundant, the death cap mushroom contains a toxic peptide called alpha-amanitin with unique biological activity. Amanitin presents its toxicity by preventing the conversion of DNA to RNA, a process required for protein synthesis. This inhibition ultimately leads to cell death.  Amanitin’s high toxicity provides potential for a low dose cancer therapeutic if general toxicity to non-cancerous cells can be avoided. I seek to investigate the feasibility to harness amanitin’s bioactivity while delivering the toxin specifically to cancer cells by attaching a targeting agent. In order to facilitate these investigations, I will develop a scalable method to generate substantial amounts of the toxin. By utilizing this targeted approach, we anticipate a cancer cell-specific delivery of the toxin, which in turn would attenuate the off-target effects and general toxicity.

Modulating microRNA-193a expression levels as a treatment for acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) has a dismal prognosis in Canada with only every 5th patient surviving 5 years. To find novel treatment options, we explore the therapeutic potential of the tumor suppressor microRNA (miR)-193a in AML patients together with InteRNA, a company that developed a novel drug based on the liposomal encapsulation of miR-193a (1B3), which showed very promising preclinical results in solid tumors and provided the rational for a phase I trial starting in spring 2020. We and others have previously shown that miRNAs are small RNAs that impact leukemia cells and are an emerging class of drugs. Recent data from our group showed a strong leukemia inhibition via miR-193a in animal AML models, highlighting the tumor suppressive effect of this miRNA. In addition, we are studying the regulation of miR-193a in AML cells to develop strategies to reinstate miR-193a expression and thus enhance its tumor suppressor function. This innovative study pioneers a novel class of RNA-based drugs in the treatment of AML and the groundwork for future clinical trials.