Program: Scholar

A causal inference framework for analyzing large administrative healthcare databases with a focus on multiple sclerosis

Provincial health authorities routinely collect patient information on a massive scale, but health researchers face the challenge of exploring cause-and-effect relationships using these non-randomized population-based data sources. Machine learning methods are increasingly used to analyze these large datasets, although they do not inherently take causal structures (i.e., how the variables affect each other) into consideration and may lead to less-than-optimal or even erroneous conclusions.

Health researchers urgently need new big-data analytic methods that are geared towards extracting causal explanations rather than merely increasing prediction accuracy. This project will develop innovative biostatistical methodologies that will better equip health researchers to infer causation from big-data sources.

As a motivating problem, with a bias reduction goal in mind, Dr. Karim will investigate potential benefits of disease-modifying drugs in multiple sclerosis patients 50 years of age or older. Ultimately, this methodological development will enable health researchers to convert information into actionable knowledge for other common, chronic conditions, leading to cost-effective medical decision making and improving the health of Canadians.

Population-based ‘big data’ research to improve women’s health

Dr. Hanley's research in women's reproductive health uses the large population-based datasets that already exist in British Columbia, and is driven by diverse training in population and public health, health services research, and economics.

Specifically, Hanley will study whether removing a woman's fallopian tubes at the time of other routine gynecologic surgeries is a safe, effective and cost-effective ovarian cancer prevention strategy. This will provide much needed and timely evidence on the effectiveness of removing the fallopian tubes as an ovarian cancer prevention strategy. Known as the British Columbia protocol, this practice has been adopted in many countries around the world.

Hanley will also examine the safety of using psychotropic medicines during pregnancy, specifically whether using antidepressants during pregnancy may increase a child's risk for autism spectrum disorder and social and emotional and motor development in early childhood. This will generate evidence that can be used to minimize or avoid adverse outcomes from maternal mental illness and use of prescription drugs to treat that illness in pregnancy.

This focus on women's reproductive health and the use of the large linkable population-based datasets in BC will generate evidence on improving population health, improving patient care, and reducing health system costs. This research has already, and will continue to, guide patient care in British Columbia.

Mental health trajectories of immigrant and refugee children: An ecological population-based approach

Canada’s immigrant and refugee population is growing rapidly, representing over 20% of the population. Despite the significance for Canadian society, little is known about mental health and risk factors among immigrant and refugee children and youth. Such knowledge is, however, critical to understand how we can support them in adapting to Canada, and enhance their well-being. This project aims to create actionable evidence that health professionals, educators, and decision-makers can use to implement initiatives that can support the mental health of immigrant and refugee children and youth.

This research will:

  1. Use statistical analyses of multiple databases, linked at a population-level across 10 school districts of BC, to examine how child, family, school, and community factors relate to immigrant and refugee children’s mental health outcomes, and how these children and youth are using health services in BC.
  2. Ask immigrant and refugee youth about their perspectives on factors related to their mental health and access/barriers to mental health services, via interview focus groups in school and mental health clinic settings.

This is the first study in BC to combine province-wide data with children’s own perspectives to identify which factors may need to be addressed and what future prevention and intervention efforts are needed to support long-term health outcomes for immigrant/refugee children and youth in Canada.

End of Award Update – June 2023

Most significant outputs

This project allowed us to study and identify population-level diagnostic prevalence of mental health disorders across immigrant, refugee, and non-immigrant children and youth in British Columbia (BC). In this research, we found notable differences in the diagnostic prevalence rates of conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and mood/anxiety disorders across immigrant, refugee, and non-immigrant children and youth, as well as across factors such as sex, age, and immigrant/refugee generation status.

This project also allowed us to delve more deeply into the factors that might impact the emotional health of refugee children. This research identified that specific factors associated with refugee children’s perceptions of their social context (e.g. a supportive school climate, support from adults at school) were associated with better emotional health.

 

Impact

To our knowledge, our research is the first to provide population-level mental disorder prevalence estimates that compare immigrant, refugee, and non-immigrant groups in BC. This provides important information to our understanding of the mental health status of immigrant and refugee children and youth in BC.

 

Potential Influence

We hope that this work will be the impetus for additional research examining the unique mental health patterns and needs of diverse child and youth sub-populations that tend to be underrepresented in mental health research. Understanding the unique needs of Canada’s diverse sub-populations is particularly important for health service planning and informing health policies.

 

Next Steps

With the support of a Tier 2 Canada Research Chair and funding from the Canadian Institutes of Health Research and Social Sciences and Humanities Research Council of Canada, we are continuing our work to deepen our understanding of the developmental trajectories and unique mental health needs of diverse children and youth in BC.

Neuromodulation research program for youth addiction and mental health

Each year, approximately 1 in 5 Canadians experiences a mental health or addiction problem. Young people aged 15 to 24 are more likely to experience mental illness and substance use than other age groups.

Depression is one of the most common mental illness, but current treatments are either ineffective or lead to side effects in up to 50% of youth. In youth, medications are often borrowed from adult population not accounting for age-related brain differences. New solutions are needed to address major gaps in treatment of youth mental health.

Dr. Farzan is collaborating with physicians, neuroscientists, engineers, and health authorities to develop and apply more precise and innovative methodologies to study the brain and address this gap. She is combining non-invasive brain stimulation and brain monitoring technologies to study what may underlie depression in young age, and how each treatment affects the brain. She is also developing non-invasive brain stimulation technologies for youth that do not respond to medications or behavioral therapy. This research has tremendous potentials for leading to introduction of a new therapy for youth who are failing currently available treatments.

Phosphoinositide kinases: Molecular determinants for their regulation and role in human disease

Lipids are the primary constituent of all cellular membranes, however, they also can play key roles as signaling molecules that controls how a cell responds to its environment.  Almost every aspect of a cell's decision to live and die is impacted by the role of lipid signals called phosphoinositides. These signals are generated in the correct location and at the appropriate time by proteins in our body called phosphoinositide kinases (PI kinases). Misregulation of PI kinases is a key driver of disease, including cancer and immunodeficiencies.

Intriguingly host PI kinases are frequently hijacked by pathogenic viruses to mediate viral replication, and targeted inhibition of parasite PI kinases is a promising therapeutic strategy for treatment of malaria and cryptosporidiosis (a diarrheal disease caused by microscopic parasites). Therefore, understanding the molecular basis for how PI kinases are regulated is of extreme biomedical importance.

Dr. Burke's research is focused on understanding the molecular basis for regulation of PI kinases, and how they are involved in human disease. He and his team have revealed fundamental insight into how these enzymes are involved in cancer and immunodeficiences, and how viruses manipulate them to mediate infection. Overall this work is important in understanding how lipid signals mediate disease, and will be critical in the design of inhibitors as novel therapeutics.

Improving youth mental health and substance use outcomes through primary-care based health services

Mental health and substance use (MHSU) disorders affect 1 in 4 Canadian youth. Of all age groups, young Canadians (ages 15 to 24) have the poorest access to health services. In response, British Columbia (BC) established a primary health initiative called 'Foundry' to promote and support early treatment for young people with MHSU disorders. Foundry is comprised of seven centres that provide integrated, coordinated health services for young people. The aim of my five-year research program is to improve health outcomes for youth accessing Foundry services through enhanced patient-centred assessment and evidence-based care tailored to the specific needs of young people experiencing MHSU challenges.

The key elements of this research program include:

  1. Enhancing the role of youth in MHSU research.
  2. Measuring and understanding the health needs of young people with MHSU disorders.
  3. Developing tailored and accessible treatments for youth with MHSU, including employment support.

Over the next five years, Dr. Barbic will work collaboratively with Foundry and other community organizations across BC to identify the health priorities of youth with MHSU disorders, and use new methods to measure these priorities and demonstrate how patient-centred assessment can drive meaningful care. By engaging youth, families, clinicians and trainees, this research program will address a national priority to improve the health outcomes of young people with MHSU disorders. 

Precise prescription of rTMS for treatment resistant depression

Dr. Vila-Rodriguez's research will work towards improving diagnostic accuracy and treatment outcomes in persons suffering treatment-resistant depression (TRD). By incorporating neurophysiological-based biomarkers (NPBs) into clinical practice, treatment response can be more easily predicted, preventing relapse in patients with major depressive disorder. This program of research focuses on the use of repetitive transcranial magnetic stimulation (rTMS), a non-invasive neurostimulation therapy recommended by the Canadian Network for Mood and Anxiety Treatments (CANMAT) as a first-line treatment option for TRD.

This research encompasses the Canadian rTMS Treatment and Biomarker Network in Depression (CARTBIND) trial, an ongoing randomized clinical trial that aims to identify relevant NPBs and uses rTMS to treat TRD. Participants in this trial undergo resting-state electroencephalographic and resting-state functional magnetic resonance imaging before and after rTMS treatment to ascertain which neurophysiological features are good predictors of treatment response. Based on this data Dr. Vila-Rodriguez will develop and test a treatment response classifier and relapse prediction classifier.

The aim of this research is to transform how clinicians prescribe rTMS and how they monitor the treatment course and maintenance by incorporating reliable and robust biomarkers. This approach will optimize treatment efficiency by increasing the response rates for TRD and reducing treatment failure, thereby improving the health of British Columbians who struggle with depression and decreasing costs to the health care system.

Dr. Vila-Rodriguez's knowledge translation model involves the regular use of both the lab website as well as the Twitter account to engage his research audience in research activities to keep them up-to-date on new findings, as well as to facilitate self-learning via educational materials.

Genetic etiology of progressive multiple sclerosis

Multiple sclerosis (MS) is the most common cause of neurological disability in young adults, other than trauma, with over two million people affected worldwide. Approximately 100,000 Canadians have MS, a rate that is nine times higher than the global average. MS symptoms vary widely and may affect vision, hearing, cognition, balance, and movement; negatively affecting many aspects of quality of life. To date, there is no cure or prevention for MS. Although treatments to effectively manage the clinical symptoms of MS are available, they come with several serious and even life-threatening adverse effects; and over time, MS enters a progressive phase which no known therapies can prevent or treat. MS was originally considered an autoimmune disease triggered by exposure to environmental factors, but family studies (twins, adoptees, half siblings) have clearly demonstrated an important genetic component to the disease.

The goal of this research program is to define the genetic components contributing to the onset of MS to provide new tools for scientific investigation and the development of novel and more effective treatments. To this end, Dr. Vilarino-Guell will apply new gene sequencing technologies to over 100 families with several blood relatives presenting with MS, as well as thousands of unrelated individuals diagnosed with MS. Within the last year he has identified disease-causing genetic changes for some of these families, as well as biologically-relevant genetic changes which impact disease progression and the severity of clinical symptoms. These genes and mutations have highlighted specific biological pathways implicated in the onset of progressive MS.

This research will further characterize the genes involved in these cellular processes to better understand the biological mechanisms of progressive disease. The results of Dr. Vilarino-Guell's research will provide the knowledge and tools for the therapeutic advances in the prevention and treatment of MS, tackling its highly debilitating progressive phase which is currently untreatable.

The role of the norepinephrine system in emotionally-biased attention and learning

Individuals vary widely in the aspects of the world they perceive and remember: some filter their environments through rose coloured glasses to perceive sources of pleasure, while others are attuned to signs of threat. Such affective biases in attention influence memory and characterize mood disorders and pathological responses to trauma as well as addictive behaviours. Yet much remains to be learned about neural mechanisms underlying such biases, and the factors that influence their development and potential for change.

Dr. Todd's research will investigate the influence of genetic variation and life experience on emotional biases in learning, attention and memory, and how they can be harnessed to treat affective disorders and addiction. This research will have a direct impact on our understanding of basic neural mechanisms underlying such affective biases, and increase our understanding of how genetic variation and life experience shape these mechanisms to produce behaviours linked to mood disorders and addiction, with important implications for assessing vulnerability and optimizing treatment.

Dr. Todd's five-year research program will work towards an understanding of the role of common genetic variations that influence neurochemical activity in the brain, and the development of behaviour patterns that are linked to mood disorders. Extending her previous work on the influence of genetics and trauma on emotional biases in attention, she will focus on understanding neural mechanisms underlying such biases; investigate whether such biases arise out of individual differences in patterns of emotional learning; and examine the influence of a common genetic variation that influences the availability of norepinephrine in emotional learning. The results of this research will aid understanding of the currently understudied role of norepinephrine in emotional learning patterns linked to mood disorders and addiction.

Responding to the dual epidemics of hepatitis C and addiction in British Columbia

In British Columbia (BC), it is estimated that 78,000 people are living with hepatitis C virus (HCV), most of whom do not even know they have the disease. If left untreated, HCV can cause serious harm, including liver cancer and death. People who inject drugs (PWID) are at elevated risk of HCV infection given their exposure to various individual and environmental circumstances, such as their ongoing addiction and barriers to accessing health care. A growing body of research suggests that harm reduction and addiction treatment programs may present important opportunities to engage PWID in the HCV treatment and care. Efforts are now underway in BC to dramatically expand access to low-threshold addiction treatment that extends beyond traditional methods. Research in this area is particularly timely, as these new policies offer an opportunity to evaluate the impacts of the expansion and optimization of addiction treatment on HCV-related outcomes among PWID.

Dr. Ti's research is an extension of past work that focused on the relationships between infectious diseases, addiction, and the delivery of harm reduction and health services. Utilizing her expertise in this area, Ti will evaluate novel interventions to reduce the health burden caused by HCV and addiction by:

  • Characterizing HCV re-infection rates among PWID and examining harm reduction-based and addiction treatment interventions that may protect against reinfection.
  • Evaluating evolving addiction treatment guidelines and their impact on HCV incidence among PWID.
  • Evaluating the impact of innovative HCV and addiction treatment interventions on treatment uptake and completion.

This research is designed to provide evidence for health system leaders and policy makers to develop policies that are in line with evolving trends in HCV and addiction, and to support health system improvement.