Pancreatic cancer kills almost 5,000 Canadians each year and if progress is not made to improve outcomes, the annual number of deaths will double by 2030. In 80% of patients, the cancer has spread at the time of diagnosis, and is not operable. Most of these patients die within one year due to the lack of effective therapies and the fact that clinicians have no clear guidance on which existing treatment option would work best for individual patients.
Precision medicine in cancer has gained a lot of attention in the last decade, as it may provide the best approach to treating tumours on an individual basis. Cancer treatment does not benefit from the one-size-fits-all approach because individual tumours, even if affecting the same organ, are biologically different, which can impact their response to treatment. Tumour subtyping, a method by which scientists identify the unique characteristics of individual tumours, is critical for precision medicine enabling personalized treatment based on the tumour's specific biological traits. Advances in the understanding of cancer subtypes have revolutionized treatment in multiple cancers, but we have yet to uncover pancreatic cancer subtypes that can help with treatment decisions.
Our goal is to define clinically meaningful pancreatic tumour subtypes, and study their impact on tumour aggressiveness and response to treatment. These findings will be rapidly translated to the clinic to have immediate impact on treatment selection for patients. We will perform detailed genetic and molecular analysis of patient tumour samples to investigate the distinct molecular characteristics. The patients will be enrolled in a clinical trial at the BC Cancer Agency and will be provided with detailed and cutting edge analyses of their tumours to help the clinical team guide further therapy decisions.
Currently, over 90% of diagnosed pancreatic cancer patients are not expected to survive five years. Our program has the potential to dramatically change the trajectory of pancreatic cancer and improve outcomes for thousands of Canadians diagnosed with the disease.
Throughout the history of medicine, patients who had a disease that was poorly understood were advised to rest. As scientists and doctors learned more, early mobilization and active therapies (e.g., exercise) gradually replaced rest as the conventional treatment for a variety of medical conditions, such as chronic fatigue, whiplash, stroke, low back pain, and cardiac arrest. We have now reached this same juncture for concussion care. The proposed project aims to figure out how to support doctors in implementing new science-informed return to activity guidelines for concussion.
By way of background, concussions (also known as mild traumatic brain injuries) are very common, affecting more than 20,000 people each year in British Columbia's lower mainland alone. Concussions have been historically treated with rest. An explosion of concussion research over the past decade has led to several important insights. One such insight is that resting for more than a few days does not speed up recovery, and in fact, may cause harm (for example, lead to social isolation and depression). There is also emerging evidence that exercise is an effective treatment. Guidelines for clinical care prepared by Canadian and international concussion experts now emphasize that patients should gradually return to activity (e.g., school, work, recreation) soon after injury, as tolerated. Nevertheless, rest remains the most common treatment prescribed by doctors. It is promoted in pamphlets and websites designed to educate patients about their injury.
The goal of the proposed research is to bridge the gap between concussion science and clinical care, and study how effective this knowledge translation effort is. We focus on family doctors because they are best positioned to counsel patients about returning to activity after concussion. We have assembled a package of knowledge translation strategies based on behaviour change theory, prior research on how to best implement new clinical care guidelines, and input from the kind of doctors and patients who could most benefit from this knowledge. The study plan involves learning about doctors' behaviour through an online survey tool each time they see a patient with a concussion, and measuring patient outcomes through telephone-based assessments. We will measure changes in how doctors manage concussions and whether those changes result in corresponding improvements in how quickly patients recover from a concussion.
Many Canadians live with debilitating chronic gut disorders such as Crohn's or ulcerative colitis (also known as inflammatory bowel disease, or IBD), Clostridium difficile infection (CDI), or both. These disorders lead to increased morbidity and reduce quality of life and productivity for patients and their families. One in every 150 Canadians has IBD, which is the highest rate worldwide. CDI is the number one cause of health care-associated infection (HAI) in Canada, and associated costs are approximately $300 million per year. An added concern is the recent sharp increase in community-associated CDI rates in previously healthy individuals. Recurrence of CDI following treatment with antibiotics is approximately 30%, increasing to 60% after two or more recurrences.
The key reason for IBD and CDI is thought to be a major imbalance between good and harmful bacteria in the gut (also known as dysbiosis). Current treatments for these conditions are ineffective and costly, and do not establish beneficial bacteria (or microbiota) in the gut. Fecal transplantation, also known as fecal microbiota transplantation (FMT), is a promising new treatment that uses stool from a healthy screened donor to restore the healthy microbiota in the colon. However, FMT remains unavailable in most health care facilities in Canada despite high demand. Dr. Lee regularly receives phone calls and e-mails from patients with chronic gut conditions requesting FMT. FMT is not yet licensed for routine clinical use and out of desperation, some patients have explored the option of performing FMT at home using unscreened donor stools. One of the major challenges of establishing and sustaining an FMT program is the lack of suitable donors and the laboratory support to manufacture FMT. In order to improve availability and reduce cost, this program will use Lyophilized (freeze-dried) FMT, L-FMT. Dr. Lee has used L-FMT to 60 patients with CDI and its result is similar to fresh/frozen FMT.
The BCaLM (British Columbia Associated Lyophilized Microbiota Program) aims to: 1) establish the safety of L-FMT through long-term follow-up of recipients; and 2) establish an effective and safe program to deliver L-FMT across Canada. A multi-site study will evaluate the efficacy of L-FMT, and the results will be used to direct further research and establish capacity for L-FMT. The findings can offer a readily available, cost-effective, and improved treatment option for people with chronic gut disorders.
Pediatric obsessive-compulsive disorder (OCD) is a neuropsychiatric illness that has a 1-4 percent prevalence rate in children and youth. OCD is characterized by intrusive thoughts and repetitive behaviours, and although treatments, such as cognitive behavioural therapy (CBT), are available, better treatment selection could improve response rates.
To advance our understanding of the dysfunctional brain mechanisms underlying OCD, and eventually find predictive biomarkers of treatment response, functional magnetic resonance imaging (fMRI) has been used to find the neural correlates of OCD, particularly during symptom provocation tasks (i.e. tasks that allow researchers to probe the brain areas involved in emotional processing by exposing OCD patients to OCD-related stimuli). This research has given us neural correlates of OCD, but fMRI is expensive to implement in clinics.
The goal of this proposal is to use electroencephalography (EEG) to study OCD symptom provocation because it is less costly than fMRI and easily implemented in clinics. EEG also provides an innovative way to investigate OCD, as it provides a fine-grained temporal measure of brain activity, whereas fMRI provides a fine-grained spatial measure of brain activity. Thus, EEG could provide a new set of temporal psychophysiological correlates of OCD that would be easily and inexpensively collected in clinics, and that could predict CBT outcome. In the proposed study, clinically diagnosed pediatric OCD patients (12-18 years old), siblings unaffected by OCD (12-18 years), and matched healthy controls (HCs) will complete an OCD symptom provocation task that elicits emotional responses while EEG is recorded. Event-related potentials (ERPs) will then be derived from the EEG data and will be used to characterize the OCD group in comparison to the sibling and HC group, and to use as potential predictors of CBT response.
The proposed study is novel because few EEG studies of OCD symptom provocation exist, and no emotional-related ERP studies have been conducted in children, although pediatric studies are essential to our understanding of early brain differences.
Our findings will be presented to clinicians and researchers at annual conferences and published in leading peer-reviewed journals. Lay-friendly articles will also be written and submitted to the Canadian OCD Network’s and the International OCD Foundation’s newsletters.
Older men in assisted living spend up to 90 percent of their time in sedentary behavior. This lack of physical activity makes them more vulnerable to mobility-disability. Currently, 40 percent of Canadian men over the age of 75 already present some degree of mobility-disability. Mobility limitations lead to frailty, falls, and placement into higher levels of care. To promote mobility and physical activity in older men living in assisted living facilities, a better understanding of how they move is needed. This in turn helps assisted living facilities better customize programs that enhance their participation, and thus, improve their mobility.
To address the gaps, I will develop and evaluate strategies that promote mobility and physical activity (in older men who live in assisted living). More specifically, I will address the following two objectives:
- Examine how real-life measures from wearable sensors of the quality of movement (e.g. time required for transferring, gait speed) and quantity of movement (e.g. activity levels) associate with frailty and risk for falls in older men. I will use wearable sensors to measure mobility patterns during standard clinical tests and as residents go about their daily activities (e.g. walking, transferring, standing, seated, and lying).
- Examine how mobility and activity levels are influenced by a customized physical activity program and real-time feedback monitored by wearable sensors. I will conduct a 12-week randomized control trial of a customized physical activity intervention for older men in assisted living. Participants will be randomly assigned to either the program currently offered by a facility (control group) or to a physical activity program that is custom-designed based on the results under objective 1 (intervention group).
This project will be conducted in partnership with Fraser Health and the BC Care Providers Association. I hypothesize that participants in the intervention group will show greater improvement in measures of mobility, falls efficacy, and fall incidence. I will work with partners to refine my research objectives and disseminate results at the end of the trial. Findings will be shared through presentations, workshops and publications. By sharing best practices for mobility and physical activity promotion, I ultimately want to impact the older men who are in assisted living.
Pre-diabetic individuals exercise less than their non-diabetic counterparts, with less than 15 percent meeting Canada’s physical activity guidelines. Behaviour change techniques (BCTs) such as self-monitoring and provision of goal feedback are key components of interventions for cardiovascular risk factor reduction. However, patients in such programs may not accurately interpret risk information and fail to act in ways that reduce or prevent risk. Individuals at risk for type 2 diabetes (T2D) who exhibit biased thinking (e.g. all-or-nothing thinking; “Going for walks is not going to prevent me from getting T2D”) may not be ready to engage in risk-reducing behaviours. For this reason, reframing biased thoughts may offer a critical pre-intervention (pre-IV) step that prepares them for future attempts at behaviour change.
The purpose of this study is to examine cognitive reframing as a pre-IV strategy for individuals at risk of T2D about to embark on a brief exercise counselling intervention. The main hypothesis is pre-IV cognitive reframing will increase:
- Individuals’ self-regulatory efficacy
- Compliance with brief exercise counselling
- Independent exercise adherence
Cognitive reframing is an evidence-based strategy for reducing biased thinking in health contexts whereby individuals are taught to identify and challenge biased thinking caused by cognitive errors. This study will employ a randomized experimental design (intervention VS control group) to examine the effectiveness of pre-IV reframing for individuals at risk of T2D who experience biased exercise thoughts. The proposed research will be embedded within Dr. Mary Jung’s ongoing randomized control trials examining brief behavioural change IVs for people living with prediabetes in the community.
Results will partly be disseminated by coordinating a community-based prediabetes exercise clinic within Kelowna, and by working directly with Interior Health, the Kelowna Diabetes Program, and the Central Okanagan Division of Family Practitioners.
This novel research program seeks to triage individuals at risk of T2D with biased exercise thoughts. Findings may better prepare individuals with prediabetes struggling with a lifestyle change to be more receptive to receiving BCTs and attempt risk-reducing behaviour.
Hip osteoarthritis is prevalent, disabling and costly to individuals and the healthcare system. Symptomatic hip osteoarthritis affects 4.2 percent of people over 50, and radiographic degenerative changes are seen in almost 20 percent of the same population. In many patients, total hip arthroplasty is used to relieve pain and improve function. Though effective in improving a patient’s quality of life, joint replacements will eventually fail and require revision surgeries that have a higher complication rate and less predictable results. Better strategies to delay or stop the progression of osteoarthritis are needed, which can only be created with a clearer understanding of the disease’s etiology.
While there is strong evidence that structural changes around the hip are major etiological factors in the development of osteoarthritis, it is not clear how to protect hips from the disease. Anatomical abnormalities such as cam-type femoroacetabular impingement (a deformity of the hip bones) may account for 90 percent of hip osteoarthritis cases. However, it is not clear why only some people with these deformities get hip osteoarthritis. It is widely assumed that the relationships between activity and deformity size and their effect on joint mechanics are critical. Investigating these relationships has not been possible to date because there have been few well-validated methods for assessing impingement directly in vivo. This project will answer two research questions:
- Which activities lead to direct cam impingement at the hip in patients with FAI deformities?
- How is this impingement influenced by deformity size?
To answer these questions, we will use gait analysis to measure hip movements and mechanics in symptomatic and healthy subjects for a range of activities associated with hip pain. These measurements will be used to develop subject-specific numerical models predicting direct impingement for each participant. Model predictions of direct impingement will be validated by scanning participants using an established protocol in UBC’s upright open MRI scanner.
We have developed a knowledge translation strategy for this project with the Arthritis Patient Advisory Board; they will post the project summary on their website as well as profile the research findings on social media. Results will be published in both clinically- and research-oriented journals and at conferences for both clinicians and scientists.
One in eight men will be diagnosed with prostate cancer in their lifetime. Advances in prostate cancer treatments mean that the number of prostate cancer survivors is higher than ever; however, prostate cancer treatments come with side effects, many of which are life-long. Up to 90 percent of prostate cancer survivors will go on to experience erectile dysfunction (ED) — difficulties obtaining/maintaining an erection sufficient for sexual activity that can be highly distressing for both men and their partners. Although some medical treatments for ED exist (e.g. Viagra), these medications tend not to be very effective for these men.
Mindfulness (non-judgmental present-moment awareness) is a new tool in sex therapy that has been shown to be effective in treating women with sexual dysfunction. Mindfulness has also been shown to have psychological and physiological benefits for men who have survived prostate cancer (for example, it improves quality of life as well as immune system functioning in these men). The current research study aims to take the same mindfulness-based sex therapy that is effective for women, and adapt it for men with ED following prostate cancer treatments and their partners.
Men experiencing ED following prostate cancer treatment will be recruited from the Vancouver Prostate Centre to take part in a mindfulness-based group therapy. Men will be randomized to either an immediate or a delayed treatment group. The group will consist of six to eight other men and their partners, and involves two-hour sessions for four consecutive weeks, with home practice activities in between sessions. Content of the sessions will include education, elements of sex therapy, and mindfulness training. We predict that mindfulness therapy represents a new and important treatment that will ultimately help improve quality of life in the growing number of men who experience ED following prostate cancer treatments.
This project will examine optimal combinations of psychological and medical care for men with ED following treatment for prostate cancer and their partners, with the ultimate goal of improving conceptualization and treatment. In order to increase men’s access to sexual health care, knowledge translation is pivotal. I will collaborate with Dr. Lori Brotto and Dr. Tia Higano to share the findings with academics (e.g. conferences, publications) and stakeholders (e.g. media), and train clinicians to deliver MBCT for men (e.g. clinical psychology students at UBC, paraprofessionals in sexual health clinics across UBC and Vancouver hospitals).
Alzheimer’s disease causes progressive neurological decline and substantially decreases the quality of life of patients and their caregivers. In 2011, 747,000 Canadians had Alzheimer’s disease or another form of dementia. With a rapidly aging population, this figure is projected to rise to 1.4 million by 2040, costing $293 billion/year, thus representing an urgent and rapidly growing healthcare issue.
Early and accurate diagnosis of Alzheimer’s disease is critical because timely access to healthcare and community services has the potential to slow disease progression and improve quality of life. Current approaches for diagnosis rely on traditional imaging tests and observation of the signs and symptoms of the disease. Adding the measure of proteins found in cerebrospinal fluid (biomarkers) helps doctors correctly identify the disease. This project aims to create better tools for timely diagnosis of Alzheimer’s disease and other dementias, and make these tools easily accessible to those that need them.
This program of research will develop a comprehensive understanding of how biomarkers for Alzheimer’s disease impact clinical decision making and healthcare costs. It will develop an Alzheimer’s disease diagnostic tool and with input from patients, their families, their doctors and other relevant stakeholders, address barriers to uptake and use in the healthcare system. In addition to Alzheimer’s disease, this research will investigate development of diagnostic technologies for related disorders such as frontotemporal dementia and Lewy body dementia.
The ultimate goals of this work are to build a diagnostic platform for early detection and diagnosis of cognitive impairment; establish BC as a leader in neurodegenerative diagnostics; and ease the psychological, physical and financial burdens for people with dementias and their families.
Medications ideally improve patient health, occasionally with mild or moderate side effects. But sometimes patients have significant damaging responses to drugs, events called adverse drug reactions (ADRs). In Canada, there are 87,000 – 200,000 debilitating or life-threatening ADRs, which cause 3,600 – 10,000 deaths each year. The problem is worse in children, where ADRs are three times more life threatening than in adults.
The treatment of childhood cancer is especially impacted by ADRs: a staggering 73 percent of childhood cancer patients develop chronic health conditions from their treatment and 42 percent experience a disability or threat to life.
By better understanding debilitating and life-threatening ADRs in childhood cancer treatment, and generating ADR-predictive tools and prevention strategies, this project aims to benefit the lives of thousands of children and families. Over the past 10 years, collaborations with clinicians, policy makers, and industry partners have generated a sample pool of well-characterized patients for a group of priority ADRs.
This research program will analyze patient DNA to identify genetic factors that help predict ADRs. These will be validated through functional and mechanistic studies. Rapid and cost-effective lab tests will be developed to identify patients at high risk of severe ADRs. Moving knowledge into practice, clinical guidelines will be developed and drug label changes will be pursued, where appropriate, based on the findings.
Ultimately, this work will enable new strategies to protect patients from ADRs. For example, it should be possible to re-purpose certain drugs or use alternative treatment regimes in cases where predictive tools detect a risk of certain ADRs.
