Two out of every five individuals will develop cancer during their lifetime. My research program focuses on cancer prevention and diagnosis, using skin cancer as an initial platform. Skin cancer accounts for two thirds of all cancer cases and is an easily accessible organ to study using optical devices. Biopsies are typically used to detect skin cancers. Disadvantages of skin biopsies include possible disfigurement and complications, lengthy processing time, and occasionally inaccurate or inconclusive results. As well in some patients that are at high risk, taking multiple biopsies may not be practical and is costly. In this proposal, we will determine if an optical device combining different optical methods can readily and accurately detect skin cancer.
Ultimately, we expect this optic device to provide a noninvasive and instantaneous diagnosis that would be available to the patient and clinician at the bedside. This novel method of combining different spectroscopy methods to be able to collectively evaluate skin lesions and help in the diagnosis of skin cancer would be a significant achievement in the screening of cancer. Early and improved detection using a noninvasive method would help to improve morbidity and mortality in those affected with cancer.
Aggressive B-cell lymphomas are the most common form of lymphoma and ~50% of patients are cured with modern treatments. However, the outcomes for patients whose disease is not cured are dismal with ~10% of those patients alive at 5 years. This shows that these lymphomas, although grouped together on the basis of what they look like down the microscope, represent clusters of different lymphoma groups. A better understanding of the 'molecular wiring'of these lymphomas is critical to identify patients at high risk of resistant lymphoma and providing better treatments.
This project will provide a rational new way to group lymphomas based on differences in the molecular wiring. This will be acheived by performing and analysing genomic sequencing on a large number of aggressive B-cell lymphomas brought together through an international lymphoma consortium. Further, tumour samples will be analysed from the time of diagnosis and when the lymphoma relapses to see whether this molecular wiring remains stable or changes with treatment. It is anticipated that this major step forward in our knowledge will be translated into new tools for matching a patient's lymphoma to the correct treatment and improving patient outcomes.
Spontaneous coronary artery dissection (SCAD) occurs when there is a tear in the inner layers of a blood vessel in the heart, causing blockage and reducing blood flow and oxygen to the heart. It is an emergency condition that can result in heart attack and even death. Unfortunately, the causes of SCAD are poorly understood, and it is often misdiagnosed and mistreated.
This disease is very concerning because SCAD affect mostly young, otherwise healthy individuals, particularly women. The objective of our study is to enroll and follow 3,000 women and men who have suffered a heart attack as a result of SCAD. These patients will be recruited from across Canada, the United States, and internationally. This will be the largest and most comprehensive study on SCAD in the world.
We will follow them for up to 10 years and evaluate how their initial treatment (surgery, stenting, or medication) affects their in-hospital recovery and long-term health outcomes. We will also assess for underlying causes of SCAD that include pregnancy or abnormal growths causing narrowing of the walls of the arteries. We will also perform genetic tests in a large subset of these patients to determine if there are genes we can use to screen off-springs of patients. We will also examine how these conditions can affect the future risks of cardiovascular events, such as another heart attack, stroke, or death. This innovative research study will help generate guidelines to diagnose, investigate and treat SCAD.
Interstitial lung disease (ILD) is a progressive lung disorder with no effective treatment. Oxygen is often used to relieve symptoms at the end of life, but the evidence supporting oxygen use in these patients is based on limited data from other diseases. The lack of data on the benefits of oxygen in patients with ILD has resulted in uncertain criteria for its use and limited access to this potentially important medication.
My proposed research includes a detailed evaluation of the clinical, biological, and prognostic impact of oxygen in patients with ILD. My main objectives are to determine (1) the rate of progression and prognostic significance of low oxygen levels in patients with ILD, (2) the clinical and biological benefits of night-time oxygen in patients with ILD, and (3) the impact of oxygen on the use of medical services in patients with ILD and other forms of chronic lung disease.
This research will provide a thorough understanding of the role of oxygen in patients with ILD. These findings will inform patients, physicians, and policy makers on the appropriate use of oxygen in this setting, with additional components of this research that are aimed at identifying potential mechanisms of ILD worsening.
Acute kidney injury (AKI) complicating critical illness is an important problem, contributing to roughly 1.7 million deaths worldwide per year. Treatment is limited to dialysis, which is costly and frequently unavailable. Preventing AKI is a critical step to reduce deaths. Acetaminophen (Tylenol) has the potential to reduce AKI caused by oxidative damage from hemoglobin (released from red blood cells) and myoglobin (released from muscle cells). Acetaminophen inhibits this oxidative damage and reduces kidney dysfunction in animal models, and in patients after cardiac surgery or in patients with sepsis.
I previously led a trial in adults with severe malaria showing that acetaminophen improved kidney function and reduced the odds of developing AKI. Since children bear the major burden of malaria, it is crucial to test this protective effect in African children where 45% of patients have AKI. The goal is to assess the role of acetaminophen as a kidney protective therapy in severe malaria.
I will conduct a randomized controlled trial of adjunctive acetaminophen in African children with severe malaria. If the trial is positive, the results would change severe malaria management globally. It could be rapidly scalable as acetaminophen is inexpensive, safe and widely used. These findings will have broad implications for other major causes of hemoprotein-mediated AKI including crush injury and sepsis, which directly impact thousands of Canadians.
Deaths due to opioid overdoses have reached epidemic proportions in Canada, with nearly 8,000 Canadians losing their lives in the last two years. Knowledge of how rescuers can best respond to cardiac arrests due to opioid overdose is urgently needed.
Unfortunately, there is a paucity of studies examining opioid-related cardiac arrest; therefore, there is a lack of evidence to guide bystanders or professional rescuers on how best to intervene. Specifically, there is controversy regarding the benefit of bystander-initiated rescue breaths and paramedic-delivered naloxone. The goal of this project is to determine best resuscitative strategies for opioid-related cardiac arrest to inform national and international guidelines.
In this project I will create the largest and most comprehensive dataset of cardiac arrest cases due to opioid overdose in the world, complete with detailed data on bystander and professional interventions, and patient-oriented outcomes. I will analyze this data to determine the best treatment strategies. In addition, I will examine the benefit of public access opioid overdose kits and their optimal locations. I will implement a knowledge translation and dissemination plan in collaboration with key knowledge-users.
Many patients with depression struggle to return to their full level of functioning in work and other areas of life. These poor functional outcomes in depression may be related to cognitive difficulties, as patients demonstrate problems with memory, attention, and problem solving. We however lack treatments for these difficulties. Cognitive training, consisting of tasks to target cognitive deficits, has been tested but shows inconsistent results in depression.
Virtual reality (VR) – which is immersive, interactive and can recreate real world settings – may enhance cognitive training. VR cognitive training has shown benefits in stroke and schizophrenia. However, a full course of VR cognitive training has not been tested in depression.
With the National Research Council Canada, we have designed a VR cognitive training suite, the 'bWell' Cognitive Care Platform for Depression. We plan to pilot bWell in patients. This will determine if bWell is feasible, and will allow us to gather patient feedback to improve the tasks. We will then proceed to a clinical trial comparing bWell to standard cognitive training in depression. Our goal is to determine if VR can improve cognitive and functional outcomes in depression.
Over 2.5 million Canadians have chronic obstructive pulmonary disease (COPD), which is a progressive lung condition that blocks the airways and makes it difficult to breathe. These patients experience worsening shortness of breath, increasing exercise limitation, and reduced quality of life. Patients must work harder to breathe, and the lungs can over-inflate, which can squeeze the heart and affect how it functions. Further, more than 1-in-4 patients also have high blood pressure, which might amplify the negative effects of lung over-inflation on the heart. This is important because cardiovascular issues contribute to exercise limitation and account for 25% of deaths in COPD.
This study will use non-invasive imaging and monitoring to measure heart function and blood pressure. First, to understand the direct effects of lung volume and blood pressure on the heart, we will study how lung over-inflation can affect heart function when blood pressure is normal or high in healthy adults by using temporary experimental increases in lung volume and blood pressure. Second, we will perform a similar study in patients with COPD, which will allow us to better understand why patients who have COPD are more affected by cardiovascular disease.
Falls cause up to 80% of traumatic brain injuries (TBI) in older adults. Any fall from standing may cause TBI if head impact occurs. Humans use movement strategies to avoid head impact during falls, such as 'arresting' the fall with the arms. Through video capture of real-life falls, we found that these strategies persist but become less effective for older adults in long-term care, with over 1/3 of falls resulting in head impact in this setting. This project continues our work with Debbie Cheong (Osteofit Provincial Coordinator at BC Women's Health Centre) to design and evaluate novel exercise programs for enhancing protective responses for avoiding head impact in falls. We will identify the strength and flexibility demands of common safe landing strategies observed in falls in older adults, and design and evaluate feasible approaches to enhance those capacities for older adults of varying physical and cognitive status.
This project will lead to new evidence on the strategies that older adults use to avoid head impact during falls, and the musculoskeletal demands of those strategies; new exercise-based approaches for targeting and enhancing the effectiveness of fall protective responses in older adults; and evidence of the feasibility and effectiveness of our exercise program for older adults.
Over 400,000 Canadians live with long-term disability from stroke. Stroke survivors say regaining walking ability is a top priority; but, poor cognition, or thinking abilities, can limit walking in the community. How much walking recovery someone achieves likely stems from the brain's ability to dual-task (DT), like walking while talking. In fact, almost 80% of stroke survivors struggle with some aspect of cognition limiting full walking recovery after stroke. The complex demands of community mobility after stroke can be studied in laboratory settings using DT, where walking is done with a cognitive task.
Using DT, studies have found the brain is crucial for DT, and that altered levels of brain activity affect DT ability. But, little research probes if stroke survivors could produce brain recovery with DT training, as neuroimaging methods like functional MRI, cannot collect data during standing and walking. Functional near-infrared spectroscopy (fNIRS) is an ideal imaging tool to assess walking without physical limits, but its utility to detect if DT training can drive the brain to recover walking has not been tested in stroke survivors. So, the goal of our clinical trial is to test if DT training can help the brain recover and allow for better DT ability. DT training may drive brain recovery by addressing cognitive and motor difficulties at the same time, maximizing rehabilitation efforts, and improve walking ability in the community after stroke.