How can we Improve Survival from Opioid-Related Cardiac Arrest?

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.  

Out-of-hospital-cardiac arrest: Care gaps and opportunities to improve long-term survival

Out-of-hospital-cardiac arrest (OHCA) affects 40,000 Canadians per year. Cardiac arrest is the sudden loss of heart beating, and can occur in people with or without known heart disease. In British Columbia (BC), only 15% of these patients live (50% die before hospital, 35% die in hospital), less than 50% receive bystander cardiopulmonary resuscitation, and only 3% receive bystander automatic external defibrillation. Due to a lack of connected data, little is known about the effect of treatments on long term survival, brain function and quality of life after leaving hospital.

We are closing this knowledge gap by having recently developed a new provincial database linking BC Ambulance records with hospital charts, prescription data, and post-discharge nursing home and home care information. This is the first database of its kind in North America and includes information for over 16,000 OHCA patients. We can now evaluate the complete 'journey' of each patient from 9-1-1 call, to hospital treatments, to survival and functional status long after discharge. We can now determine if current treatments affect length of survival, brain function, and quality of life, and within this framework, eventually test whether new strategies improve patient outcomes. 

Virtual Reality for Cognitive Training in Depression: the bWell Cognitive Care Platform

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.  

New strategies for unclogging microcirculatory obstructions in the healthy and diabetic brain

Recent work from our laboratory has shown that the brain capillaries routinely get 'stuck,' clogged by cells and debris even under healthy conditions. Most of these clogged capillaries clear within seconds to minutes, however, some can remain stuck for much longer. We also reported that about one third of these clogged capillaries were eliminated from the blood vessel network and never get replaced. Importantly, there are certain conditions which can increase the risk of clogged blood vessels in the brain such as diabetes. However, we still do not have a good mechanistic understanding of how these capillary obstructions can be cleared, or even what impact they have on brain function.

In this study, we will characterize capillary obstruction and pruning rates in healthy and diabetic mice brain. Next, we will focus on devising new strategies to enhance the clearance of capillary obstructions. At various time points, the mouse brain will be imaged to assess obstruction clearance and capillary elimination rates. These aims will provide new insights into microcirculatory changes that occur in healthy and diabetic brains, as well as a mechanistic understanding of how capillary obstructions can be cleared.

Making Healthy Connections: A Critical Anti-Racist and Decolonizing Geography of Immigrant and Indigenous Relations in Northern British Columbia

While resources support immigrant well-being in urban settings in southern Canada, little research exists on recent immigrants in northern communities. Moreover, while new research is emerging about the health disparities of Indigenous communities in remote and rural settings, there is very little research that brings the question of immigrant and Indigenous relations together.

To address this gap, this research program will determine factors that influence and support the well-being of recent immigrants in northern BC communities. The project will document, analyze, and provide much needed information about the unique social determinants of health for recent immigrants outside of large urban centres in southern Canada. I will engage recent Filipino immigrants using qualitative research methods and will establish and mobilize a community of experts and highly-trained practitioners to help provide a more nuanced, textured and richer picture of the health needs of northern BC.

Importantly, the research program will not only bring new awareness about the factors influencing health and well-being of Filipino immigrants, it will also explore these factors in relationship to health disparities and innovations of Indigenous northern communities. In sum, this is a project that puts Filipino and Indigenous communities in dialogue to address health disparities.

 

Disease-modifying Drug Safety and Effectiveness in Multiple Sclerosis [DRUMS]

British Columbia (BC) and Canada have some of the world's highest rates of multiple sclerosis (MS). The goal of this research is to find out how safe and effective the drugs used to treat MS are when used in the everyday, real world in BC and Canada.

To achieve these study goals, I have two main study Themes. The first Theme focuses on how effective the MS drugs are. I will examine whether the MS drugs can extend life expectancy or prolong a person's ability to stay mobile and walk. I will also look at whether the MS drugs have a beneficial effect on reducing the number of times a person with MS is admitted to a hospital or visits a physician. The second Theme focuses on side effects, including whether the MS drugs are associated with harmful effects, such as cancer, stroke or depression. I will be able to compare the different MS drugs to each other. Also, I will see if men and women or people of different ages and with other illnesses (such as having both MS and diabetes) respond to the MS drugs differently.

My research findings will help people with MS and their physicians when trying to make decisions as to which MS drug might be best for them. Ultimately, this study will benefit the >90,000 people living with MS in Canada.

Structural basis of novel strategies for the inhibition of AmpC-mediated beta-lactam antibiotic resistance in the opportunistic, nosocomial pathogen Pseudomonas aeruginosa

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen often responsible for hospital-acquired infections, which can be very difficult to treat due to antibiotic resistance. A common mechanism of resistance is the expression of beta-lactamase enzymes, which break down and disarm classical beta-lactam antibiotics, such as penicillins. Beta-lactam antibiotics act by breaking down the bacterial cell wall, producing cell wall fragments that induce expression of the beta-lactamase, AmpC. In many Gram-negative bacteria, AmpC base expression is low but can be induced by exposure to beta-lactams. Current beta-lactamase inhibitors are ineffective against AmpC, therefore blocking upregulation is a potential strategy to combat the resistance effects. AmpG, a transporter that imports the cell wall fragments needed for AmpC expression, is an exciting new target. This project aims to solve the first atomic resolution structure of AmpG and further our understanding of how the transporter functions. This project has the potential to translate directly into the development of new AmpG inhibitors and treatment strategies that preserve the effectiveness of current antibiotic therapeutics in the clinic and community.

Impact of Hypertension on Lung-Heart Interaction in Patients with Chronic Obstructive Pulmonary Disease

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.

Can Blending Western and Traditional Knowledge Improve Diabetes and Obesity Health in Urban Indigenous Communities?

Indigenous peoples in Canada suffer from significantly higher rates of diabetes and obesity, resulting in reduced quality of life. There is often a lack of Traditional knowledge and community leadership within health, government, and community organizations. The impact of Western care services on improving health are often limited, whereas inclusion of Indigenous community-led care services has shown to improve health. Our current study will co-develop, co-implement, and co-evaluate locally-informed, culturally relevant diabetes and obesity programs in six urban/rural Indigenous Centres. The aim of the study is to blend Traditional and Western knowledge to improve diabetes and obesity services in urban/rural Indigenous communities.

Throughout the project, Community members and Advisory teams will identify needs and solutions for community specific interventions. The proposed will explore the effects of community programs on participant clinical diabetes and obesity measures. Knowledge translation activities will include community gatherings, presentations, publications, and adaptable program platforms. Knowledge gained from this will inform health policy, research, and practice for urban Indigenous communities.

Investigating components of a Campylobacter jejuni iron uptake system to inform antimicrobial strategies.

Campylobacteriosis is an infectious diarrheal disease and one of the largest contributors to hospitalizations and deaths from food poisoning in Canada and worldwide. It is usually caused by consumption of food or water contaminated by the bacterium Campylobacter jejuni, resulting in watery or bloody diarrhea, fever, and serious post-infectious illnesses. This illness is especially dangerous for very young or old people, made worse by lack of a vaccine and increasing frequency of infections that are resistant to treatment by current antibiotics. A recent WHO report identified C. jejuni as a pathogen with a 'high priority for research and development of new antibiotics'. To thrive and cause campylobacteriosis, C. jejuni must take up nutrients such as iron, which is present in the human gut.

This project will investigate the structural components of a newly-identified system which helps this bacterium collect iron from its surroundings during infection. Better understanding these structures could allow us to develop new antibacterial agents which fight infection by preventing the bacterium from collecting iron. These outcomes could be extended to several other disease-causing bacteria which contain related iron-collecting systems.