Research Location: St Paul's Hospital

Bridging the gap: screening for fontan associated liver disease (FALD)

One in 3,000 children is born with one, instead of two, heart pumps, and as a result of a surgery called the “Fontan”, survive well into into adulthood. This surgery creates an artificial path that collects blood low in oxygen from the veins and sends to the lungs (instead of using a right heart pump) to pick up oxygen; leaving the single pump to send blood with oxygen to the body. We are learning these patients are developing many issues in adulthood including liver disease. The best way of identifying significant liver disease is through a liver biopsy, but it is not reasonable to perform biopsies regularly. We do not know the best way to easily identify and monitor liver disease in the Fontan population, yet this knowledge is critical to maintaining Fontan liver health, reducing co-morbidities ultimately benefiting our health care system. The first part of the study will be undertaken at St.Paul’s Hospital and Mazankowski Heart Center in Edmonton. We will perform a number of liver related blood tests/imaging to determine the best combination that identifies significant liver disease as diagnosed by liver biopsy. The second part will take place at five adult sites across Canada and will confirm our findings from the first part.

Familial hypercholesterolemia patient engagement forum: Family care and women’s health

Familial Hypercholesterolemia (FH) is the most common inherited disorder, with a prevalence of 1 in 250 Canadians, characterized by lifelong elevation in blood cholesterol leading up to 22-fold increased risk for heart disease. Despite this, in BC alone, more than 85 percent of cases are undiagnosed and only a minority receive appropriate treatment. A key component for improving care for this population is by increasing awareness through patient education, engagement and dissemination of recent FH research results. The purpose of this proposal is to organize an updated educational forum on FH, focusing specifically on family-based care and women’s health, including lectures by patients, physicians, dietitians and genetic counsellors, and interactive group sessions including patients’ testimonials. This forum will provide an opportunity for patients to learn about new developments in diagnosis and treatment of FH, including management in special populations, such as pregnant women and children. The goal is to empower patients to become advocates for the FH community by increasing awareness of the disease and recognizing the importance of screening their families for early identification, treatment and ultimately heart disease reduction.

Team members: Iulia Iatan (UBC, Centre for Heart and Lung Innovation); Nancy Pratt-Najera (St. Paul’s Hospital); Lubomira Cermakova (St. Paul’s Hospital, Healthy Heart Program Prevention Clinic); Durhane Wong-Rieger (Canadian Organization for Rare Diseases).

Determination of the optimal SARS-CoV-2 vaccination strategy to achieve a robust and long-lasting immune response

Global COVID-19 vaccine distribution has been inequitable, with high-income countries afforded widespread access to vaccines and boosters, while among the low-income countries only 2 percent of individuals are vaccinated. Consequently, over 50 percent of the world’s population remains unvaccinated. Fortunately, however, data from vaccinated cohorts can inform the most efficient and effective community-level vaccination strategies for the unvaccinated populations. Currently approved mRNA vaccines were initially tested with dosing intervals of 21-28 days; however, this may lead to suboptimal immunity. Further, data informing the optimal timing and frequency of booster doses is lacking. This project will answer critical questions regarding the optimal vaccination strategies to achieve a robust long-lasting immune response. In this study I will employ data from a prospective national cohort of adult paramedics, providing sociodemographic data and serum blood samples. I will identify the optimal vaccination strategies to achieving a robust immune response at 12, 18 and 24 months, including examining differences between sex, race, and age. These data will inform ongoing global vaccination efforts, to maximize efficiency and long-term protection.

Translating research into practice: Investigating the impact of Alzheimer’s disease diagnostics in Canada (IMPACT-AD)

Health Research BC is providing match funds for this research project, which is funded by the Brain Canada Multi-Investigator Research Initiative (MIRI) ā€“ Improving Health Outcomes and Quality of Life. Additional support is provided by UBC Faculty of Medicine, Djavad Mowafaghian Centre for Brain Health, and Women’s Brain Health Initiative. The research is also being undertaken in collaboration with the Canadian Consortium on Neurodegeneration in Aging.

 

Early and accurate diagnosis of Alzheimerā€™s disease is critical as timely access to health care 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) has been shown to help correctly identify the disease and predict those with mild symptoms that are likely to progress to dementia; however, such testing is not readily available in Canada.

 

The IMPACT-AD study specifically addresses barriers to uptake and use of Alzheimerā€™s disease biomarker testing in the Canadian health care system. This Canada-wide study will develop a comprehensive understanding of how biomarkers for Alzheimerā€™s disease impact clinical decision making and health care costs. Collaborating with patients, caregivers, and physicians, IMPACT-AD will also investigate the effect of testing on personal decision-making. The findings of this study will lay the necessary groundwork, modernize, and improve the care available to Canadians affected by Alzheimerā€™s disease and related forms of dementia.

 

IMPACT-AD is led by Dr. Mari DeMarco, a clinical chemist at St. Paulā€™s Hospital,Ā and a clinical associate professor in Pathology and Laboratory Medicine at UBC.Ā DeMarco is joined by a multidisciplinary team that includes both Canadian and international laboratory medicine specialists, geriatricians, neurologists, health economists, rural/remote clinicians, ethicists, and statisticians.

 

For more information about the study and how you can get involved, visitĀ www.impactAD.org.

Award update: December 2021

Delivery of self-management through a peer-support telehealth intervention in patients with cardiovascular disease: The Healing Circles Project

Health Research BC is providing match funds for this research project, which is funded by CIHR’s eHealth Innovation Partnership Program (eHIPP).

 

Cardiovascular disease (CVD) is a leading cause of death and disability in Canada, resulting in an estimated $22.2 billion in health care costs and lost productivity annually. Older adults are afflicted more than any other population, with many dealing with complex chronic conditions in isolation.

 

Patient self-management has been found to play a key role in improving patient health and reducing hospital admissions. Correspondingly, social and peer support, and timely access to credible information on managing CVD, are essential for patient self-management and quality of life. Over a four-year period, Dr. Scott Lear, a professor in the Faculty of Health Sciences and the Department of Biomedical Physiology and Kinesiology at Simon Fraser University, and his team based at St. Paulā€™s Hospital, will study the use of a new application, Healing Circles, that offers support to seniors with CVD while staying in their homes and communities.

 

Healing Circles is a private and secure peer support and self-management platform created through a partnership between university-based researchers, industry, decision-makers, clinicians and patients. The Healing Circles application, accessible on smartphones, tablets, and desktop or laptop computers, was developed by Curatio, a digital mobile health company, headquartered in Vancouver. Expansion of the use of Healing Circles by seniors with CVD builds on Learā€™s pilot study of the application involving women with heart disease from across Canada. After ten weeks, the women reported being better able to manage their health through the peer support and knowledge gained.

 

Healing Circles Project participants form virtual ‘Circles’ with 8 to 10 other patients to connect with and support one another as they learn to live day-to-day with their CVD. Additionally, the 250 study participants can interact with all members of the wider Healing Circles community to share experiences. Investigators anticipate that CVD patients using the Healing Circles platform in their homes will have improved self-management skills compared to patients receiving usual care, and improved quality of life, preventing secondary complications and reducing the need for health care and hospital use.

Understanding a potentially common upper airway disorder: Empty nose syndrome

Empty Nose Syndrome (ENS) is thought to be an unusual outcome of sinus surgery due to excessive loss of nasal tissues, particularly from a pair of structures called the inferior turbinates. Turbinates usually function to warm and humidify air flowing into the nose. Patients with ENS often have severe nasal symptoms and develop very poor quality of life as well as mental health problems. As a result of these mixed symptoms, ENS patients are often misdiagnosed, mismanaged, and left to their own devices.

Our research has shown that ENS patients can be identified based on specific clinical symptoms and imaging of the sinuses. We have also found that by rebuilding structures within the nasal cavity known as inferior turbinate augmentation (ITA) we can greatly improve nasal function. However, little is known about the specific changes in nasal function with ENS, how mental health problems develop, or how to best treat these patients.

Our objectives are three-fold: 1) to measure the patterns of nasal airflow and sense of smell present in ENS patients by using computer analysis and smell testing; 2) to understand how ITA might improve function in ENS patients by measuring nasal airflow and sense of smell before and after surgery; and 3) to study the impact of ENS on mental health using depression and anxiety survey scores, and then measure the change in these scores after ITA to study the relationship between the nasal and mental health problems in ENS. By studying the relationship between nasal and psychiatric symptoms in ENS we will both improve our understanding of how this syndrome develops and improve our understanding of how surgical interventions might help mend these symptoms.

Understanding the aging HIV lung from dysbiosis to cell injury

Patients with human immunodeficiency virus (HIV) are now living to older ages thanks to effective anti-HIV medicines. Despite these gains, many of them suffer from chronic lung disease that greatly impacts their ability to carry out their daily activities and impairs their quality of life. The type of lung disease they face is similar to what longtime smokers develop, a progressive narrowing of the airways and destruction of the lung. However, in HIV, the process appears to be accelerated and more severe. It’s not unusual, for instance, to see patients in their 30s and 40s develop this lung disease (which is approximately 30-40 years earlier than expected). Also, it’s not unusual for HIV patients who have never smoked before to develop this kind of disease. Unfortunately, the traditional medications we use to treat lung disease often interact with anti-HIV medicines, causing severe side effects. Management of breathing symptoms in HIV patients is therefore difficult and it is imperative that we find better agents to combat lung disease in this population. Only by understanding what causes and drives this lung injury process can this goal be achieved, though.

Multiple studies have now shown that smoking alone cannot explain the lung disease phenomenon in HIV. I believe that HIV injures the lung in a two phase process. First, the virus directly breaks down the protective layer of the airway known as the epithelium. Second, over time, as patients develop repeated lung infections due to their weakened immune systems, the bacterial community of the lung or microbiome shifts. I believe that this community disruption results in molecular changes that age the lung faster. My approach is to perform an in-depth investigation into the epithelium of the airway using two innovative methods. To explore the injury that HIV inflicts on the airway, I have created a novel model of the HIV airway using HIV-infected cells co-cultured on a cell culture model of the airway epithelium. We will use this model to see how HIV-infected cells break down the protective barrier of the lung. To explore the shifts in the microbiome, I have collected airway cells from HIV-infected and uninfected patients to not just describe what bacteria exist in the airway but also to determine what effect the community differences between the two groups have on the function of genes in the cells. We will measure how ‘old’ these cells are and compare these findings to uninfected patients.

End of Award Update: December 2022

 

Most exciting outputs

The work of my laboratory was the first to detect accelerated epigenetic aging and methylation disruptions in the HIV airway epithelium, work that has now been published in the American Journal of Respiratory and Critical Care Medicine, and eBioMedicine.

 

Impacts so far

These insights into accelerated aging in the HIV airway epithelium provide clues into why people living with HIV may be prone to developing chronic lung diseases such as Chronic Obstructive Pulmonary Disease or COPD.

 

Potential future influence

Our work highlights the importance of accelerated aging in HIV, even in patients with well controlled infection. Reversing these aging mechanisms may be critical in the prevention or attenuation of airflow obstruction in this population.

 

Next steps

We are continuing to explore mechanisms of early aging in the HIV airway using novel technologies such as magnetic resonance imaging, optical coherence tomography, and single cell sequencing.

 

Useful links

Developing personalized anti-arrhythmic drug therapy for atrial fibrillation

Atrial fibrillation (AF) is the most common heart rhythm disorder. With an aging population, the number of people with AF is expected to rise dramatically. People with AF are twice as likely to die, are five times more likely to have a stroke, can develop worsening heart muscle function, and have a lower quality of life. We have learned that a person's genetic makeup, or DNA, has a major impact on their risk of developing AF; but we have a limited understanding of why, or how to use this information to treat people in a safer and more effective way. People with AF first receive drugs to control their irregular heart rhythm. Even people who have procedures to treat AF are also prescribed drugs. This is particularly important in the group of patients who have persistent AF, who require electrical or chemical therapy to change their heart rhythm, as the success of surgical procedures in this population is well below 50%. Unfortunately our current drugs are generally ineffective, and can be unsafe, with little progress in drug development over the last two decades.

With these challenges in mind, the first goal of my research program is to identify and understand the genes that play a role in the development and progression of AF, and determine which are most common and most important in the Canadian population. To do this, I am gathering a biobank of AF patients and performing the largest scale detailed genetic testing in this population to date. I am also focused on understanding the effect that genes can have on the safety and efficacy of rhythm controlling drugs, and have already started a trial, funded by the Canadian Cardiovascular Society, that will link a person's genetic makeup to these important outcomes. I will then be able to take this large clinical and genetic data set to the laboratory where we have developed the unique ability to generate patient-specific stem cell disease models of AF. The ultimate goal of my research program is to directly tailor therapy for AF patients based on their genetic makeup, using information from clinical research and personalized disease modeling.

 

Addressing morbidity, mortality and health care costs among patients evaluated for addiction care in acute care settings

Substance use disorders account for a significant burden of disease among Canadians and place an enormous burden on the acute care system. The annual cost of harms associated with substance use in Canada is estimated to be approximately $40 billion, with health care being the single largest contributor. In British Columbia (BC) there is clear urgency to address this challenge, given the recent steady increase in hospitalization rates due to substance use and the unprecedented number of drug overdose deaths prompting the recent declaration of a public health emergency.

While in hospital, individuals with a substance use disorder often have access to evidence-based addiction care, though successfully transitioning these individuals from acute to community settings remains a key clinical and research challenge. Specifically, this patient population often leaves hospital against medical advice, may be non-adherent to addiction care recommendations and often requires costly repeat hospital readmissions. Addressing these circumstances is critical, given the enormous cost implications and opportunity for more effective addiction services to dramatically reduce morbidity and mortality.

Specifically, investigating acute substance use needs and long-term solutions in acute care through after-care environments presents an urgent clinical health research priority given the frequent intersection between individuals with a substance use disorder and hospital environments. To address this, the proposed research project will establish a prospective cohort study of hospitalized individuals with a substance use disorder who are assessed for treatment of their addiction. Individuals will complete a one-time questionnaire and provide consent to the use of their personal identifiers for linkage to a variety of health care databases to allow for ongoing community follow-up over a five-year period. Creation of this study will offer the unique opportunity to identify patient characteristics of individuals accessing addiction care in the hospital setting, evaluate patient flow and predictors of outcome between hospital and community settings and determine subsequent health outcomes and health care utilization. In doing so, this research platform will generate evidence that will contribute to future interventions and knowledge advancement, and help inform best practices for the optimal delivery of addiction treatment to this population with high morbidity and mortality.

Understanding the spatial and contextual inequities of health access and use by people living with or vulnerable to HIV in British Columbia

Access to health care services is critical to improving the health and well-being of people living with or vulnerable to HIV. Factors such as density of services or neighbourhood violence play a substantial role as barriers or facilitators to health care access in broader populations, but limited research is available to show that this is also true for people living with or vulnerable to HIV. This study will investigate, within BC:

  1. The distribution of access and use of health services, especially health services in HIV testing and treatment.
  2. The barriers and facilitators related to access.
  3. How to develop a rigorous methodology to capture, quantify and analyze data on access and use of health services.

The proposal will draw data from several large, multi-year studies conducted by the BC Centre for Excellence in HIV/AIDS and will link to external datasets for the development of key measures. This project will focus on analyzing data regarding health care services utilization across different regions in BC over time. The proposal aims to improve access to services for earlier diagnosis and improved treatment for people living with HIV.