Economic evaluation of the use of expanded criteria donor kidneys pre-emptively to improve the critical organ shortage

Kidney transplantation can be life saving for people with end-stage kidney disease at a lower cost than the only other alternative which is dialysis treatments. Unfortunately, there are not enough kidneys available for transplant. This means that until we can improve the kidney supply, patients will continue to have to wait on a waiting list and may die in the process.

Kidneys from older donors have been successfully used for transplant, but at a higher risk. This higher risk discourages some patients and physicians from accepting these kidneys for transplant. This results in kidneys being discarded that could otherwise have saved lives.

However, these kidneys will have better outcomes if they are given to patients before they ever need to start dialysis, instead of our current practice which is to wait until someone is at the top of the waitlist after years of dialysis. This research project will use economic models to study how allocating kidneys from older donors to some patients before they ever need dialysis might impact the overall kidney supply and patient outcomes. This research will help inform future health care policy which may improve organ supply for patients waiting for a life-saving transplant.

The DISCO study: Rethinking STI prevention

Syphilis, chlamydia and gonorrhea are three of the most common sexually transmitted infections (STI). Over the last decade, these STIs have seen a resurgence in many parts of Canada, with most infections seen in major urban centres. These infections have primarily affected gay, bisexual, and other men who have sex with men (gbMSM). Recently, a small pilot study found that doxycycline — an inexpensive, well-tolerated antibiotic — given daily may prevent new STIs in gbMSM. Another study looked at the use of doxycycline given after a sexual encounter for prevention of STIs, and the results of this study showed protection against STIs as well. Based on these promising data, along with the concerning increases in STIs seen in Canada, the current study will examine the use of doxycycline as either a daily prevention therapy (preexposure prophylaxis, or PrEP) or an ‘after sex’ prevention tool (postexposure prophylaxis, or PEP) for STIs in gbMSM. While examining for efficacy as its primary goal, this study will also do an examination of some of the potential challenges and concerns associated with the use of a daily antibiotic: drug resistance, tolerability and side effects, and how acceptable this drug is for people to take regularly.

Redesigning health care for concurrent disorders: The role of multimorbidity in complex co-occurring psychiatric and substance use disorders

Individuals with both psychiatric and substance use disorders, defined as concurrent disorders, are more complex to diagnose and treat due to several interacting health and social challenges. In the absence of appropriate treatment people with concurrent disorders are at high risk for increased morbidity and mortality. A growing body of evidence recommends abandoning the traditional single-disease health model in favour of a multimorbidity approach to care. Despite available evidence, important gaps persist in our understanding of how individual and health system context influence service utilization and outcomes for people with complex multimorbid disorders (e.g. concurrent disorders). The proposed research will establish a prospective cohort of individuals with a concurrent disorder. Individuals will complete a series of brief questionnaires and provide consent to use their personal identifiers for linkage to a number of health databases. This research offers a unique opportunity examine health outcomes associated with multi-morbidities and understand patterns of health care utilization overtime. This research will advance knowledge to inform best practices and service reforms for the optimal delivery of care in BC.

Evaluating the use of prescription psychostimulants for the treatment of methamphetamine use disorder

Crystal meth is a powerful stimulant that is increasingly implicated in the ongoing overdose crisis in BC. Despite steadily increasing rates of crystal meth detection in overdose deaths, little is understood about the specific role that it may be playing in the overdose crisis, and treatment options for those suffering from crystal meth use disorder (MUD) are limited.

One class of medications that has previously shown some promise in the treatment of MUD are prescription stimulants such as those used to treat ADHD. While research in this area remains inconclusive, there is some suggestion that these medications may play a helpful role in the treatment of MUD, especially among patients with an overlapping diagnosis of opioid use disorder.

This proposal will employ a variety of research methodologies to explore two related questions: (1) Can we identify patients who use crystal meth and opioids that are at particularly high risk of overdose, and (2) Are prescription stimulants a helpful tool in the treatment of MUD in a population of patients who use opioids? These results will have significant implications for both healthcare providers and those suffering from MUD, at a time where new tools are sorely needed.

Advanced pulmonary diagnostics in paediatric respiratory medicine: From technical development to clinical implementation

Chronic lung diseases present a serious health challenge for Canadian children and youth. For example, cystic fibrosis (CF) shortens life expectancy and carries an enormous treatment cost (>$250,000 per person per year). Another example is asthma, which affects nearly 1 in 7 Canadians under age 20. Improving the lives of people with these conditions is possible but requires accurate detection and close monitoring of their lung disease.

Unfortunately, the tests available to paediatric respiratory physicians are often difficult for children to perform and not sensitive enough to detect or subtle disease. This significantly limits physicians’ ability to detect, treat and monitor lung disease in children and must change.

My research program focuses on the development of easy-to-perform and sensitive tools to help physicians diagnose and monitor lung disease in children. Specifically, I am an expert in techniques known as hyperpolarised xenon lung MRI (XeMRI) and multiple breath washout testing (MBW).

During tenure of this Health Professional-Investigator award, I will lead research focused on improving the XeMRI and MBW techniques and using these new tools clinically to improve the health of children with lung diseases.

Leveraging computational modelling and 3D bioprinting in pursuit of a regenerative therapeutic approach for male infertility

A desperate need exists to develop technology to regenerate sperm that can be used for in vitro fertilization (IVF) among men who lack sperm production, such as pediatric cancer survivors. In Canada, approximately 2,440 boys aged less than 15 will be diagnosed with cancer each year. Fortunately, the field of oncology has made significant improvements in survival rates, which are estimated to be 83%. However, treatments will render up to 97% of paediatric cancer survivors infertile with no sperm production, despite over 75% eventually desiring to have biological children. While stem cells (sperm precursors) can be retrieved prior to cancer therapies, no technology currently exists to regenerate sperm, which is required to achieve a pregnancy. This project proposes to utilize single cell sequencing and along with state-of-the-art computational modelling to reveal molecules and pathways that are key regulators of developing sperm from stem cells. These findings will be screened and tested to identify critical molecules that help generate sperm in 3D bioprinted structures. Results from this study will contribute to developing the understanding and technology to regenerate sperm for men lacking any ability to father biological children.

Exploring oxidative phosphorylation as therapeutic vulnerability in high risk acute myeloid leukemia

The standard of care for AML patients was introduced in the 1970s and has not significantly changed since then. Patients suffering from acute myeloid leukemia (AML) with unfavourable genetics are characterized by dismal overall survival due to poor treatment response to standard chemotherapy. In this research proposal, I aim to better understand the energy metabolism of high-risk AML cells and explore this as a novel treatment avenue. My research will create a rational for future clinical trials to improve patient care and develop novel treatment perspectives for a patient collective with a bleak prognosis.

Design and pilot of a culturally resonant intervention to treat substance use disorder among South Asian men

Substance use disorder is a growing problem affecting racialized men in Canada. There is increased awareness and understanding about why and how racialized men use substances, yet little is known about effective treatments and interventions. The project will use anti-racist research methods to design and study an intervention to support a racialized group, South Asian men who use substances. The team will consist of Punjabi men who use substances, community organization members, health care providers, and researchers. Using a rigorous facilitated approach that highlights evidence from literature and draws upon members’ life experiences, the team will design an intervention to support South Asian men who use substances in the Lower Mainland. Once the design is complete, the intervention will be studied in a feasibility study and pilot randomized controlled trial (RCT) in preparation and justification for a full scale RCT.

Neuropsychological functioning in treatment resistant schizophrenia

Schizophrenia is a severe and disabling psychiatric illness involving primary symptoms of psychosis (hallucinations, delusions, disordered thinking and behavior). Unfortunately, as many as 30% of patients respond poorly to standard antipsychotic medications and are considered to have treatment resistant schizophrenia (TRS). Neuropsychological impairment is an important clinical feature of schizophrenia, as cognitive deficits predict poor treatment response, daily functioning, and disability. However, very little is known about cognitive functioning in the clinically complex subset of patients with TRS. The aims of this project are therefore to investigate the severity, pattern, and variation in cognitive functioning among individuals with TRS, and to determine whether cognitive difficulties predict treatment response and functioning. This will be achieved by analyzing clinical and neuropsychological data that has been collected on TRS patients who have been treated within the BC Psychosis Program since 2012. Findings using this unique dataset will have a direct impact on shaping assessment and treatment strategies, improving prognosis and ability to predict functioning, and improving clinical decision-making and planning.

Does timing matter? A trial of intermittent fasting in haematological malignancies

Does when we eat make a difference to our health? We know that food choices can impact cancer risk but what if the timing plays a role as well? Evidence shows that fasting may slow cancer growth through a process called autophagy. Through an interdisciplinary research team, I am currently running a small trial testing the effects of intermittent fasting (IF) in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) at BCC-Victoria who are not on anti-cancer treatment. Specifically, I am asking whether IF regimens, differing in fasting timing and duration, stimulates autophagy, improves quality of life, impacts gut microbiome, and/or results in clinical benefit (i.e. reduced lymphocyte count). I am also following participants’ safety, ability to follow the fast, and fasting preferences. While early results look promising, I propose growing this study into a larger trial with three phases to clarify the effects of IF on cancer and the microbiome. Understanding these effects may help discover simple diet recommendations for patients with cancer that cause a response in cancer cells or slow cancer progression, are safe and reduce treatment side effects when used alongside current, standard treatments.