Linking administrative and survey data to examine substance use related diagnoses, hospitalization and mortality among gay, bisexual and other men who have sex with men in Metro Vancouver

Every day, over 400 Canadians are hospitalized because of drug and alcohol-related causes. These admissions are widespread, costly and deadly. This issue is especially problematic in British Columbia (BC) where hospitalizations related to alcohol abuse are highest in the country. Population data consistently highlight that licit and illicit substance use is more common among gay, bisexual and other men who have sex with men (GBM) compared with heterosexual individuals. However, research assessing substance use related mental and behavioral disorders, hospitalizations and mortality is lacking for GBM due to the lack of identifiers for sexual orientation in administrative research. This study links administrative and survey data to examine substance use related outcomes from 2012 to 2020 and compare these rates between GBM and heterosexual males in BC. Further, we will use cohort survey data to examine behavioural and structural factors associated with substance use related disorders, hospitalizations and mortality among GBM in BC. Our results will inform recommendations to improve substance use healthcare for GBM and support reductions in hospitalization costs related to substance.

Walking away from depression: Leveraging physical activity to treat symptoms and improve well-being in individuals with major depressive disorder

Major depressive disorder (“MDD”) is a chronic condition characterized by sadness and loss of pleasure. MDD is a leading cause of disability (WHO, 2020), and costs the Canadian economy billions each year (CAMH, 2021; CASHC, 2016). In 2016, the Canadian Network for Mood and Anxiety Treatment recognized exercise as a first-line treatment for MDD. This statement should have revolutionized care: not only does exercise reduce symptoms, but it also improves health and quality of life. However, the past five years have seen little progress in “mainstreaming” exercise as a treatment option. This means patients are being denied access to a safe and effective treatment.

We are left with a question: How can we get more people with MDD more active more often?

The purpose of my postdoctoral fellowship is to answer this question. I will oversee a program of research that examines how British Columbia’s public health system can provide exercise as a treatment for MDD. I will investigate barriers to uptake; strategies to overcome barriers; and engage in program development and evaluation. This research will be conducted in collaboration with patients, healthcare providers, and communities to ensure it is feasible, relevant, and sustainable.

Mapping the Continuum of Respectful Experiences (CORE) in perinatal care among historically marginalised women and people in British Columbia

Evidence of disrespect and abuse during pregnancy and birth is increasing globally; however, little is known about the experiences of childbearing people in BC and high-quality data is needed, to address this serious issue. While it is essential to ensure a positive birthing experience regardless of the person’s background, research suggests that racialized and minority groups are more likely to report disrespectful treatment by care providers and are less likely to access high-quality care during pregnancy and birth.

In my study, I plan to analyze the pregnancy and birth stories from childbearing people, using several data sources and analysis approaches. Body mapping is a participatory method of data collection that will help to depict experiences of respect, disrespect and abuse. My goal is to create a Continuum of Respectful Experiences (CORE) model to describe complex, multi-layered experiences each birthing person may encounter during perinatal care. This model can be used as a tool to change patterns in care provision. It can teach care providers ways to reduce disrespect and abuse; enable person-centered decision making and understand the needs of people with different identities.

Structural exploration of locked nucleic acids (LNAs) for incorporation into anticancer oligonucleotides

Antisense oligonucleotides (AON) are short lengths of RNA or DNA molecules which are used to change gene expression to treat diseases like cancer and Parkinson’s disease. Like DNA, AONs are made up of chains of nucleotide units, but to make them useful as drugs, these nucleotides have to be structurally changed. Locked nucleic acids (LNAs) are a very useful type of altered nucleotide unit, since they are not broken down as quickly in the body, and attach strongly to the gene they are targeting. The problem with LNAs is that they are very difficult to make, so it is hard for chemists to make a lot of different changes to the structure of LNAs in order to find the best one to use in AONs.
The Britton research team recently discovered a new way to make LNAs very quickly and easily, in large amounts, from simple compounds. Using this new technology, we want to make a large number of structurally unique LNAs and, test them to find the best ones to use in AONs for the treatment of cancer.

Understanding critical care nurses’ prioritization of patient care

Delirium is a complication of a critical care (CC) admission. Although usually reversible, it can lead to long-term impaired thinking, poor mental health and increased mortality. Upwards of 80% of people admitted to CC will experience delirium. Research has been done to understand delirium and to prevent it. Factors that are known to help prevent delirium include a day-night routine, encouraging movement, and reducing sedating medications. CC nurses have control over many of these factors, but implementing strategies to prevent delirium remains sub-optimal. The lack of information about how CC nurses prioritize care to prevent delirium in the busy healthcare system leaves limited guidance for making change. This study aims to examine how CC nurses prioritize delirium-related patient care and to identify challenges and opportunities for change. The research will use surveys and interviews to gather data. This research is important for identifying gaps and opportunities to implement delirium prevention strategies needed to improve patient outcomes. The findings will allow CC teams to create a system to support a change in practice to improve the care and outcomes of patients.

Comprehensive dissection of tumor evolution in pediatric acute myeloid leukemia using single cell methylation sequencing

Pediatric acute myeloid leukemia (pAML) is a common type of cancer in children and is diagnosed in roughly 40 Canadian children each year. Although 90% of all children respond well to the initial treatment the cancer comes back for 20% of the children while being resistant to treatment, leading to a poor outcome. Current studies of treatment resistant cancers are not able to detect rare but important cells that form the cancer, which may be especially important in how treatment resistance occurs. Fortunately, new technologies allow for measurements from each of the thousands of individual cancer cells that form the tumor allowing us to detect rare cancer cells, including those that may result in treatment resistant disease. For the first time, we aim to use these technologies to focus on chemical properties of the DNA that influence how the DNA is interpreted, or read, by the cell. By studying patterns of these chemical properties in rare cancer cells and also normal cells we aim to learn if, and how, these patterns contribute to the phenomenon of treatment resistance in pediatric AML. With this knowledge, our ultimate goal is to prevent the formation of treatment resistant disease in this vulnerable population of patients.

Defining the landscape of genetic variation underlying rare human disease using nanopore long-read sequencing

Collectively, rare diseases affect millions of people worldwide. Understanding the molecular cause of rare disease has important implications for clinical management. However, although most rare diseases are suspected to be genetic in origin, the causal genes are not known in a majority of affected families. This study will use emerging technologies to better understand the molecular basis of rare genetic diseases. Long-read genome sequencing, a recent genetic testing technology, will help us to identify rare and complex genetic changes in individuals suspected to have harmful genetic variation. These findings will allow us to study how specific genes lead to congenital disorders and adult-onset cancer predisposition syndromes, genetic syndromes that increase the risk of developing specific types of cancers. This research will improve our understanding of normal and disease-causing genetic variation and help establish a foundation for the broader application of new technologies in the clinic.

Evaluation of SMPD3 as a quarterback for extracellular vesicle-mediated metastasis in oral carcinoma

Mouth cancer remains an under-studied and significant global cancer killer; dismal survival rates (~50% over 5 years) have not changed in decades. Potential spread to neck lymph nodes (metastasis) is the single most important prognostic factor but clinical assessment has not been very accurate. This results in insufficient surgery or over-treatment for many patients. A better understanding of mouth cancer and its way to spread is needed to improve treatment for the patients.
The SMPD3 gene is frequently dysregulated in mouth cancer it has been linked to metastasis. SMPD3 expression can impact microRNA (miRNA: small non-coding RNA molecules that regulates gene expression) cargo within extracellular vesicles (EVs). Many of these miRNAs have been linked to tumor invasion and metastasis. I hypothesize that mouth cancer cells that exhibit decreased SMPD3 expression plays a role in lymph node metastasis via specific miRNA EV content and that SMPD3 expression can be used as a biological marker for lymph node spread in mouth cancer.
We hope this project will lead to novel tools to identify the patients at highest risk for lymph node involvement, ultimately increasing survival rate and quality of life for mouth cancer patients.

Examination of Long QT Syndrome causing variants in induced pluripotent stem cell-derived cardiomyocytes to evaluate novel therapeutic treatments

The rhythmic beating of the heart requires coordinated electrical activity that causes the heart to contract and relax. The electrical activity is controlled by proteins in the membranes of heart cells that form ion channels. Failure of channels to work properly is associated with abnormal heart rhythm, heart attack and sudden death. Long QT Syndrome (LQTS) is a condition that affects 1:2000 people and often results from inherited mutations in one of the heart channels. However, determining whether a mutation will cause the individual serious heart problems is still a major challenge. By using cutting edge technology, like induced pluripotent stem cells and CRISPR, we can recreate patient mutations in cells in the lab and turn them into beating heart cells. Specific techniques can be used to look at individual heart cells, as well as heart cells in a layer that beat together. The properties of the cells can be measured so that the effects of the mutations can be understood, and so that newer specific drugs can be tested to see if they are effective against different mutation types. The results from this research will help inform clinicians on how to better help patients with LQTS and potentially identify new, better treatments.

Effect of age-related spinal degeneration on older adult spinal cord injuries

Spinal cord injuries (SCIs) are becoming more prevalent in older adults, and the number of older adults is rapidly increasing. This is a challenge for healthcare professionals because the existing health issues and poor health of older adults may limit invasive surgical treatments. The most common form of SCI seen in older adults is caused by the neck extending beyond its typical range, damaging the spinal cord in a pattern that is different pattern than what is seen in younger adults. It is known that the risk of spinal cord injury and observed tissue damage is worsened by age-related degeneration in the spine; however, there is limited understanding of how these degenerative changes alter tissue damage caused by an SCI. The proposed study will consist of three objectives: (1) to measure the type and amount of degeneration typically found in older adults, (2) to simulate the spinal cord injury and use it to predict how tissue will be damaged (3) to predict how the tissue damage changes when the model includes spinal degeneration.