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.
Program: Trainee
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.
Evaluating the impact of pharmaceutical interventions to reduce overdose among people with criminal justice system involvement in British Columbia
People with criminal justice system involvement (i.e. who have been to prison for a criminal offence) are more likely to use drugs like heroin and methamphetamine compared to the general population. People who use drugs also are at higher risk of negative outcomes like overdose and more rapid or frequent return to prison. Efforts to address overdose, both in prisons and in the community, have been focused on providing treatment for people who use opioids (e.g. heroin, fentanyl). This alone may not be sufficient to reduce overdose risk, particularly among people who use other substances (e.g. cocaine, alcohol) in addition to opioids. In March 2020, in the context of COVID-19, the British Columbia (BC) Ministry of Health provided new Risk Mitigation Guidance (RMG) for doctors, permitting them to prescribe opioids, stimulants, benzodiazepines, and alcohol withdrawal management medications to people at risk of overdose. In this study, I will evaluate whether the RMG has reduced overdose and return to prison among people with criminal justice system involvement in BC. This study will highlight gaps in substance use services in BC, and will inform evidence-based services that can help to reduce overdose in prison and community.
Developing a method to implement patient-centered social robotics for pediatric mental health within the BC healthcare system
Could a small, interactive robotic character or pet be used in a hospital to help support children’s mental health? While children are often interested in interacting with robots, the design of these devices rarely incorporates patients and families’ needs and values. For social robots to be ethically implemented in healthcare, they must be developed according to patients’ priorities, supported by high-quality scientific evidence, and well-suited to implementation by real-world healthcare providers.
To address this, I will hold co-creation workshops with children and families with a lived experience of a childhood mental health disorder to identify goals for and barriers to social robot interventions. I will also interview key health services stakeholders who would be most involved in using a robot in the hospital — nurses, CLSs, and others — about advantages, concerns, and obstacles to deploying a social robot for pediatric mental health, as well as proposing a Health Technology Assessment.
Taken together, these research findings will facilitate the development of practice and policy for the evidence-based, patient-centred deployment of social robots to improve the wellbeing of BC children experiencing mental health challenges.
The influence of podocalyxin expression on immune response to ovarian cancer and the efficacy of an antibody-drug conjugate in immunotherapy
Despite significant advances in the treatment of many cancers, ovarian cancer still claims hundreds of lives in Canada every year. A molecule called podocalyxin is “switched on” by a high percentage of tumors from various cancer types including ovarian cancer and its expression is associated with poor prognosis. Since the immune system has a key influence in the control of tumor growth, one of my objectives will be to study how podocalyxin influences the immune response against tumors.
In addition, Dr. McNagny’s team recently developed an antibody, called PODO447, which recognizes an exquisitely tumor-specific form of podocalyxin. Accordingly, my second objective will be to explore the use of this antibody as a method to either attract immune cells to cancer cells and kill them or as a tool to deliver toxins and chemotherapeutic agents specifically to tumor cells while sparing normal tissue. Preliminary experiments in animal models already are suggesting the efficacy of the latter approach. In conclusion, the results obtained in this project will allow us to take one more step toward the objective of ultimately treating ovarian cancer patients with the podocalyxin targeting therapies.
Evaluating the safety, efficacy, effectiveness, and immunogenicity of meningococcal vaccines across the age spectrum
Meningitis is a serious inflammation of the lining surrounding the brain and spinal cord, caused by viral or bacterial infections. One in ten people who develop meningitis will die, and 20% will experience serious, lifelong consequences, such as hearing loss or brain damage. The World Health Organization (WHO) has called for full prevention and control of this disease by 2030. Our team is collaborating with the WHO to develop evidence-based immunization strategies for this initiative. My research project will pool data from all previous vaccine studies on meningococcal group B (MenB), to assess the safety and protective effect of different MenB vaccines. Our goal is to use that data to answer questions such as, “How safe current meningococcal group B vaccines are?”; “How long they can protect us from getting the disease?”, and “How many doses are needed and on which schedule?”. Findings from this research will guide WHO strategies on dosing and timing of vaccines, to eradicate meningitis by 2030.
An iKT, interpretivist, feminist, multi-method study examining the experience of, and models of treatment for, acute postpartum mental illness
Postpartum depression is common, affecting 10-15% of women, and increases risk for suicide. Postpartum psychosis is rarer (approximately 1/1000 women), but is a psychiatric emergency. Women with postpartum psychosis or severe postpartum depression need care in hospital to protect their health, and the health of their families. Currently in Canada, these hospital stays separate women from their babies, which can be traumatic for mother and baby. In other countries, Mother-Baby Psychiatric Units (MBUs) admit both mother and infant for care. This study will investigate whether MBUs are suitable for Canada, or whether another model of care would be better for Canadian families. To do this, we will conduct three sub-studies. Sub-study 1 will amplify women’s stories of the experience of a hospital stay for postpartum mental illness in Canada. Sub-study 2 will describe the frequency and predictors of hospitalization for postpartum mental illness. Sub-study 3 will provide a rich picture of the MBU model of care through a case study of five international MBUs. By understanding how to best meet the needs of women and families living with serious postpartum mental illness, we aim to improve mental health outcomes across generations.
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.