Transcutaneous spinal cord stimulation for treating neurogenic bladder dysfunction following spinal cord injury

As much as 80 percent of people with a spinal cord injury (SCI) develop urinary bladder problems. Recovery of bladder function is consistently rated as a top treatment priority for people with SCI. Left unmanaged, bladder dysfunction can result in frequent urine leakage or unwanted urine retention that often cause kidney or urinary tract infections which drastically reduce overall quality of life. Despite the prevalence of this issue, treatment for restoring bladder function remains under-emphasized in SCI research. Of even greater concern are consequences associated with rapid, and often life-threatening, increases in blood pressure triggered by bladder care. Electrical spinal cord stimulation via surgically implanted electrodes is a potential treatment option that has been shown to promote functional recovery after SCI by modulating silent spinal circuits. However, the surgical implantation of electrodes and the stimulator is invasive, expensive and has inherent risks. We propose to improve bladder function and prevent associated blood pressure surges via non-invasive spinal cord stimulation using electrodes placed over the skin, thereby minimizing patient risk and obviating the need for invasive and expensive surgery.

Mechanisms underlying syncope: Defining the role of postural sway and gastric distension, and investigating the possibility of a cerebral trigger

Some people faint often, negatively impacting quality of life. Fainting occurs when the heart cannot pump enough blood to the brain. Standing still pulls blood into the lower body reducing its return to the heart. However, even when standing still, our body sways and these movements may prevent fainting by pushing blood to the heart. Water drinking might also help by stretching the stomach, raising blood pressure. Also, seeing blood/having blood drawn can cause fainting, suggesting the brain may trigger a faint, not the heart. We will examine: i) the role sway plays in fainting, ii) if fizzy water drinking wards off fainting, and iii) brain activity during emotional triggers. Using wearable sensors, we will compare heart rate, blood pressure, and sway patterns in the lab and in soldiers who faint on parade. We will test if drinking fizzy water increases blood pressure more than still water. We will also compare blood pressure, heart rate, and brain activity in fainters and non-fainters while participants watch a video of a blood draw to show the role of the brain in initiating faints. These studies will help us better understand fainting, relieving the healthcare burden and improving quality of life for people who faint.

Smart Discharges for Mom+Baby: Saving mother-newborn dyads by developing a predictive risk model to identify vulnerable dyads and guide delivery of post-discharge care

The risk of a mother or baby dying is highest in the first six weeks after birth. The World Health Organization (WHO) recommends regular follow-up visits for all mothers and their newborns. This is not always possible. In resource-constrained countries, a lack of money and nurses at hospitals and limited time and money at home often stops mothers from seeking care. In our study, we will build a score to identify mother-baby pairs that are most at risk of getting sick or dying in Uganda. The health of a mother impacts the health of their baby, and vice versa. Our risk score combines the risk of the mother and baby so that both can get care when they need it. A nurse can use this score to guide the number of follow-up visits recommended for the pair. In this way, mothers and babies at higher risk receive more visits. We will also talk to parents and nurses to determine what stops mothers and babies from receiving a follow-up visit. We will work with our Ugandan partners to remove these barriers so that improvements in care are long-lasting. In the future, we can use this approach to improve the health of mothers and babies in smaller, remote towns in BC, where specialized care for mothers and babies is not always readily available.

The role of the innate immune system in hypoxic ischemic brain injury post cardiac arrest

In Canada, more than 50,000 cardiac arrest (i.e. “heart attack”) patients simultaneously suffer from brain injury due to reduced brain blood flow and oxygen delivery. Primary brain injury occurs following the initial reduction in brain blood flow following cardiac arrest, and in some cases, secondary brain injury occurs after brain blood flow is restored to normal levels. However, the physiological mechanism(s) responsible for secondary brain injury following cardiac arrest remain unclear, and the data available in humans are very limited. We hypothesize that a key contributor to secondary brain injury following cardiac arrest is due to consequential activation of the human body’s innate immune system, which signals for excess brain inflammation and results in cellular damage. The proposed investigation, which will be conducted at Vancouver General Hospital, aims to measure key biological markers to quantify brain inflammation in post cardiac arrest patients. The findings from this study will improve our overall understanding of the mechanism(s) that contribute to brain injury characterized by reductions in blood flow and will potentially identify potential therapeutic targets and improve quality of life in these patients.

Dissecting heterogeneity in COPD: A functional imaging-guided-omics study

Chronic obstructive pulmonary disease (COPD) is a common lung condition with no known cure. Understanding lung abnormalities in COPD is critical to develop new treatments. However, lung abnormalities in COPD are ‘patchy’, and test samples (e.g. biopsies) used for laboratory studies may not be from the most diseased areas. We will use advanced lung imaging techniques (magnetic resonance imaging (MRI) and computed tomography (CT)) to identify ‘high-disease’ areas in the lungs of volunteers with COPD, and take samples from these areas using a camera inside the lungs (bronchoscopy). We will take samples before and after treatment with a common antibiotic medication (azithromycin) and test for changes in lung genes. Our approach may ultimately help develop new treatments for the 384 million people worldwide who suffer from COPD.

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.

In vitro diagnostics for frontotemporal dementia

Frontotemporal dementia (FTD) is a group of devastating brain diseases associated with progressive decline in behavior, language, and movement. FTD is the second most common form of dementia in those under 65 years of age. In the early stages of diseases when symptoms are very mild, FTD can be difficult to identify as its symptoms are similar to other neurological disorders like Alzheimer’s disease. Therefore, a reliable biofluid test is needed to help with early and accurate diagnosis of FTD. In this project, I will use state-of-the-art analytical techniques to develop a diagnostic test that can identify individuals with FTD. I will examine how the test performs in individuals with FTD compared to other diseases that have similar symptoms to FTD. This project will result in the creation of new diagnostic tests for the early detection of FTD. Early and accurate diagnosis of dementia is critical to ensure efficient access to medical care and social programs and will help researchers in developing new treatments for FTD.

The relationship between the cortico-reticulospinal tract and motor function in stroke survivors

Stroke is a leading cause of long-term disability in Canada that causes movement impairments on one side of the body. In cases of severe movement impairment, there is often extensive damage to the primary descending motor pathway in the brain originating from the opposite side of the body. When this pathway is damaged, secondary motor pathways are altered which may support recovery in these individuals. Several of these secondary motor pathways originate from the same side of the brain as the impaired limb and are therefore undamaged in cases of stroke. My research aims to comprehensively investigate the role of the secondary motor pathways in motor function with chronic stroke survivors that have severe movement impairments. This research will use a combination of state-of-the-art brain stimulation and brain imaging techniques to gain novel insight into the relationship between the secondary motor pathways and the control of voluntary movement. My research will provide valuable insight into the role of the alternative motor pathways. In turn this information can be used in clinical practice to implement rehabilitation strategies that lead to better recovery and improved quality of life in individuals with severe strokes.

Engagement in opioid agonist therapy and risk for repeat overdose in people living with and without HIV who experienced a nonfatal opioid overdose: Providing insight to improve clinical care

The ongoing drug toxicity and overdose (OD) crisis has ruined the lives of many people in British Columbia (BC). Opioid agonist therapy (OAT) reduces the risk for an OD, but not everyone who needs OAT has access to and is taking OAT. People living with HIV (PLWH) are disproportionately affected by the OD crisis and may be less likely to have access to OAT. This project aims to contribute to a strategy to connect people who visit an emergency department (ED) or a hospital due to a nonfatal opioid OD (NFOOD) with primary care and OAT. I will use routinely collected health data on all PLWH and a 10 percent random sample of the general population in BC, between 1992 and 2020. I will investigate — of everyone who visited an ED or a hospital after a NFOOD — who is most at risk of 1) not being connected to primary care and OAT, and 2) a repeated OD. I will compare people living with and without HIV. I also will have conversations with professionals from various backgrounds and individuals with lived and living experience. Through these, I hope to learn more about barriers to care. Based on what I learned, I will formulate recommendations on how to help people that experienced a NFOOD connect with care that best suits their needs, including OAT.

The association of genetic risk factors with morphology and outcomes in interstitial lung disease

Interstitial lung disease (ILD) is a diverse group of illnesses with a variety of causes. The current approach to diagnosing ILD depends on the specific patterns observed on imaging studies (CT scan) and lung biopsy. There is increasing evidence that an individual’s genetics play a complex and important role in determining disease behaviour across different ILD subtypes. This study will examine whether common genetic risk factors predispose patients to different forms of ILD, influence treatment response, and predict prognosis. Investigating these genetic risk factors will improve our understanding of the biology that drives ILD and will help to develop a better system for ILD classification and diagnosis.