Delineating the pathophysiology of hypoxic ischemic brain injury after cardiac arrest to identify therapeutic targets

The main determinant of patient outcome following revival from cardiac arrest (heart stops pumping blood and oxygen to the body) is the brain injury that occurs in the days after hospital admission. This injury, termed hypoxic ischemic brain injury, partly arises from a lack of oxygen delivery to the brain after resuscitation. The cornerstone of post-cardiac arrest management has involved increasing the delivery of oxygen to the brain to facilitate recovery.  This logic assumes that the transport of oxygen from the blood system into the brain tissue is normal after cardiac arrest. I have recently demonstrated that this assumption is not true and in fact, in a large proportion of post-cardiac arrest patients demonstrate an inability to unload oxygen into the brain from the blood vessels. The mechanisms explaining this observation are unclear and not accounted by tests including CT and MRI scans. Therefore, another approach is required.

My project involves using a series of novel blood tests that arise from structures in the brain that are responsible for oxygen transfer. Identifying the precise structures that inhibit oxygen delivery into the brain will lead to further research aimed at identifying therapeutic targets.

eSense: an online psychological intervention for women’s health

Sexual dysfunction affects up to 1/3 of women across ages, cultures, and social conditions. The World Health Organization recognizes sexual health as a fundamental part of general health and quality of life. Our research shows that face-to-face cognitive behavioural therapy (CBT) and mindfulness (MBT) are effective for treating women’s sexual concerns. Yet these treatments reach only a small segment of women, and are accessible primarily to women who have the means to commute to large centres. Access barriers disproportionately affect women of colour, women of Indigenous communities, and women living in rural and remote regions.

We propose that online treatment programs are an effective strategy to solve this problem. In this project, we will evaluate our online program for women’s sexual dysfunction, named eSense, which contains separate modules of CBT and MBT therapy skills. We will then make eSense available to patients seeking healthcare in two Vancouver sexual health clinics and collect user feedback to further improve the program. The longer term goal is to commercialize eSense as a tool to deliver evidence-based skills for improving sexual health in women and improve their quality of life.

Sexual pain in endometriosis: Role of somatic mutations

Endometriosis is a common condition, affecting 1 in 10 women of reproductive age, or approximately one million women in Canada. Endometriosis occurs when tissue from inside the womb grows outside of the womb, such as in different areas of the pelvis. Half of women with endometriosis experience sexual pain, which is felt as pelvic pain with deep penetration during sexual activity. 

Sexual pain in endometriosis can occur when the endometriosis cells show invasive qualities. We recently identified non-inherited gene mutations in this type of invasive endometriosis. 

Our team has established a registry of endometriosis patients along with surgical samples from these patients. I will validate the role of gene mutations in endometriosis sexual pain, in particular whether these mutations are associated with invasion of endometriosis, and also with increased nerve growth around endometriosis. 

In the future, gene mutation testing could be incorporated into clinical care for endometriosis to identify subgroups and promote more individualized care. These mutations could also be potential novel treatment targets for this common condition in women.

Cerebral Oximetry to assess CErebral autoregulation in Hypoxemic Ischemic Brain Injury (COnCEpT – HIBI)

There are 40,000 patients who suffer a cardiac arrest in Canada each year. When the heart stops beating from a cardiac arrest, blood flow to the brain stops which can lead to large strokes, called ischemic brain injury. Only a small percentage of people who develop ischemic brain injury survive with normal brain function.  

The overall goal of this research is to improve the neurologic outcomes of critically ill patients who have suffered a severe brain injury after cardiac arrest by determining how to personalize blood pressure targets for individual patients to ensure adequate cerebral blood flow (CBF). CBF in the first few millimetres of brain tissue can be measured non-invasively by near-infrared spectroscopy (NIRS), using sensors applied to the forehead. I have previously demonstrated that we can use the NIRS to determine the patient-specific blood pressure, but it is unclear if maintaining this individualized blood pressure leads to better outcomes.

To address this gap, my Heart & Stroke Foundation funded study will enroll 60 patients in 3 intensive care units across Canada following cardiac arrest. The objective is to determine the association between the amount of time spent at the patients individualized blood pressure threshold, and neurologic outcomes at 6-months. The results of this study will be used to design a large interventional study of individualized blood pressure management and neurologic outcomes.

SECRET: Study of rivaroxaban for CeREbral venous Thrombosis

Cerebral venous thrombosis (CVT) is a rare type of stroke that can cause headaches, vision loss, weakness, seizures and coma. It is most common in young women and causes 1/3 of strokes that occur around pregnancy. Among those affected, up to 15% are left dead or disabled, 25% cannot return to work, and over half have lasting issues with energy, thinking or mood. 

As a rare disease, CVT is hard to study in large trials, and treatment decisions are based on clinician opinion. CVT is treated with strong blood thinners, but it is not clear which blood thinner is best or how long people should be treated. We are conducting a national study to determine the best way to treat CVT.

Collaborating with 18 other hospitals we will recruit patients from across the country. People living outside of major cities can participate in the study over video-conference and we will also hold forums to consult with patients and family members about lasting symptoms that affect their quality of life. 

Our aim is to improve treatments for CVT, and better understand its long-term effects. We also want to continue to expand our video-conference network so that people with health issues will be able to access research treatments, regardless of where they live. 

Health related quality of life following road trauma: An emergency department inception cohort study

Each year in Canada, road trauma causes over 2,000 deaths and 10,000 serious injuries. Disability after an injury is a major public health concern, but the long term health outcome after road trauma is poorly investigated and based mostly on older research that does not reflect modern vehicle safety features or modern medical treatment. In addition, there is almost no research that helps health care providers know which patients are most likely to have a bad outcome following a crash, making it difficult to provide them with the care they require. For policy makers, it is important to know the health care costs and lost productivity that results from road trauma, but this information has not been studied. My study will provide this missing information.

My team will interview patients who visit an emergency department after a traffic crash, including pedestrians, cyclists, and motorists. We will ask about their general health before the crash, the injuries they had from the crash, and other details of the crash. Repeat interviews at 2, 4, 6, and 12 months will ask about problems they had since the crash, including pain, ability to go about their usual activities, and return to work. We will also ask about the medical care they required after the crash.

This study will help doctors and nurses know how quickly people recover from their injuries after a crash and which patients are likely to have long term health problems. It will also describe the medical treatment that these patients require and how much work they miss. This information will give a better estimate of the true cost of road trauma, and may help policy makers decide how much funding to devote to crash prevention programs or to treatment programs for crash victims.

TEC4Home: Telehealth for emergency-community continuity of care connectivity via home monitoring

Patients with long term medical conditions like heart failure or chronic lung diseases typically get admitted to and discharged from hospitals frequently because their conditions fluctuate. For example, one out of four patients older than 65 with heart failure often needs to return to hospital within one month of a previous emergency room or hospital stay. Today, using electronic monitors, patients can measure their own blood pressure, weight, and blood oxygen from home, and send their measurements to doctors or nurses so they can supervise the patient's state of health. We are testing this home health monitoring approach to see if it can help patients with heart failure or chronic lung diseases stay healthy and safe at home.

In our research program called TEC4Home, we hope to show that home monitoring: 1) helps patients to manage their illnesses better themselves because they know their own bodies best, and 2) allows nurses and doctors to follow patients closely without needing to visit them. We expect to show that these patients will stay well and not need to revisit emergency departments, thereby helping hospitals to save money or save the beds for sicker patients.

We will first invite 90 patients with heart failure from Vancouver General and St. Paul's Hospitals to test the home monitoring approach after they go home. Findings will allow us to make improvements before we expand to enroll 900 patients in 30 hospitals in BC in a formal clinical study.

Provided TEC4Home is found to help patients and decrease hospital costs, we will expand this service to be offered to other patients with heart failure across BC. We will invite companies that make monitoring equipment to develop newer and better versions, and use our experimental approach to test these devices to ensure they are safe and useful. We will also test TEC4Home with patients with chronic lung diseases to expand TEC4Home to serve patients with more than one type of long term disease.

We will work closely with doctors, nurses, patients and families, hospital managers, government leaders, technology companies, and health researchers. Patients will not only test the approach, but will also be involved in planning and carrying out the research. We will share findings with governments and health organizations so that home health monitoring, if proven effective, will become a routine part of treating patients. We will present at medical conferences and publish to share learnings beyond BC.

The Impact of a Resident Work Schedule Change on Patient Safety

After graduation from medical school, physician education continues in a residency program in the individual's chosen area of specialty (e.g., Surgery, Internal Medicine). Residency programs have grueling schedules with frequent on-call shifts. These shifts are at least 24 hours in length, starting from the morning of one day and extending to the next day. In teaching hospitals, residents often provide first line care and make important decisions independent of direct supervision. Their clinical performance is thus an important determinant of patient safety. Some have argued that shift length should be reduced to a more reasonable amount (e.g. <16 continuous hours) to reduce fatigue and medical errors, and to improve safety.

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Development of a screening strategy for community-based adverse drug related events in the emergency department

Adverse Drug Related Events (ADREs) are the most common type of preventable non-surgical adverse event related to medical care, and represent a leading cause of death. Each year, in BC alone, Emergency Departments treat an estimated 130,000 patients for ADREs, most of which are caused by medications prescribed in community settings. Unfortunately, community-based programs aimed at detecting and reducing drug-related problems have not led to a significant decline in morbidity, mortality or health services utilization. Emergency Department practitioners are well situated to play a pivotal role in the timely recognition and treatment of community-based ADREs. Unfortunately, Emergency Physicians currently detect only 50% of ADREs, missing opportunities to intervene.

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Examining segmental sensory function and recovery in individuals with spinal cord injury using dermatomal somatosensory evoked potentials

More than 30,000 Canadians live with spinal cord injury (SCI). SCI often leads to devastating neurological deficits that markedly reduce quality of life and life expectancy. During the first year of SCI, individuals typically recover some sensory function. Sensory testing, an important component of early diagnosis and prognosis, is currently done with light touch and pin prick sensation tests. Though this method is valuable for quickly assessing sensory function, it has limitations: it is difficult to obtain reliable results from uncooperative or unconscious individuals, it does not provide a quantifiable measure of sensation, and does not identify minor changes in sensory function. In undamaged sensory pathways, electrical impulses are rapidly conducted along mixed nerves to the spinal cord, where they ascend in sensory pathways to the brain. Following SCI, the spinal cord is typically compressed and damaged but not completely severed, meaning an electrical signal can still be recorded from the brain. However, this signal is expected to be delayed and to undergo distinct changes in the path it follows to the brain. John Kramer is examining spinal cord conductivity during recovery, applying methods currently used in clinical neurology, but new to SCI practice. He is assessing conductivity at each level of the spine by stimulating specific areas of the skin’s surface with electrical current, and recording the activity with scalp electrodes. To describe the contribution of sensory function at each level to sensory recovery, he will conduct these tests multiple times over the first year of SCI. Kramer’s investigation will provide important information concerning sensory recovery following SCI. The results from this study will have implications for delivery of care for individuals with SCI, and will prove beneficial for determining the efficacy for future SCI interventional therapies