Ophthalmic imaging plays a crucial role in the evaluation, follow-up, and treatment decision-making in ocular oncology. This critical role is even more prominent when dealing with the early-stage choroidal melanoma or amelanotic tumor patients, in which diagnostic uncertainty is especially prevalent. This is due to the significant overlap in the clinical and imaging findings of benign and malignant choroidal tumors. Current imaging modalities are not helpful in reliably differentiating the malignant features in suspicious choroidal lesions and often require long-term serial follow-up that places a significant burden on patients and providers. Recent studies have shown that melanin alternation in the choroid is correlated to the malignancy and metastasis potential in choroidal tumor patients. The main goal of my research is to develop a novel high-resolution, molecular-specific clinical ophthalmic imaging system to visualize and quantify the melanin contents in choroidal tumor. This research outcome will provide important diagnostic clues in the evaluation of choroidal tumors, facilitating early non-invasive identification of high-risk features of malignancy.
Research Location: Vancouver General Hospital
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.
Multimodal characterization and classification of bio-signals to predict cardiac arrest
Sudden cardiac arrest (SCA), due to abrupt disruption of cardiac function, is a major health problem globally. SCA can happen to anyone at any age who may or may not have been diagnosed with heart disease. SCA has a poor survival rate of about 10 percent, with an estimated 35,000 deaths in Canada annually. With an increasing rate of cases (16 percent from 2017 to 2020), SCA remains a major public health issue in British Columbia. The most effective strategy to improve survival is to achieve rapid SCA recognition, given that for every minute without cardiopulmonary resuscitation (CPR) survival rates drop by 10 percent. Wearable devices may play a major role in decreasing SCA mortality, providing real-time cardiac information for early SCA detection. My aim is to develop a wearable SCA device with embedded sensors, and use their real-time physiological data combined with artificial intelligence algorithms, to make an accurate SCA detection system. This SCA detection system will be designed to identify SCA and alert Emergency Medical Services with the individual’s location (via GPS), enabling them to provide life-saving interventions in a timely manner.
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.
End of award update: June 2021
Most exciting outputs:
The home health monitoring (HHM) research is now being applied in practice, within the fabric of the health system. What we have learned is being applied and has been used in policy making. Methods and an evaluation framework have informed not only this project, but the evidence used in the real world.
While results from the full randomized controlled trial are forthcoming, the findings from our feasibility study showed signals of overall positive impact. This included reduction of emergency department revisits, hospital readmissions, and hospital length of stay. Results also showed an improvement in quality of life and self-efficacy. Further, feedback from patient participants indicate the HHM service was well received and helped participants feel safer and more supported at home after discharge from the hospital.
The TEC4Home Heart Failure study also resulted in the expansion of the concept to new conditions (like hypertension) and new technologies (such as an in-home medication dispenser). These new projects will continue to collect and build a body of evidence to best inform how digital health can help support the transition of care from hospital to home for a variety of patient populations in BC.
Impact so far
The findings from this project have been used to inform the ongoing implementation of home health monitoring in BC. It is our goal to continue to add to this evidence and see the application of these findings in the health system.
Potential future influence
At a provincial level, as noted above, the PI, K. Ho, is a member of the Digital Health Committee in BC. This involvement allows for project findings to be applied in alignment with existing policies and to inform emerging policies.
Further, the PI, K. Ho, is also a member of multiple national committees, such as the Canadian Virtual Care Task Force (focused on digital health implementation and education); the National Research Council (focused on medical device research with influence on national digital health research in practice); and the Health Canada scientific advisory committee (focused on the regulation and support of industry in digital health). All of these memberships provide opportunities for health policy influence.
Next steps
Over the course of the next year (to Mar 2022), we will be completing the final analysis of our TEC4Home Heart Failure randomized controlled trial. The results will be shared back to our various project committees and partners, including all of the patient participants. We will also seek more dissemination opportunities, such as publication in a high impact journal and presentation at conference(s).
In addition, as previously mentioned, with recently acquired funding, we are applying the TEC4Home concept to new conditions (hypertension) and new areas of impact (medication adherence). We are also incorporating the use of data analytics to deepen our understanding and the application of home health monitoring. This expansion of TEC4Home will continue to develop the evidence base of the use of technology to support patients safely at home, as they transition from acute to community care.
Useful Links
Digital Emergency Medicine (DigEM) website: TEC4Home Heart Failure | Digital Emergency Medicine (ubc.ca)
https://digem.med.ubc.ca/projects/tec4home-telehealth-for-emergency-community-continuity-of-care-connectivity-via-home-telemonitoring/
Feasibility Study publication: Testing the Feasibility of Sensor-Based Home Health Monitoring (TEC4Home) to Support the Convalescence of Patients With Heart Failure: Pre-Post Study – PubMed (nih.gov) https://pubmed.ncbi.nlm.nih.gov/34081015/
Trial Protocol publication: Supporting Heart Failure Patient Transitions From Acute to Community Care With Home Telemonitoring Technology: A Protocol for a Provincial Randomized Controlled Trial (TEC4Home) – PubMed (nih.gov)
https://pubmed.ncbi.nlm.nih.gov/27977002/
VCH news article about launch of trial: TEC4Home moves forward to clinical trials – Vancouver Coastal Health (vch.ca)
http://www.vch.ca/about-us/news/news-releases/tec4home-moves-forward-to-clinical-trials
Blog post by HeartLife: TEC4Home: Improving self-care management for heart failure patients – HeartLife Foundation
https://heartlife.ca/2019-3-1-tec4home-improving-self-care-management-for-heart-failure-patients/