Novel infection resistant coating for indwelling urinary devices

Urinary catheters are polymer tubes inserted into the bladder to drain urine. Over 25% of patients in hospital are fitted with a catheter during their stay. These tubes are a major cause of infection in hospitalized patients and result in longer hospital stays with skyrocketing health care costs and may result in death. In fact, infections acquired in hospitals are the fourth leading cause of death in hospitalized patients. 

Currently, antibiotics are our only method of attempting to deal with these infections, but they do not work well. Bacteria form large communities, known as biofilms, on the surface of the catheter, which can render antibiotics ineffective. Additionally, bacteria have developed ways to inactivate antibiotics and become resistant, making them difficult to kill.

Dr. Lange has developed a breakthrough technology based on a special coating for catheters. The coating is inspired by nature—it’s very similar to what marine mussels use to attach to surfaces—and prevents bacteria from attaching to the catheter surface without killing the bacteria, which would induce resistance. Instead, by preventing bacteria from attaching to surfaces, we leave them exposed for our immune system to kill.

Dr. Lange’s preliminary studies have shown that this new coating prevents the attachment of different types of bacteria to the catheter surface in test tubes and in a realistic urinary environment in animal models. The coating doesn’t break down over time and can be used to cover many different types of materials. 

The next steps for this technology will be producing catheters with this coating, including testing its effectiveness over long periods of time in larger animals, ensuring it cannot be rubbed off, and that it stays active under conditions it would face in medical environments. Although this project is specifically looking at catheter infections, the data that Dr. Lange will generate will provide a general method for preventing infections associated with other medical devices, another major problem in hospitals.

Custom platform for preoperative planning of complex head and neck reconstruction

Advanced head and neck cancers involving facial bone often require aggressive removal of diseased bone. Reconstruction of the bone is typically done by cutting and reshaping patient donor bone. This process involves is complex, since the accuracy of the reconstruction significantly impacts cosmetic and functional outcomes. Doing this during surgery is challenging, time-consuming and can be improved with better planning before surgery. 

One method of pre-operative planning is to use patient imaging data to perform virtual reconstructions and design 3-D printed cutting guides for use during surgery. Currently, the only way to obtain such guides is through a third party and costs between $2000 – $6000 per case. However, this process has a significant turnaround time and surgeons have limited input on how the actual guides are designed. 

My group has developed a software that makes the pre-operative process fast, simple and effective. We currently have the capacity to plan mandible (lower jaw) reconstructions with the fibula (lower leg) and are now validating the process through a clinical trial. We hope to extend the software capability to other surgeries and conduct research to generate supporting evidence.

Smart Text Analytic Tools (STAT) for analysis of patient-centred communications to strengthen health systems in BC

Healthcare stakeholders, including health authorities, facilities, pharmaceutical companies and insurers are increasingly acknowledging the importance of big data to enhance understanding of health behaviours and health systems. Existing analytic tools available to navigate the volume of diverse data types at a frequency that can match the speed at which data is generated are in early stages of development, and often lack validation due to limited access to health data. The ability of healthcare stakeholders to make sense of this valuable data is restricted by a lack of capacity and user-friendly analytic tools. 

Dr. Lester leads the UBC mobile health (mHealth) research team, which has been developing a set of smart-text-analytic-tools (STAT) to analyze patient and care provider communication data in the form of open natural language text. The WelTel digital health platform was created by Dr. Lester and has been tested in a diversity of geographic (Kenya, Canada, USA, South Africa) and health settings (HIV, TB, Asthma, maternal and child health) since 2005. The result of twelve years of mHealth research is a dataset consisting of hundreds of thousands of text messages sent by patients and providers. Topics of discussion include advice related to medication side effects, information requests, and the need for access to psychosocial and logistical support services. This data has the potential to identify outpatient self-reported priorities over time, informing patient-centered improvements in health system responsiveness and preparedness. 

The UBC mHealth research group will further develop STAT into a minimum viable product  that can analyze a variety of open natural language text data using natural language processing. This tool will allow both public health systems and private enterprise to streamline approaches to analyzing large volumes of text-based data.

Development of a novel organ preservation solution in transplantation

There is a need to improve donor organ preservation strategies to meet donor organ requirements for transplantation. Strategies such as cold flushing and organ preservation solutions are common practices to mitigate organ damage incurred during the transplant procurement, transport and implantation processes, but these solutions can be inadequate for marginal or extended criteria donors (ECD) that are being used in response to increased demand. New organ preservation solutions that are more effective in protecting donor organs, particularly from ECD, are required to fill this gap.

To address this unmet need, Dr. Du’s lab is developing new organ preservation solutions using a novel hyperbranced polyglycerol (HPG). Proof-of-principle  studies using cell cultures and rodent transplant models have shown that this HPG organ preservation solution performs better than conventional solutions in the cold preservation of organs and human cells. A patent application for the technology was granted in May 2015.

Dr. Du’s technology has garnered interest from top companies and key opinion leaders in the transplantation field. To sufficiently validate and de-risk the technology, enabling him to attract industrial interest, Dr. Du will compare the efficacy of HPG organ preservation solution with conventional solutions in donor kidney preservation with a non-human primate model. If the HPG solution performs adequately, it will lead to a clinical trial. 

The success of this technology could lead to a needed increase in the number of organ transplantations for British Columbians who need them.

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.

Implementing concussion return to activity guidelines in primary care

Throughout the history of medicine, patients who had a disease that was poorly understood were advised to rest. As scientists and doctors learned more, early mobilization and active therapies (e.g., exercise) gradually replaced rest as the conventional treatment for a variety of medical conditions, such as chronic fatigue, whiplash, stroke, low back pain, and cardiac arrest. We have now reached this same juncture for concussion care. The proposed project aims to figure out how to support doctors in implementing new science-informed return to activity guidelines for concussion.

By way of background, concussions (also known as mild traumatic brain injuries) are very common, affecting more than 20,000 people each year in British Columbia's lower mainland alone. Concussions have been historically treated with rest. An explosion of concussion research over the past decade has led to several important insights. One such insight is that resting for more than a few days does not speed up recovery, and in fact, may cause harm (for example, lead to social isolation and depression). There is also emerging evidence that exercise is an effective treatment. Guidelines for clinical care prepared by Canadian and international concussion experts now emphasize that patients should gradually return to activity (e.g., school, work, recreation) soon after injury, as tolerated. Nevertheless, rest remains the most common treatment prescribed by doctors. It is promoted in pamphlets and websites designed to educate patients about their injury.

The goal of the proposed research is to bridge the gap between concussion science and clinical care, and study how effective this knowledge translation effort is. We focus on family doctors because they are best positioned to counsel patients about returning to activity after concussion. We have assembled a package of knowledge translation strategies based on behaviour change theory, prior research on how to best implement new clinical care guidelines, and input from the kind of doctors and patients who could most benefit from this knowledge. The study plan involves learning about doctors' behaviour through an online survey tool each time they see a patient with a concussion, and measuring patient outcomes through telephone-based assessments. We will measure changes in how doctors manage concussions and whether those changes result in corresponding improvements in how quickly patients recover from a concussion.

Strategies to Promote Mobility and Physical Activity in Older Men in Assisted Living

Older men in assisted living spend up to 90 percent of their time in sedentary behavior. This lack of physical activity makes them more vulnerable to mobility-disability. Currently, 40 percent of Canadian men over the age of 75 already present some degree of mobility-disability. Mobility limitations lead to frailty, falls, and placement into higher levels of care. To promote mobility and physical activity in older men living in assisted living facilities, a better understanding of how they move is needed. This in turn helps assisted living facilities better customize programs that enhance their participation, and thus, improve their mobility.

To address the gaps, I will develop and evaluate strategies that promote mobility and physical activity (in older men who live in assisted living). More specifically, I will address the following two objectives:

  1. Examine how real-life measures from wearable sensors of the quality of movement (e.g. time required for transferring, gait speed) and quantity of movement (e.g. activity levels) associate with frailty and risk for falls in older men. I will use wearable sensors to measure mobility patterns during standard clinical tests and as residents go about their daily activities (e.g. walking, transferring, standing, seated, and lying).
  2. Examine how mobility and activity levels are influenced by a customized physical activity program and real-time feedback monitored by wearable sensors. I will conduct a 12-week randomized control trial of a customized physical activity intervention for older men in assisted living. Participants will be randomly assigned to either the program currently offered by a facility (control group) or to a physical activity program that is custom-designed based on the results under objective 1 (intervention group).

This project will be conducted in partnership with Fraser Health and the BC Care Providers Association. I hypothesize that participants in the intervention group will show greater improvement in measures of mobility, falls efficacy, and fall incidence. I will work with partners to refine my research objectives and disseminate results at the end of the trial. Findings will be shared through presentations, workshops and publications. By sharing best practices for mobility and physical activity promotion, I ultimately want to impact the older men who are in assisted living.

TEC4Home: Telehealth for Emergency-Community Continuity of Care Connectivity via Home telemonitoring

MSFHR is contributing matched funding for Dr. Kendall Ho’s research, one of 22 projects funded through the Canadian Institutes for Health Research (CIHR) eHealth Innovation Partnership Program (eHIPP). eHIPP was designed to address gaps in health care—including supporting seniors with complex care needs in their home—by stimulating collaborations between health researchers and Canadian innovative technology companies.The BC Ministry of Health and industry partner TELUS Health are also supporting Ho’s research. MSFHR is also funding the eHIPP research projects of Dr. Ellen Balka and Dr. Scott Lear. In 2017, Ho received a MSFHR Health Professional Investigator Award related to this project.

Continue reading “TEC4Home: Telehealth for Emergency-Community Continuity of Care Connectivity via Home telemonitoring”

Co-targeting Hsp27 and EGFR as a strategy to improve EGFR targeted therapies in EGFR dependent solid tumors

Epidermal Growth Factor Receptor (EGFR) is a key regulator of cell proliferation and a driver oncogene in several tumors. Many cancers have constitutively activated EGFR which leads to excessive signalling. Inhibition of EGFR using erlotinib or gefitinib significantly improves survival in patients with Non Small Cell Lung Cancer (NSCLC) while panitumumab and cetuximab are currently used in colorectal and head and neck cancer. Despite good initial responses to these drugs, the patients develop resistance and eventually die of recurrent disease. EGFR inhibitors induce stress responses that promote emergence of acquired resistance.

We identified Heat Shock protein 27 (Hsp27), a stress induced chaperone protein correlated to treatment resistance in several tumors, as a mediator of resistance to erlotinib in NSCLC. Hsp27 becomes phospho-activated after erlotinib and helps stabilize EGFR. We developed the Hsp27 antisense inhibitor OGX427 which can block the adaptive survival response and enhance the activity of erlotinib and other anti-cancer drugs and now in phase II clinical trials in lung, pancreas, bladder and prostate cancers. While the activity of OGX427 is promising, a more potent and orally active inhibitor may improve cancer control; however small molecule inhibitors are difficult to develop because of the complex structure of Hsp27.

Using a series of drug screening assays, we identified a new drug, VPC27, that functionally inhibits Hsp27 with a good tolerability profile in mice studies. The aims of this project are: a) to compare the activity of VPC27 and OGX427 on tumor proliferation/survival in different EGFR dependent solid cancers alone or in combination with EGFR inhibitors; b) to define the molecular mechanisms that link Hsp27 with resistance to EGFR inhibitors, focusing on kinases and phosphatases proteins that regulate the phosphorylation and dephosphorylation of Hsp27 and EGFR.

These studies aim to build upon two strategies that are revolutionizing the treatment landscape in cancer: the use of molecular-targeted agents inhibiting driver oncogenes and the inhibition of adaptive responses that support development of resistance. Co-targeting treatment-induced adaptive responses mediated by Hsp27 can sensitize cancer cells to EGFR inhibitors and improve the efficacy of these drugs. Moreover, understanding mechanisms by which Hsp27 regulates EGFR activity is important to identify new molecules that could be used as new targets in cancer therapy.

How is the motor learning capacity of a skilled walking task affected after an incomplete spinal cord injury?

Many people who have an incomplete spinal cord injury (iSCI) have the potential to improve their ability to walk. Current training strategies are limited in their ability to target skilled walking tasks (e.g. stairs and obstacles).

Sensory function can be affected after iSCI. We believe that this could influence success at re-learning these tasks, because previous studies show that impaired sensory feedback from the leg muscles can influence how the foot moves while walking.

The goal of this work is to investigate how well people with an iSCI can re-learn a new skilled walking task, and to evaluate the impact of impaired sensory function in the lower limbs on this process.

Our findings will shed light on how reduced sensory function affects people re-learning skilled walking tasks after iSCI.