The unprecedented investment in biomedical research during the past 50 years has resulted in many important advances in health care knowledge. However, the successful and timely integration of these advances into clinical practice remains a major challenge, especially in primary care and community settings. There is growing recognition that one of the obstacles to translating knowledge into clinical practice may be the knowledge itself, and how, where and by whom it was generated. Often, research knowledge is created in academic settings with little opportunity for involvement or input from primary care providers, community partners or patients. Dr. Janusz Kaczorowski aims to generate more high quality research evidence by end-users themselves, and under clinical conditions that closely resemble real life primary care and community settings. He believes that such an approach will help develop evidence that is more relevant to healthcare professionals working in these setting, which will speed up the knowledge transfer process. Building on his previous work across North America, Kaczorowski’s research focuses on the development of innovative primary care and community-based strategies for chronic disease prevention and management that will have a positive impact on the lives of British Columbians and Canadians. Strategies include collaborative ways to involve, in addition to family physicians, community caregivers (such as pharmacists), volunteer peer health educators, community-based organizations and patients in the research process.
Program: Scholar
Development of an Integrated Risk Assessment and Risk Management Tool for Health Care in BC, Phase 1 – assessment of chemical exposure hazards encountered by health care workers in BC
There are more than 80,000 health care providers working in BC. They work in complex and demanding environments where they may be exposed to numerous potential health hazards, including those that are chemical (e.g. drugs or cleaning agents), biological (e.g. bacteria or viruses) and physical (e.g. noise or radiation) in nature. Dr. George Astrakianakis focuses on understanding the many factors that determine the potential for exposure to health hazards among health care workers, and how to best mitigate their associated risks. In the initial phase of his research, he is identifying the specific chemical exposures commonly encountered in the healthcare workplace, assessing the risk to health for healthcare providers, and defining appropriate exposure control measures. In subsequent phases, he will assess biological and physical hazards, and implement and evaluate control strategies. Much of Astrakianakis’ data will be drawn from surveillance information collected by the Occupational Health and Safety Agency for Healthcare, which supports BC’s health care industry in part by monitoring information on occupations, exposure incidents and injuries among the Province’s health care professionals This information will form the basis for creating a job exposure matrix (JEM), which will be used to map exposure levels to occupations and eventually to provide risk estimates. The ultimate goal of this project is to design and implement appropriate exposure control strategies — such as technology, policy and training — in health care settings and to evaluate their effectiveness in mitigating risk to health care providers.
eVENT: An expert system for detecting ventilatory events during anesthesia
Despite the best intentions of clinicians many patients suffer adverse events during their medical care. As technology becomes more sophisticated and the amount of information generated increases, the risk that something goes wrong or is missed increases. The technology, work environment and clinical work flow needs to be designed to mitigate these risks. Technology has the potential to help clinician’s with tasks that humans do not perform well, such as vigilance, and reduce risk to patients.
Dr. J Mark Ansermino is a pediatric anesthesiologist with a background in health informatics and a particular interest in patient safety. He and his team are developing an expert system that automatically detects important changes in a patient’s status in the operating room. The clinician must divide his or her time between keeping an eye on the monitors, attending to the patient, and other tasks such as teaching students and giving drugs. Important events or evolving conditions can be missed. The technology will assist the busy clinician with attending to the huge amount of information generated by the monitors and bringing the important changes to the attention of the clinician. The system can also offer advice on what should be done about these changes and information on current treatment guidelines, providing the clinician with a recommended course of action in real time.
The current emphasis is on developing rules for a few dangerous events that affect breathing. This will be expanded to address other anesthesia-related events in the operating room. In this research, the system will be evaluated in both simulated and real clinical settings to determine if it is possible for clinicians to identify and respond to critical events more rapidly and reliably. This expert system will lend itself to promoting better decision making by both less skilled or experienced anesthesiologists during training or in situations where advanced training is not available.
The MTHFR C677T polymorphism and postpartum mental illness in at-risk women
Psychotic disorders (which include schizophrenia, schizoaffective and bipolar disorders) are common mental illnesses, affecting about 3 per cent of the population. Women face a number of challenges when dealing with these disorders, especially when it comes to pregnancy, childbirth and parenting. Women with a history of a psychotic disorder have substantial risks for a postpartum episode of mental illness like depression or psychosis. Postpartum mental illness carries risks for suicide and infanticide, as well as other less dramatic but still significant problems like difficulties with parenting skills and problems with mother-child bonding and attachment. Research has shown that, in general, psychotic disorders stem from interactions between genetic and environmental influences. The specific genetic variations that increase risk for postpartum episodes of mental illness are largely unknown. Dr. Jehannine Austin will use a new approach to investigate whether a variation to one particular gene contributes to risk for postpartum episodes of mental illness in women with a history of mental illness. This gene is known to encode a protein whose function is dependant on the B vitamin, folate. Dr. Austin will not only look at genetic variations, but will also measure folate levels in pregnant women at high risk of postpartum mental illness. If her work shows that the genetic variation plays a role in risk for postpartum mental illness, it may be possible to decrease risk for postpartum episodes of mental illness by providing folate supplements for these women.
Predicting the outcomes of cancer care services
With an aging population, rising costs and an increasing number of cancer cases, predicting the outcome of cancer care services is important for health care planning. Predictions can be based on computer models that take information from simple processes into larger systems. A model’s accuracy can be determined by comparing its predictions with real-world data and activity. As an MSFHR scholar, Dr. Chris Bajdik created a model to predict demand for hereditary cancer services in BC. He is now working to further develop prediction models for cancer care services. These new models will predict outcomes associated with cancer screening, treatment, supportive and palliative care. The predictions described through modeling will be compared with observed outcomes from provincial, national and international cancer care services. Dr. Bajdik’s approach provides a cost-effective way to predict outcomes – using the experience reflected in previously-collected data. Most importantly, these models will provide healthcare planners with a tool to predict the outcomes associated with new cancer care services and health policies. If the predictions are considered accurate, health care agencies can better plan and evaluate their services to care for those with cancer. The methods can be generalized to develop models for other forms of health care and other diseases.
Health Innovation Design and Evaluation (HeIDE)
In the last decade, the Canadian government has invested billions of dollars in development of a Canadian health information infrastructure. Health information technology goals are varied but they usually include faster, more efficient delivery of care based on shared information through electronic health records. However, despite the investment to develop an information technology infrastructure, the potential gains for the health system have been slow to materialize. Dr. Ellen Balka’s research focuses on the challenges associated with realizing Canada’s vision of an information technology-rich health care sector. She is working with stakeholders in actual health care settings, including technology developers, health system decision makers and health care providers, to assess design shortcomings, usability, implementation challenges, and issues related to governance of information technology within organizations. Dr. Balka’s studies will contribute to a more comprehensive understanding of how complex it is to introduce new information-based technologies into the health sector, and will lead to development of strategies that improve the rate of success for these initiatives within the health system. This will ensure that the potential benefits of these systems and technologies (administrative efficiencies, improved patient care and development of health data for research purposes) can be achieved.
Molecular Imaging of Cancer with Positron Emission Tomography
Recent developments in imaging devices provide researchers with powerful tools to detect cancers and explore the impact of therapy on tumour cells. This research program plans to leverage the strengths of positron emission tomography combined to computed tomography (PET/CT) to characterize and rapidly assess response to therapy in 3 common cancers (breast, prostate, and lymphoma) and combine this information with other predictors of aggressiveness and treatment failure. PET/CT imaging is a powerful technique that combines the strenghts of a PET scanner (which can measure tumor receptors and metabolic activity) with those of a CT scanner (which provides detailed images of a patient’s anatomy). The combination of both approaches could rapidly identify patients that are likely to fail conventional therapy and offer them alternatives that are better suited to the nature of their cancer. The research program is designed around 3 core themes. The first research them focuses on the development of methods to predict the outcome of patients with breast cancer who are treated with chemotherapy or hormone therapy. We will pursue ongoing work to develop animal models of breast cancer and imaging methods to monitor response of these tumors to chemotherapy and hormone therapy. We will also conduct clincial studies to correlate the results of imaging studies performed with PET/CT with outcome and response to therapy. The second theme focuses on the development of new probes that target specific proteins that are overexpressed at the surface of breast and prostate tumors. These probes might eventually be translated into clinical studies as breast and prostate cancer diagnostic agents for use with PET/CT, or even for therapy by tagging them with radioisotopes that can destroy tumor cells by proximity. The last theme proposes practical research studies of immediate clinical interest. We will assess the accuracy of PET/CT imaging in staging prostate cancer (with 2 radiopharmaceuticals designed to assess tumor lipid synthesis and bone turnover). We will also extend to the Vancouver site an ongoing study that assesses PET/CT imaging to predict the early response to chemotherapy in large cell lymphoma.
Carbohydrate recognition and metabolism in streptococcus pneumoniae: Structural and functional dissection of unique virulence factors
Pneumonia is an acute respiratory disease, the major cause of which is the bacterium Streptococcus pneumoniae. This bacterium is the leading cause of death from infectious disease in North America and a leading cause of death worldwide, particularly in children and the elderly. This bacterium can also cause meningitis, septicemia, and otitis media (middle ear infection). Reports indicate that 40 per cent of pneumonia cases caused by S. pneumoniae are resistant to penicillin and new multidrug resistant strains are beginning to emerge. To reduce increasing rates of antibiotic resistance and augment judicious use of the pneumococcal vaccine, alternative methods for treating S. pneumoniae infections must be found. Several proteins have been found in S. pneumoniae that are believed to contribute to its virulence. It is suspected some of these proteins destroy sugars such as glycogen in specific lung cells that normally serve to protect the lungs against infection. These damaging proteins are potential targets for preventing or slowing the infection. Dr. Alisdair Boraston will focus on two aspects of these S. pneumoniae proteins: if and how these proteins are destroying sugars and how to inhibit this activity. Biochemical studies will provide understanding about how these enzymes degrade sugars and whether any inhibitor molecules can interfere with this. Structural studies using X-ray crystallography will show structural features of the proteins that contribute to their activity and aid in the design of new inhibitors. Taken together, this information will lead to new approaches and agents to target pneumonia caused by S. pneumoniae.
Defining the structural basis of surface antigen glycoprotein mediated virulence in Toxoplasma gondii
Toxoplasmosis is a serious human pathogen carried by about one-third of the population. People develop toxoplasmosis either after ingesting undercooked meat that contains T. gondii cysts, or by coming into contact with cat feces from an infected animal. Once infected, healthy adults initially show a range of temporary flu-like symptoms; however, while these symptoms pass, the parasite Toxoplasma gondii remains in the body for life, with limited drug treatment available. Infection during pregnancy can cause miscarriage, neonatal death and a variety of fetal abnormalities, including developmental delays. It is also harmful to those whose immune systems are compromised, such as those with HIV/AIDS, cancer or who have had an organ transplant. Very little is known about how T. gondii causes disease. Dr. Martin Boulanger is studying the structure of host-pathogen interactions to determine the activities that allow T. gondii to attach to and invade human cells. With this information, treatments can be developed to prevent or manage Toxoplasmosis. This work will also apply to better understanding of other parasite-caused disease such as malaria and cryptosporidiosis.
Development and application of data standards for flow cytometry
Flow cytometry is a method of identifying and sorting cells and their components by staining with a fluorescent dye and detecting the resulting fluorescence (usually by laser beam illumination). Flow cytometry is widely used in health research (e.g. for stem cell identification and vaccine development), and in the diagnosis, monitoring and treatment of a variety of diseases, including cancers and HIV/AIDS.
Recent advances in high-throughput flow cytometry allows for the analysis of thousands of samples per day, creating detailed descriptions about millions of individual cells. Managing and analyzing this volume of data is a challenge that Dr. Ryan Brinkman is addressing through the development of data standards, algorithms, and bioinformatics tools. Dr. Brinkman is also applying these methodologies to the analysis of several large clinical flow cytometry datasets in an effort to identify biomarkers for lymphoma, neonatal auto-immunity, and graft versus host disease.