Building the Evidence-base to Support Rural Maternity Health Services Policy and Planning

Dr. Stefan Grzybowski is a family physician clinical investigator and co director of the Centre for Rural Health Research within the Vancouver Coastal health Research institute. He is co-Principal Investigator of the Rural Maternity New Emerging Team, funded by the Canadian Institutes of Health Research and also co directs the British Columbia Rural and Remote Health Research Network, a Health of Population Network funded by the Michael Smith foundation. Prior to moving to Vancouver in 1994, Dr. Grzybowski practiced for 12 years as a family physician on the Queen Charlotte Islands/Haida Gwaii.

Dr. Grzybowski’s research has focused on building an evidence base supporting sustainable maternity health services for rural parturient women, translating this evidence into policy and practice and building research capacity for primary care clinician researchers. His interest in rural health services research was fostered by his experiences in facing the challenges of providing limited maternity services in an isolated hospital on the Queen Charlotte Islands without local access to Cesarean Section. His current projects include developing a Logic Model for sustainable rural maternity care in three isolated BC communities, investigating mechanisms in which GP surgery can be supported in BC, measuring population based maternal and newborn outcomes for rural service catchment areas across BC, and measuring stress associated with pregnancy for parturient women living in rural communities.

Individual differences in stress coping and predisposition to disease.

Glucocorticoids are hormones that the body releases into the bloodstream in response to stress, protecting our bodies in the short term against the damaging effects of stress. Chronic oversecretion of these stress hormones can lead to various mental health disorders such as anxiety and depression. Humans show extreme differences in how they adapt or succumb to the pathological effects of stress. Sex steroids play a critical role in individual and gender-based differences in stress-induced pathology, but the basis for this in the central nervous system is not understood. Independent studies in rodents and humans show that testosterone can regulate the magnitude of the glucocorticoid and behavioural responses to stress. With this data, Dr. Victor Viau is working to determine how testosterone operates on stress-related pathways in the brain, from a physiological and chemical perspective. He is investigating how early-life exposure to testosterone determines the brain’s response to stress during adulthood, and providing insights about the underlying factors that allow the individual to manage stress in different ways. Viau’s research program is unique as it aims to determine how, where, and when stress and testosterone interact in the nervous system and at the hormonal and behavioural levels. The research will ultimately provide a fundamental framework for understanding why some individuals succumb to the psychopathological effects of stress and others persevere in the face of it.

Identification of a novel obesity gene

The prevalence of obesity is increasing dramatically, and is occuring at an increasing rate among children. Obesity is a major risk factor for numerous diseases including diabetes, heart disease, high blood pressure, stroke, arthritis, and some forms of cancer. Inherited factors strongly affect an individual’s risk for becoming obese, especially in an environment with little exercise and diets high in fat and sugar. However, many of these genetic factors are not yet known.

Dr. Susanne Clee’s research seeks to identify one of these genetic factors. She is conducting genetic studies on mouse strains that differ in their risk of developing obesity when fed a high fat diet. Clee will progressively zero in on new candidate genes by comparing the suspected region’s DNA sequence between obese and non-obese mice, and identifying specific changes in genes that could lead to the development of obesity. At the same time, Clee will use these mouse strains to study the biology of how obesity develops. By comparing mice that become obese when fed a high fat diet compared to mice that resist obesity, she will be able to describe how the body's processes are altered as individuals become obese.

By identifying new genetic factors that cause mouse strains to become more obese, Clee hopes to gain a more specific understanding of how obesity develops. This knowledge will lead to new ways to treat or prevent this disease and to identify those individuals more at-risk of developing obesity.

Role of the startle reflex and cervical multifidus in whiplash injury

Low-speed rear-end collisions can generate whiplash injuries, especially when the victim is unprepared for the collision. Neck pain is the most frequent symptom experienced by victims of a car collision, and up to 30% of people injured in a car collision will develop chronic symptoms. In fact 6% of people who develop chronic whiplash from a collision have not returned to work 12 months after the injury. The precise cause of whiplash is not known, but an overreaction in unprepared individuals — known as a startle response — along with the sudden recoil movement of the head, is thought to damage the joints and muscles of the neck.

As an MSFHR-funded post doctoral fellow, Dr. Jean-Sébastien Blouin conducted research that suggested the presence of a startle response when people are exposed to low-speed rear-end collision. Now he is investigating whether the startle response is linked to stimulation of the deep neck muscles, and if activation of these muscles during a collision may increase the risk of injury. With volunteers acting as “crash test dummies,” Blouin is simulating very low speed (1.8 km/hour) collisions to observe their startle response and measure the corresponding muscle activity. He’s investigating the link between a strong startle response during a low speed collision and the development of whiplash symptoms. He’s also exploring if stimuli delivered immediately prior to the collision can inhibit the startle response, possibly providing protection against injury. Findings could contribute to development of a warning device in cars that will help prevent whiplash injuries.

Voltage-gated sodium channels as modulators of electrical excitability in the heart and therapeutic targets in the management of atrial arrhythmias

Electrical disturbances in the heart are a serious health threat for many people. For example, cardiac atrial arrhythmias (a type of irregular heart beat) affect 4% of people aged 60 and older, and have an associated fivefold increase in stroke. As our population ages, this incidence is expected to increase up to 2.5 times over the next half century. Cardiac membrane proteins called ion channels control the flow of sodium and potassium in and out of heart cells, regulating both the cardiac electrical impulses and the contractions associated with the heart beating. Dr. Christopher Ahern is interested in drugs that interact with the sodium ion channel to correct atrial arrhythmias. Although these drugs are widely prescribed, scientists still don’t fully understand exactly how they work. More critical is that these drugs can become lethally toxic in cases where the arrhythmia co-exists with other common heart problems, such as an enlarged heart. This dangerous shortcoming seriously limits their use for many people who could otherwise benefit from their therapeutic effects. There is a need for better anti-arrhythmic therapies – ideally, designer drugs for atrial arrythmias that exploit the positive attributes of current therapies while minimizing their negative side-effects. Dr. Ahern is using new chemical methods that are providing much more detailed information about how these drugs bind to and interact with the sodium channel. Using these new methods in combination with computational approaches that bypass previous limitations with the research, his team will take a fresh look at drug binding and ion channel function with the goal of designing safer anti-arrhythmic drugs

Transformational teaching and physical activity adherence among adolescents: From measurement and prediction to intervention

Physical inactivity in adolescence has been linked to a vast array of physical and mental health problems that extend across the lifespan. Canadian adolescents are required to undertake regular physical education as part of their school curriculum, guided by physical education teachers. However, more than half of adolescents are considered not sufficiently active to meet international guidelines for optimal growth and development. In workplace settings, “transformational leadership” is exemplified by business leaders whose behaviours and interactions inspire employees to reach new heights of work performance and self confidence. Transformational leaders inspire, energize and intellectually stimulate their followers. Training programs in business and military settings have also shown that people in leadership positions can successfully acquire and develop these behaviours.

Exercise and health psychologist Dr. Mark Beauchamp is taking this leadership model out of the workplace and applying it to school physical education and health promotion settings. He’s studying whether training physical education teachers in transformational leadership can positively affect the attitudes and behaviours of their students around adopting and maintaining physical activity. If this approach is proved effective, this research could be used to help develop evidence-based initiatives (across Canada and beyond) that inspire a greater proportion of adolescents to become and stay physically active.

Understanding how cationic antimicrobial peptides and lipopeptides function in order to design better antibiotics

With the ever-increasing prevalence of antibiotic resistance, it has become critical for scientists to develop alternatives to antibacterial agents and offer long term sustainable health care solutions. Bacterial resistance to common antibiotics has a dramatic impact on hospital and community health care, affecting entire hospital wards and communities. This creates significant – and largely avoidable – pressure on current health care budgets. Two types of microbe-fighting peptides are generating much interest as potential alternatives to current antibiotics: cationic antimicrobial peptides (CAPs) and anionic lipopeptides (ALs). Both types of peptides are commonly found in nature and have remained effective, displaying little to no antibiotic resistance effects. Both are believed to act by targeting and perturbing the bacterial membrane, which eventually leads to cell death – a process that is strikingly different from current antibiotics. Dr. Suzana Straus aims to find novel alternatives to current antibiotics by investigating how promising candidates from the CAP and AL peptide families function and by designing more potent versions derived from these candidates. Her work is focused on three peptides: two CAPs from amphibians and one AL called daptomycin, which is known to be effective against particular complicated skin infections. Straus is researching the structural and functional properties of these membrane-associated peptides and proteins, which is crucial in the design and development of new and effective medicines. Ultimately, her work will provide insight into which factors should be considered in the design and development of a new generation of antibiotics.

Extracellular Matrix Adhesins of Treponema pallidum

Syphilis, caused by the bacterium Treponema pallidum, is a chronic bacterial infection with a global distribution. Although this sexually transmitted disease is 100 per cent curable with penicillin, syphilis remains a health threat, with an annual incidence rate of 12 million active infections. In BC, new cases are being reported at almost double the national rate. Unchecked, the infection can damage every tissue and organ in the body, including the brain. Equally troubling, syphilis infection drastically increases vulnerability to HIV infection. Treponema pallidum is a highly invasive pathogen; following attachment to host cells, the organism invades the tissue barrier and enters the circulatory system, resulting in widespread bacterial dissemination. Little is currently known about the mechanisms this bacterium uses to initiate and establish infection.

Dr. Caroline Cameron has the only laboratory in Canada conducting basic research on this bacterium. She is using cutting-edge proteomic technologies to study two molecules that enable the bacterium to attach itself to host cells lining the bloodstream – a critical step in the development of infection. By understanding these mechanisms, Cameron hopes to identify potential ways that scientists could interfere with adhesion and disrupt the infection process. Ultimately, her work could lead to development of a vaccine to prevent syphilis.

Cognitive decline through normal aging to dementia and death: Identifying early risk factors and targeting effective interventions

The number of Canadians older than 65 is steadily increasing, a trend that will continue over the next few decades. The prevalence of age-related disorders such as dementia is also increasing, along with the related need for personal care and treatment. Cognitive impairment adversely affects quality of life in late adulthood, limiting independence and survival. To examine these important health issues, Dr. Stuart MacDonald is studying factors related to age-related declines in cognitive performance. Part of his research employs existing data from a Swedish study (the Kungsholmen Project; http://www.kungsholmenproject.se/) to examine patterns and identify early predictors of cognitive decline. As the average age of the Swedish population far exceeds that of Canada, research on the Kungsholmen data may provide important insights that can help inform Canadian healthcare policy and prevention strategies.

Dr. MacDonald is also researching how performance for select measures of memory and intelligence is influenced by cognitive training across a period of weeks, as well as regular aerobic exercise (walking three times per week for 30 minutes) over a period of months. Dr. MacDonald's goal is to clearly demarcate the stages and transitions of cognitive decline from mild age-related impairment to more severe dementia deficits. This will help identify early warning signs of cognitive impairment from a broad range of predictors. The findings could lead to more effective prevention based on knowledge of these risk factors, including campaigns to promote health-smart behavior.

Reconceptualizing the Formation of the Therapeutic Alliance from the Patient’s Viewpoint using a Mixed Methods Research Design

The nature of the relationship between a healthcare provider and an individual receiving care has an impact on the success of psychotherapy and drug therapy. A strong professional working relationship can not only enhance the effect of psychological and psychiatric interventions, but can be therapeutic in and of itself. This has even been found in the treatment of very serious psychiatric conditions such as bipolar disorder and schizophrenia. Researchers have estimated that as least 30% of the effectiveness of psychotherapy and drug therapy can be accounted for by the quality of the professional relationship between an individual and his/her mental healthcare provider. There is a lack of understanding about the factors that are most important for developing a solid working relationship from the perspective of the individuals receiving the mental health services. Expanding upon research he conducted as a MSFHR trainee, Dr. Robinder (Rob) Paul Bedi is exploring this area. He is interviewing individuals currently receiving mental health services and analyzing the variables that they identify. The result: identifying the most common factors found to be essential in the development of positive therapeutic relationships. Bedi’s research aims to help mental healthcare providers develop strong working relationships with the individuals they treat, resulting in improved overall effectiveness of the mental health services that individuals receive.