Trainee – Page 29 – Health Research BC

Design and discovery of novel organ specific iron chelating system for the treatment of transfusional iron overload

Iron is essential for different physiological functions and biochemical activities in the body, but is extremely toxic in excess. Because humans don’t have an active mechanism to excrete excess iron, too much iron in the system can lead to iron overload.

The mainstay treatment for many chronic anemia disorders is frequent red blood cell transfusions. Patients with such transfusion-dependent blood disorders are at a heightened risk of iron overload, which can cause severe damage to vital organs including the liver, heart, pancreas, thyroid and endocrine glands. Systemically accumulated iron is fatal if left untreated, and causes considerable morbidity and mortality.

Iron chelation therapy is the most widely-used therapeutic approach to improve survival and reduce the risk of iron overload, by chelating and excreting excess iron using small molecular Fe (III) specific chelators. However, the current FDA-approved iron chelators have many limitations, including inefficiency, toxicity, severe side effects, high cost, and patient non-compliance. Consequently, the lifespan of a major portion of transfusion-dependent anemic patients is severely narrowed. To date, no methods are available for the excretion of organ-deposited iron.

Recent developments in polymer/macromolecular therapeutic approaches shed new light on improving the therapeutic window of small molecular drugs and circumvent the limitations associated with existing therapies. Polymer therapeutics is a widespread multidisciplinary research area with a focus on polymer-conjugates of drugs and proteins, nano drug delivery systems and other macromolecular delivery systems. Several of such systems are approved for market arrival.

Dr. Abbina’s research will investigate improving the success and efficiency of iron chelation by incorporating biodegradable moieties in a polyglycerol scaffold, and targeting specific organs that are susceptible to iron mediated toxicity. The result of this research will be liver- and heart-specific macromolecular iron chelation systems.

The preliminary data is promising and we believe this safe and efficient therapeutic approach would benefit numerous patients suffering from iron overload induced diseases including cardiac failure or arrhythmia, cardiomyopathy, liver diseases and other endocrine disorders. This novel chelating system will also open new avenues to address other iron overload pathogeneses, including cancers, diabetes, inflammation and neurodegenerative diseases.

No time for nice? Exploring the nature and influence of workplace incivility and bullying in long-term residential care

Residential care aides (RCAs) provide the majority of hands-on care for individuals in long-term residential care (LTRC). Yet, as they are situated at the bottom of the workplace hierarchy, they receive little respect or recognition for their work. In BC, LTRC workers (mainly RCAs) have the highest rates of on-the-job injury; four times higher than the provincial average and twice as high as acute care workers, due primarily to overexertion and violent or aggressive acts from residents.
Little is known about RCAs’ experiences of peer workplace incivility and bullying, also known as horizontal violence. This is a significant gap, as staff turnover and absenteeism (factors which negatively impact residents’ quality of care and quality of life) are more correlated to exposure to workplace incivility and bullying than to patient threats and violence.

Quality person-centred care depends on respectful and collaborative relationships among RCAs; however, workplace incivility and bullying have the potential to significantly disrupt such relationships. For example, faced with workplace incivility and bullying, RCAs may lift or ambulate immobile residents alone rather than asking for help, putting themselves and residents at risk.

Using a critical ethnographic approach, this novel study will examine workplace incivility and bullying among RCAs in LTRC and its effect on care provision. Dr. Cooke’s findings will generate practice and policy recommendations for improving staff relationships that will, in turn, help improve residents’ quality of care and quality of life.

A Community Advisory Committee will provide input throughout the research process. Forums will be held periodically at each study site to share emergent findings, and a publicly-accessible, study-specific website will be created. Findings will also be shared with a variety of knowledge user groups (e.g., health authority residential care quality committees, UBC Centre for Research on Personhood in Dementia’s colloquium series, and the Patient Voices Network) to encourage dialogue and exchange. This will provide an opportunity to stimulate transformation in LTRC beyond the scope of the study sites and influence policy and practice across BC and potentially beyond.

Protecting insulin-producing beta cell transplants from death and dysfunction

Diabetes is one of the most common chronic diseases among adults, children and youth. In 2008/09, the Canadian Chronic Disease Surveillance System reported 2,359,252 cases of diagnosed diabetes in Canada and a prevalence of 5.4% in British Columbia. Rates of type 1 diabetes (T1D) among children and youth have been on the rise globally. Poor control of diabetes leads to various complications such as cardiovascular disease, stroke, blindness and renal failure, resulting in a shorter and a reduced quality of life.

One of the major pathologies in diabetes is a deficiency of insulin, which is secreted from pancreatic beta cells. Patients with T1D require insulin therapy throughout their life because most of their beta cells are destroyed by autoimmune attack. Even through insulin treatment, reduced glycemic control makes complications and hypoglycemia-induced coma more likely.

Islet transplantation is a promising therapy for T1D that removes the need for insulin therapy. However, some limitations remain such as the supply of donor islets, the need for lifelong systemic immune suppression, and graft failure. Today, human embryonic stem cell (hESC)-derived surrogate beta cells are in clinical trials; however, it is likely that these cells will not be protected from immune attack.

Dr. Sasaki will generate CRISPR-Cas9-edited hESCs that can be differentiated to beta cells that express CCL22 in order to protect hESC-derived islet cell graft from immune attack. If this approach is successful, the results of this study will further the optimization of functional and immune-tolerant surrogate beta cells, which will help pave the way towards a cure for T1D.

Study of Neurophysiology in Childhood Concussion (SONICC)

Dr. Julia Schmidt’s research investigates the neurophysiology of concussion (mild traumatic brain injury) in children and youth. Dr. Schmidt spent over 10 years as a clinician in brain injury rehabilitation (Australia and Canada) prior to engaging in research training in Australia. She seeks to better understand injuries in order to more effectively determine rehabilitation strategies.

Concussion is a major public health concern, particularly in children and youth due to their vulnerable developing brain. The neurobiology of recovery from concussion in children and youth remains largely unexplored. Dr. Schmidt aims to:

Sensitively quantify the severity and impact of concussion.
Map neurophysiological changes that occur acutely after concussion using transcranial magnetic stimulation.
Determine the time course of change associated with recovery from concussion.

Dr. Schmidt’s study will help to determine if the neurophysiology in children and youth are biomarkers of recovery. In turn, this can be employed as outcome measures in the development of new interventions and inform return to play decision-making.

Movement strategies for transferring without falling in older people

Falls are the leading cause of injury-related hospitalizations among seniors and a major cause of disability and death. About 30 percent of people over age 65, and 50 percent of older people in residential care, experience at least one fall per year. The risk for falls is mediated by various physiological, behaviour and environmental factors, but ultimately depends on the frequency of imbalanced events and abilities to successfully recover balance.

One of the most essential and fall-prone activities for older people is transitioning from sitting to standing. Even though imbalance occurs frequently during transfers, not all transfers result in falls. Our understanding of what determines the success of sit-to-stand transfers is limited. This project will use video and wearable sensor technology to clarify environmental and biomechanical differences between successfully and unsuccessfully performed sit-to-stand movements in older people as they go about their daily activities. In complementary experiments, the project will examine the role of muscle power as an underlying mechanism for successful transferring.

This project has two objectives:

Quantify the importance of avoiding imbalance vs. recovery of balance in sit-to-stand transfers.
Identify the importance of muscle power for sit-to-stand performance in older people.

Objective 1 – Our research group is involved with an ongoing collection of video footage and wearable sensor data of mobility and falls in older people in long-term care. This project will contrast successful vs. unsuccessful transfers (resulting in falls) in individuals to identify strategies to prevent imbalance and attempts to recover balance (e.g. through muscle torque generation or through change in support, stepping and grasping). It will further quantify biomechanical characteristics of recovery attempts (e.g. size, direction and timing). This analysis will provide new ecological insight on the importance of avoiding imbalance vs. successfully recovering balance for older people prone to falls when transferring.

Objective 2 – The ability to plan and execute movements is a complex process that relies on sensory, cognitive and neuromuscular systems. This project will test the hypothesis that speed modulation is a key determinant of success for the task of rising from sitting, and that speed modulation will relate to lower limb power — a target amenable to improvement through exercise. These findings will contribute to current knowledge by identifying the key muscle functions for rising from sitting, to guide the development of a personalized intervention for those individuals at high risk for falling during transfers.

This project will ultimately provide key information on the cause and prevention of mobility impairments and falls in older people.

Identifying prodromal signs of multiple sclerosis: a multi-centre approach

Multiple sclerosis (MS) is a neurodegenerative disease for which there is no known cure. It is among the most common causes of neurological disability in young adults in the Western world and affects approximately 2.3 million people worldwide, including an estimated 75,000 Canadians. The symptoms of MS and related morbidity have a major impact on quality of life: weakness, fatigue, disability and depression can all influence social, family and work life.

Some intriguing preliminary findings from one study based in Manitoba indicated that people with MS had more medical consultations than people without MS, even throughout the five-year period prior to MS onset. This implies that the disease already starts to develop long before the currently recognized clinical onset of MS. However, these findings have yet to be replicated and it remains unknown as to what the reason(s) were behind the measurable increases in medical consultations.

The aim of this project is to search for early signs and symptoms that could facilitate more timely recognition of MS and to narrow down the relevant time window when searching for factors triggering MS.

I will examine databases of medical records from people with MS in British Columbia, Saskatchewan, Manitoba and Nova Scotia. I will explore their physician and hospital visits before MS onset and before MS diagnosis, and I will compare this data to medical information from the general population. I will also examine the reason(s) for the physician and hospital visits.

I hypothesize that among people who go on to develop MS, I will identify specific associated “disorders” that drive the elevated health service utilization before MS onset.

I will help the research team share the findings directly with BC provincial decision makers via one-on-one meetings and presentations. Connections with patient advocate groups will enable me to also raise awareness of the results among people with MS.

Ultimately, the results of this study could contribute towards an earlier recognition of MS.

Understanding health equity and resource development (UnHEARD): New tools for assessing the health equity implications of unconventional natural gas development on rural and remote communities in northern British Columbia

Resource extraction and development activities are the primary drivers of social and economic development for communities across northern Canada, and therefore are significant determinants of community well-being. However, there is growing global recognition that the benefits of resource development are not distributed evenly across the supply chain, and that new tools are required to understand how anthropogenic changes in the natural environment affect population health.

This study uses the case of unconventional natural gas development in northern BC’s rural and remote communities to enhance the scientific understanding between resource development pathways and human health. BC is currently preparing for the rapid development of its natural gas reserves in conjunction with other diverse forms of land use and development (e.g. forestry, mining, industrial agriculture, etc.). However, the health impacts of rapid industrial growth are not well understood, and differences will be abound between gas extracting regions in the northeast of the province, gas transportation corridors through the northern interior, and gas exporting communities on the northwest coast.

In seeking to contextualize health impacts associated with resource development across the supply chain, this research will work to develop a new health equity impact assessment tool that is rooted in international best practices to explicate the intersections between ecosystems, the boom and bust cycle of resource-dependent towns and regions, and the resulting impacts on human health which are often overlooked in existing provincial environmental assessment and cumulative effects assessment protocols. Indeed, an explicit focus on health equity is a purposeful way to understand how health impacts are distributed across time and geographic space related to rapid resource development, thereby giving voice to health issues that often go UnHEARD during project permitting and planning. This work will involve the integration of a variety of data types to track changes in the distribution of health outcomes over time, and enable the identification of programs and protocols capable of mitigating associated health risks. Accordingly, this research will inform provincial regulatory processes through an expanded understanding of environmental disturbance as a context for health promotion, while assisting regional stakeholders in minimizing harmful impacts of industrial activities on community and worker health.

The Effect of Psychosocial Stressors on Health Behaviours and Indicators of Cardiometabolic Risk in the Transition to Young Adulthood

Adolescence and young adulthood are critical periods for health promotion and disease prevention. Cardiometabolic risk (CMR) refers to a set of indicators that increase an individual’s risk for diabetes, heart disease or stroke. These indicators start to show predictive variability in adolescence and identification and implementation of early strategies for risk management can have significant long-term health benefits. Much of what we know about CMR comes from studies of adults; therefore, research focusing on earlier age groups is needed.

The first objective of the proposed research is to describe the frequencies of select, non-invasive CMR indicators, including body mass index (BMI), systolic and diastolic blood pressure (BP), and waist circumference in young adulthood (ages 22-29). Research in psychoneuroimmunology documents the deleterious effects of stress on physical health; however, less attention has been given to adolescents and young adults.

The second objective is to examine how psychosocial stressors that become salient in adolescence (e.g. internalizing symptoms and interpersonal stress) predict CMR.

The third objective is to examine how these stressors compromise the enactment of key health behaviours (e.g. physical activity, eating habits, sleep duration) leading to increased CMR.

The project will use six waves of the Victoria Healthy Youth Survey (V-HYS), a 10-year longitudinal study that surveyed youth (N = 662) biannually from 2003 (T1; ages 12-18) to 2014 (T6; ages 22-29). In-person measurements of CMR (BMI, systolic and diastolic BP, waist circumference) were collected at T6. Measurements of internalizing symptoms, interpersonal stress (e.g. peer victimization), and health behaviours were collected at each wave.

Findings will highlight the variability in CMR in young adulthood and increase knowledge on the effects of two salient stressors on CMR from adolescence to young adulthood, providing new information about targets for prevention and interventions. The results will also inform guidelines for early identification and preventative healthcare.

Knowledge translation efforts will include 1) peer-reviewed publications, conference presentations, media reports, and policy formats; 2) creating an infographic about CMR in young adulthood to release to the media; and 3) developing a training tool to educate healthcare professionals about the relations between stress and CMR in these young age groups.

‘APP’lying Supportive Movement: Trauma-Informed and Culturally Safe Physical Activity Programming for Young Pregnant and Parenting Women Marginalized by Poverty, Racism, and Trauma

Physical activity has been found to have numerous physical, emotional and psychological benefits, particularly for young pregnant/lone parenting women (YP/LP). Unfortunately, physical activity declines through adolescence, and women who are marginalized by poverty and racism have lower levels of leisure time. There is a lack of research on physical activity for YP/LP women who are marginalized by poverty, racism, and/or trauma, thus little is known about the barriers and facilitators for physical activity for this population. Physical activity is especially important for these women because they have a greater risk for obesity, anxiety, depression, low self-esteem, and PTSD.

My proposed mixed methods participatory research will focus on physical activity with YP/LP women who are marginalized by poverty, racism, and trauma – arguably some of the most marginalized women in Canada. My research has the following objectives:

Assess current health and physical activity behaviours engaged in by YP/LP women.
Understand the perceived barriers and benefits of physical activity for these women and establish strategies to support YP/LP in a culturally safe and trauma-informed manner.
Assess if existing quality of life measures are relevant for this population and determine if there is a correlation between quality of live and physical activity levels for these women.
Translate the knowledge gained to create a technologically-enabled approach to support/improve YP/LP well-being.

This research will take place with partnering organizations on Vancouver's Downtown Eastside that serve pregnant and parenting women. I will work with participants to create and implement a technology-enabled health intervention that is culturally safe, age relevant, trauma-informed, and cost effective.

Understanding the evolution of expectant and new parents’ beliefs and behaviours about pediatric vaccination in British Columbia

Vaccines are the most effective way to prevent many communicable diseases, yet immunization rates in British Columbia are below the level required to mitigate outbreaks of infectious diseases. This can be partly explained by some parents’ doubts and concerns about pediatric vaccinations, termed “vaccine hesitancy”.

Numerous interventions have tried to address these concerns by focusing on communication between physicians and parents when their child is already several months old. Yet there is evidence that some parents make decisions about their child's vaccinations even before the first mention of vaccines in doctors’ offices or public health clinics; this makes the pre-natal period a potentially underutilized opportunity for initiating vaccination communication. Parents’ beliefs may also change over time in response to new information or conversations within their social networks.

As mothers are the primary decision-makers about vaccination, understanding maternal beliefs about pediatric vaccination is essential to ensure effective messaging and service delivery. It is also crucial to understand the beliefs and preferences of fathers and other co-parents, given the important role they play in shaping vaccination decisions.

Few studies to date explore how parents’ vaccination beliefs shift over time, particularly how parents’ beliefs before the baby is born continue to evolve during the first few months of their child’s life, and none to our knowledge in regions of BC where immunization rates are well below the Canadian average. Parental attitudes on southern Vancouver Island reflect specific local vaccination cultures and thus, may vary significantly from those on the mainland.

This longitudinal qualitative study explores decision-making processes about vaccinations among expectant and new parents in Victoria, BC by conducting four interviews with each mother, and two interviews with fathers or other co-parents, from the third trimester until just after the child’s first birthday. Analysis will focus on identifying points of leverage that may inform future interventions, providing data on the optimal time and method to engage parents.

Knowledge translation is integrated into the study design through collaborations with Island Health. Findings from this study will be presented for discussion in workshops with key stakeholder groups, disseminated through publications and conference presentations, as well as via a short radio piece.