Trainee Archives - Page 38 of 160

Development and Validation of the Patient Engagement In Research Scale (PEIRS)

Patient engagement in research occurs when patients meaningfully and actively take part in the conduct and decision-making at any stage of the research process from inception through impact evaluation. There is a paucity of validated measurement tools to evaluate whether interventions to improve patient engagement in research support their successful engagement.

This project aims to develop and validate the Patient Engagement In Research Scale (PEIRS) for use by patients who partner in health research (i.e. patient partners), and to evaluate the degree to which they are meaningfully and effectively engaged in the research process. PEIRS will be developed with patients for patients. Our key objectives are to generate an item-bank reflecting the elements of patients’ experiences as partners in research; use the most relevant experiences to develop the PEIRS; then, evaluate the validity and reliability of PEIRS.

We will used a mixed qualitative and quantitative study design. First, a secondary thematic analysis will be conducted on in-depth interviews of 20 patients with arthritis who have experience as research partners. An extensive list of items relevant to the quality of patient-researcher partnership will be developed. Second, we will invite 10 patient partners to participate in a Delphi process to prioritize, select, and modify the items. We will then conduct usability testing with another 10 patient partners to identify and address any problems in the provisional PEIRS. Third, we will recruit 100 patient partners from across Canada to test the PEIRS’s validity and reliability. Specifically, factor analysis will examine its structural validity. Concurrent validity of PEIRS will be tested against an established measure of overall satisfaction and experiences of the public and patients as project partners in a health system organization. In addition, we will assess the association between PEIRS scores and participants’ ratings of the “meaningfulness” of their engagement.

This research project employs an integrated knowledge translation approach, in which researchers and experienced patient partners are working together at every stage of the research process, from inception through knowledge translation. PEIRS will address an important barrier to advancing the science and practice of engaging patients in research, namely the lack of a validated measure to assess effectiveness of patient engagement strategies. As such, this research contributes to support meaningful engagement of patients in health research.

Improving health equity through cross-cultural collaboration: Learning from Indigenous-developed programs to strengthen public health systems in preventing the harms of substance use in BC

A function of public health systems and services is to reduce health inequities. The harms of substance use impact British Columbians differently based on their social position and access to resources. Over the last decade, BC has had renewed interest in health equity as demonstrated by several key policy documents. Initial research findings however, have demonstrated that the application of a health equity lens is a challenge for public health decision makers and practitioners. However, for many public health service providers, First Nations and Aboriginal health organizations and service providers are seen as leaders in the understanding and application of health equity principles.

Accordingly, there is an immense opportunity in BC for collaboration and learning with First Nations and Aboriginal health partners to optimize health equity for all British Columbians. Despite these opportunities, little is known about the synergies between Indigenous knowledge and health equity strategies related to the reduction of harms of substance use in BC. In particular, more research is needed to understand if Indigenous approaches to health and wellness can be imported into the current BC public health system and to explore how Indigenous-developed programs and services can inform health equity strategies related to reducing the harms of substance use in BC public health systems and services.

This research project will be one of the first to systematically examine how health equity strategies in the BC public health system could benefit from Indigenous knowledge and worldviews. This project has the potential to impact the health of all British Columbians by informing the development of more equitable health programs and services. In addition, by prioritizing Indigenous ontologies and processes, this project also has implications for how Aboriginal communities in BC are perceived and esteemed, thereby having the potential also to specifically improve the well-being of those communities. In addition, this prioritization has the potential to mitigate epistemological colonialism and shift power relations which are integral in promoting health equity for Indigenous peoples.

Dr. Shahram received a 2017 Health Policy Fellowship to promote Indigenous health in BC’s southern interior by integrating cultural safety and health equity assessments into the fabric of the Interior Health. Her 2016 Trainee Award will placed on hold during her health policy fellowship assignment.

Neural correlates of symptom provocation in pediatric obsessive-compulsive disorder (OCD)

Pediatric obsessive-compulsive disorder (OCD) is a neuropsychiatric illness that has a 1-4 percent prevalence rate in children and youth. OCD is characterized by intrusive thoughts and repetitive behaviours, and although treatments, such as cognitive behavioural therapy (CBT), are available, better treatment selection could improve response rates.

To advance our understanding of the dysfunctional brain mechanisms underlying OCD, and eventually find predictive biomarkers of treatment response, functional magnetic resonance imaging (fMRI) has been used to find the neural correlates of OCD, particularly during symptom provocation tasks (i.e. tasks that allow researchers to probe the brain areas involved in emotional processing by exposing OCD patients to OCD-related stimuli). This research has given us neural correlates of OCD, but fMRI is expensive to implement in clinics.

The goal of this proposal is to use electroencephalography (EEG) to study OCD symptom provocation because it is less costly than fMRI and easily implemented in clinics. EEG also provides an innovative way to investigate OCD, as it provides a fine-grained temporal measure of brain activity, whereas fMRI provides a fine-grained spatial measure of brain activity. Thus, EEG could provide a new set of temporal psychophysiological correlates of OCD that would be easily and inexpensively collected in clinics, and that could predict CBT outcome. In the proposed study, clinically diagnosed pediatric OCD patients (12-18 years old), siblings unaffected by OCD (12-18 years), and matched healthy controls (HCs) will complete an OCD symptom provocation task that elicits emotional responses while EEG is recorded. Event-related potentials (ERPs) will then be derived from the EEG data and will be used to characterize the OCD group in comparison to the sibling and HC group, and to use as potential predictors of CBT response.

The proposed study is novel because few EEG studies of OCD symptom provocation exist, and no emotional-related ERP studies have been conducted in children, although pediatric studies are essential to our understanding of early brain differences.

Our findings will be presented to clinicians and researchers at annual conferences and published in leading peer-reviewed journals. Lay-friendly articles will also be written and submitted to the Canadian OCD Network’s and the International OCD Foundation’s newsletters.

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:

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).
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.

Changing cognitions to change behaviour change: Reframing biased thinking to improve exercise adherence in individuals with prediabetes

Pre-diabetic individuals exercise less than their non-diabetic counterparts, with less than 15 percent meeting Canada’s physical activity guidelines. Behaviour change techniques (BCTs) such as self-monitoring and provision of goal feedback are key components of interventions for cardiovascular risk factor reduction. However, patients in such programs may not accurately interpret risk information and fail to act in ways that reduce or prevent risk. Individuals at risk for type 2 diabetes (T2D) who exhibit biased thinking (e.g. all-or-nothing thinking; “Going for walks is not going to prevent me from getting T2D”) may not be ready to engage in risk-reducing behaviours. For this reason, reframing biased thoughts may offer a critical pre-intervention (pre-IV) step that prepares them for future attempts at behaviour change.

The purpose of this study is to examine cognitive reframing as a pre-IV strategy for individuals at risk of T2D about to embark on a brief exercise counselling intervention. The main hypothesis is pre-IV cognitive reframing will increase:

Individuals’ self-regulatory efficacy
Compliance with brief exercise counselling
Independent exercise adherence

Cognitive reframing is an evidence-based strategy for reducing biased thinking in health contexts whereby individuals are taught to identify and challenge biased thinking caused by cognitive errors. This study will employ a randomized experimental design (intervention VS control group) to examine the effectiveness of pre-IV reframing for individuals at risk of T2D who experience biased exercise thoughts. The proposed research will be embedded within Dr. Mary Jung’s ongoing randomized control trials examining brief behavioural change IVs for people living with prediabetes in the community.

Results will partly be disseminated by coordinating a community-based prediabetes exercise clinic within Kelowna, and by working directly with Interior Health, the Kelowna Diabetes Program, and the Central Okanagan Division of Family Practitioners.

This novel research program seeks to triage individuals at risk of T2D with biased exercise thoughts. Findings may better prepare individuals with prediabetes struggling with a lifestyle change to be more receptive to receiving BCTs and attempt risk-reducing behaviour.

Open MRI for assessing joint biomechanics – applications for osteoarthritis

Hip osteoarthritis is prevalent, disabling and costly to individuals and the healthcare system. Symptomatic hip osteoarthritis affects 4.2 percent of people over 50, and radiographic degenerative changes are seen in almost 20 percent of the same population. In many patients, total hip arthroplasty is used to relieve pain and improve function. Though effective in improving a patient’s quality of life, joint replacements will eventually fail and require revision surgeries that have a higher complication rate and less predictable results. Better strategies to delay or stop the progression of osteoarthritis are needed, which can only be created with a clearer understanding of the disease’s etiology.

While there is strong evidence that structural changes around the hip are major etiological factors in the development of osteoarthritis, it is not clear how to protect hips from the disease. Anatomical abnormalities such as cam-type femoroacetabular impingement (a deformity of the hip bones) may account for 90 percent of hip osteoarthritis cases. However, it is not clear why only some people with these deformities get hip osteoarthritis. It is widely assumed that the relationships between activity and deformity size and their effect on joint mechanics are critical. Investigating these relationships has not been possible to date because there have been few well-validated methods for assessing impingement directly in vivo. This project will answer two research questions:

Which activities lead to direct cam impingement at the hip in patients with FAI deformities?
How is this impingement influenced by deformity size?

To answer these questions, we will use gait analysis to measure hip movements and mechanics in symptomatic and healthy subjects for a range of activities associated with hip pain. These measurements will be used to develop subject-specific numerical models predicting direct impingement for each participant. Model predictions of direct impingement will be validated by scanning participants using an established protocol in UBC’s upright open MRI scanner.

We have developed a knowledge translation strategy for this project with the Arthritis Patient Advisory Board; they will post the project summary on their website as well as profile the research findings on social media. Results will be published in both clinically- and research-oriented journals and at conferences for both clinicians and scientists.

Advances in the treatment of sexual dysfunction in men: Applications for mindfulness-based cognitive therapy

One in eight men will be diagnosed with prostate cancer in their lifetime. Advances in prostate cancer treatments mean that the number of prostate cancer survivors is higher than ever; however, prostate cancer treatments come with side effects, many of which are life-long. Up to 90 percent of prostate cancer survivors will go on to experience erectile dysfunction (ED) — difficulties obtaining/maintaining an erection sufficient for sexual activity that can be highly distressing for both men and their partners. Although some medical treatments for ED exist (e.g. Viagra), these medications tend not to be very effective for these men.

Mindfulness (non-judgmental present-moment awareness) is a new tool in sex therapy that has been shown to be effective in treating women with sexual dysfunction. Mindfulness has also been shown to have psychological and physiological benefits for men who have survived prostate cancer (for example, it improves quality of life as well as immune system functioning in these men). The current research study aims to take the same mindfulness-based sex therapy that is effective for women, and adapt it for men with ED following prostate cancer treatments and their partners.

Men experiencing ED following prostate cancer treatment will be recruited from the Vancouver Prostate Centre to take part in a mindfulness-based group therapy. Men will be randomized to either an immediate or a delayed treatment group. The group will consist of six to eight other men and their partners, and involves two-hour sessions for four consecutive weeks, with home practice activities in between sessions. Content of the sessions will include education, elements of sex therapy, and mindfulness training. We predict that mindfulness therapy represents a new and important treatment that will ultimately help improve quality of life in the growing number of men who experience ED following prostate cancer treatments.

This project will examine optimal combinations of psychological and medical care for men with ED following treatment for prostate cancer and their partners, with the ultimate goal of improving conceptualization and treatment. In order to increase men’s access to sexual health care, knowledge translation is pivotal. I will collaborate with Dr. Lori Brotto and Dr. Tia Higano to share the findings with academics (e.g. conferences, publications) and stakeholders (e.g. media), and train clinicians to deliver MBCT for men (e.g. clinical psychology students at UBC, paraprofessionals in sexual health clinics across UBC and Vancouver hospitals).

Neurally-produced estradiol enhances the neuroprotective actions of insulin

Alzheimer’s disease is a debilitating disorder that is on the rise in British Columbia’s aging population. A growing pool of evidence suggests that Alzheimer’s disease may involve insulin, a hormone whose activity in the pancreas is linked with type 1 and type 2 diabetes. Insufficient action of insulin in the brain can be a cause of Alzheimer’s disease, which is increasingly being called “type 3 diabetes” because of this.

During my graduate studies, I observed that insulin is produced in the brains of mice and humans, with highest expression in the hippocampus. My preliminary results also suggested that deletion of brain insulin in mice leads to cognitive deficits.

Estradiol enhances insulin production and response in the pancreas. However, these effects of estradiol in the brain have never been confirmed. Yet when expressed together in the hippocampus (a brain structure critically involved in memory), estradiol and insulin promote neuron growth and survival as well as synapse formation and maintenance.

I will test the hypothesis that estradiol produced by neurons enhances the production and action of insulin in the brain, and that this has beneficial effects in a rat model of Alzheimer’s disease.

I will inhibit estradiol production in the brain and then test how local insulin expression and signalling are affected in the brains of the rats. I will also examine the neurons and synapses in adult rats and will perform behavioural and cognitive tests. A drug that blocks insulin receptors will be used to confirm that insulin signalling is the true cause of any changes I observe.

I predict that inhibition of brain estradiol production will reduce brain insulin expression/action and increase negative effects associated with Alzheimer’s disease in this rat model.

Studying the role of brain estradiol production and its potential to increase brain insulin activity in the brain could ultimately lead to new treatments for Alzheimer’s disease.

End of Award Update

Source: CLEAR Foundation

Dr. Mehran’s hypothesis was that estradiol produced by neurons enhances the production and action of insulin in the brain, and that this would have beneficial effects in a rat model of Alzheimer’s disease. However, even using some of the most sensitive assays, they failed to yield a difference.

However, Dr. Mehran discovered that second-generation antipsychotic medications inhibit insulin maturation. This finding is important because these medications are used to treat patients with psychosis and Alzheimer disease. These medications may be contributing to cognitive harm, by reducing levels of brain insulin.

Does Diesel Exhaust Exposure Alter Epigenetic Signatures in Individuals with Specific Allergies? A Translational Study to Understand the Role of Particulate Matter.

Asthma is a chronic lung disease affecting more than 2.8 million Canadians. It is estimated that numbers may rise to 400 million globally by 2025, substantially increasing both human and financial costs.

One possible explanation is that environmental exposures, including diesel exhaust (DE) air pollution (which usually increases as countries develop), may synergize with inhaled allergens in both the development and worsening of asthma, often leading to “lung attacks.” Exposure to air pollution may affect healthy gene expression in the lungs through “epigenetic modifications,” which change how cells “read” DNA. In preliminary studies, we confirmed that DE exposure caused numerous epigenetic changes, but we still need to understand how this causes the worsening of asthma symptoms. Moreover, we do not understand which components of DE (gases or particles) are driving these changes and which are more harmful. Therefore, I will leverage a state-of-the-art human exposure chamber and an ongoing clinical study to determine whether exposure to DE (with or without particles) and specific allergens affects epigenetics and gene expression.

Healthy and mild asthmatic volunteers will be recruited; over the course of four randomly-ordered visits (each separated by a month), they will be exposed for two hours to filtered air, DE, or particle-depleted DE, followed by inhalation of volunteer specific allergen or salt water. After 48 hours, cells lining the lungs will be collected and genetic material will be analysed.

Parallel to this clinical study, I will perform basic research experiments exposing lung cells to DE, and investigate the mechanisms through which these changes may occur. In addition, these experiments will examine how DE alters responses to asthma therapies and thereby the risk of “lung attacks.”

These studies may contribute biological plausibility and deepen our mechanistic understanding of emerging epidemiology, suggesting a role for air pollution in “lung attacks,” asthma development, and clinical outcomes.

Identifying and correcting for chronic circadian misalignment in Alzheimer’s disease

Alzheimer’s disease (AD) is the most common cause of dementia. Unfortunately, there are no effective treatments for this devastating disease. The Alzheimer’s Society estimates that without new treatments, 1.4 million Canadians will be living with dementia by 2031.

Patients with AD often experience disrupted circadian rhythms, manifested as disrupted sleep. Although largely attributed to the underlying disease process, recent findings suggest that sleep directly impacts the pathophysiology of AD. A promising, emerging hypothesis for identifying novel treatments is correcting for changes in the body’s internal time-keeping mechanism, the circadian system.

It is largely assumed that disrupted rhythms are caused by the dampening of central suprachiasmatic nucleus (SCN)-driven rhythms; however, bright light and melatonin treatments, which have putative action on central SCN-driven rhythms, have only had limited success improving cognitive and non-cognitive symptoms. Alternatively, AD pathology may be disrupting synchrony between central and peripheral rhythms, which would cause similar symptoms but require different interventions.

Peripheral rhythms control the timing of cellular and metabolic processes in organs (e.g. liver) and brain regions (e.g. hippocampus). Synchrony ensures that physiological processes throughout the body occur at optimal times. In contrast, desynchrony is extremely detrimental to health and affects the clearance and repair mechanisms necessary to combat the misfolded proteins driving pathogenesis.

The goal of my research is to identify the cause of circadian dysfunction and potential targets for interventions. First, I will characterize the circadian phenotype in a mouse model by measuring behavioural rhythms and sleep. Second, I will measure bioluminescence linked to circadian gene expression, as a real-time reporter of oscillators throughout the body and brain. This has never been done in an AD model and allows us to directly evaluate synchrony between oscillators. Third, I will evaluate whether the “hunger hormone” ghrelin, which directly affects circadian rhythms, neuroplasticity, and memory processes, can improve synchrony between oscillators. Finally, in AD patients I will characterize circadian dysfunction and sleep, and evaluate whether ghrelin can aid in restoring circadian synchrony. My project is the first to explore whether the peripheral circadian system can be modulated as a therapeutic intervention in AD.