Upcoming Research Grant Applications

The Manitoba Medical Service Foundation (MMSF) will consider the provision of funds for the advancement of scientific, educational, and other activities in the maintenance and improvement of the health of the residents of Manitoba.

The primary focus of the Foundation is to promote and encourage the work of new health researchers in Manitoba.
2023 Recipients Awards

The Manitoba Medical Service Foundation would like to congratulate the following successful recipients of the 2023 MMSF operating grant competition and wish them all success in their research.

Dr. Brenton Button

Exploring the impacts of extreme weather on children during the school day

Affiliations:
University of Winnipeg

Outdoor school recess is an important part of the school day. It gives children chances to be active, spend time outside and play with friends. These activities have been linked to improved health and well-being.

Due to school rules, approximately 30 per cent of recesses are modified to be indoors under certain weather conditions. During indoor recess, children have fewer chances to be active, play outside or play with friends.

This project aims to work with children to explore their thoughts and feelings of play in extreme weather and during indoor recess. Manitoba has some of the harshest winters in Canada. These findings can help change rules to give students chances to play and be active during indoor recess.

Dr. Catherine Card

Convergence of epidemics: The effects of methamphetamine use and concurrent STBBI on the immune system and HIV susceptibility

Affiliations:
University of Manitoba

There is a merging between the methamphetamine (meth) and HIV epidemics. Since 2018, more than half of new HIV infections in Manitoba have been among people who inject drugs (PWID), with meth as the leading substance injected.

People who inject drugs are more likely to have multiple infections transmitted by sexual contact or blood products (referred to as STBBI), and women tend to be more affected than men. Meth use and STBBI can have dramatic impacts on the immune system, with each independently leading to inflammation and increased susceptibility to other infections, including HIV. However, the combined effects of meth use and STBBIs on inflammation and immune system function in PWID are unclear.

This study aims to address these gaps in knowledge by measuring inflammation, immune cell activation and immune function in blood samples from PWID who use meth. We’ll also try to determine whether STBBIs further aggravate these immune outcomes.

We’ll also test the extent to which cells from the study participants are readily infected with HIV in the lab, to see whether the immune outcomes are related to HIV susceptibility. We will explore how biological sex and gender impact these effects in PWID.

This study will reveal important information regarding the immune health of PWID. It’ll help guide approaches to engaging them in STBBI prevention and harm reduction strategies that address their needs.

Dr. Sabrina Lee

Travelling for Abortion Care: A Critical Qualitative Analysis of Experiences Accessing Therapeutic Abortion in Winnipeg

Affiliations:
University of Manitoba

Despite Canada’s global leadership in reproductive rights, there remain significant barriers to accessing comprehensive abortion care due to inequitably distributed services, prohibitive costs due to loss of employment and travel, and lack of knowledge among providers and those seeking abortion services.

With the vast majority of abortion care involving a surgical procedure, comprehensive abortion services are concentrated in large cities along the southern border of Canada. The recent introduction of mifepristone (the gold standard in medication abortion) following Health Canada approval in 2015 and commercial availability in 2017 has transformed the Canadian abortion care landscape. This oral regimen offers the opportunity to improve the geographical inequities described in the literature when examining access to abortion services.

This qualitative study aims to provide insight into the experiences of those travelling to Winnipeg for both surgical and medical abortion care. We hypothesize that experiences of people travelling to Winnipeg for abortion care will similarly reflect logistical, emotional, and financial barriers associated with travelling for abortion care. Using Critical and Feminist lenses, we will conduct semi-structured interviews to achieve the following objectives:

  1. To explore the experiences of those travelling at least one hour by road or any travel-time by flight to Winnipeg for induced abortion services.
  2. To understand the process behind the choice of abortion method in those travelling at least one hour by road or by flight to Winnipeg for induced abortion services.
  3. To investigate perceptions and attitudes towards surgical and medical abortion among those travelling at least one hour by road or by flight to Winnipeg for induced abortion services.
  4. To provide insights into facilitators and barriers to accessing abortion services in those travelling at least one hour by road or any time by flight to Winnipeg for induced abortion, potentially identifying areas for improvement in abortion health policy and abortion service delivery.

This study will add unique insight to the young knowledge base in Canada of experiences in those needing to travel for their abortion care. Our results will have the potential to improve abortion services in rural and remote areas, improve our understanding of travel experiences for abortion care when necessary, and bolster provider knowledge in ways to better serve this particular population in the outlined circumstances.

Dr. Devin Lemmex

The impact of varying weightbearing restrictions on postoperative outcomes following arthroscopic surgery for femoroacetabular impingement: a randomized trial

Affiliations:
University of Manitoba

Femoroacetabular impingement is a condition of the hip that primarily causes pain in young and active individuals. It is caused by irregularities in the shape of the bones that make up the hip joint, leading to tears in the cartilage. It can eventually lead to arthritis.

To treat this condition, patients often undergo lengthy periods of physiotherapy, use anti-inflammatory medication and undergo injections into the joint. However, if these are not effective, then surgery may be performed.

This type of surgery is done through small incisions, using a camera, and is minimally invasive. The available studies evaluating this type of surgery tell us that it is safe, reproducible and very effective.

Despite technological advances and modern techniques used inside the operating room, it is unclear on how patients should start their rehabilitation process afterwards. Specifically, should they be using crutches to protect the hip from weightbearing, or should they begin walking as soon as possible? This is a simple question but one that potentially can make a big difference in early recovery and comfort after surgery.

This study aims to help answer that question by comparing patients placed into two separate groups and following their post-operative outcomes. We will also be evaluating our physiotherapy techniques to determine when a patient is fit to return to sports after this type of hip surgery.

Dr. Paul Marcogliese

Discerning neuroregressive ataxia and autism in two novel knock-in mouse models.

Affiliations:
University of Manitoba

Manitoba has a critical, unmet need to understand and treat developmental disorders, including autism spectrum disorder. We and others have identified different types of variants in the gene called IRF2BPL associated with both autism spectrum disorder and a highly severe neurological disorder that presents in children around the age of five years old called NEDAMSS.

Although variable, NEDAMSS patients have neurological regression including loss of speech, loss of developmental milestones, seizures, and movement abnormalities where they eventually become immobile in adolescence. Beyond being an important human disease gene, IRF2BPL is an interesting gene as it is enriched in the brain and mostly unstudied.

We and our collaborators have made models of IRF2BPL in fruit flies and zebrafish. However, there are no models in mice, which are needed for translating pre-clinical drug screening studies to patients. In this proposal, we have generated two patient-specific mouse lines associated with either autism or NEDAMSS. We will characterize both of these novel mouse models, determining if there are behavioural defects as well as pathology in the brain.

Moreover, we can use these two mouse lines to discern, mechanistically, why certain mutations lead to autism spectrum disorder and other mutations lead to a severe neurological disorder like NEDAMSS. Both models will deepen our understanding of neurodevelopment and neurodegeneration.

Neurodevelopmental disorders in Manitoba

Manitoba has some of the highest rates of neurodevelopmental disorders in Canada, having specific populations where novel gene variants have been identified. Moreover, autism spectrum disorder has seen an increased prevalence in Manitoba. Importantly, few if any of these neurodevelopmental disorders or autism spectrum disorders have approved therapies that can reverse or prevent them. Hence, there is a clear need for basic studies to both inform on pathogenic mechanisms and to develop pre-clinical models for therapeutic testing.

Dr. Inna Rabinovich-Nikitin

Circadian Dependent Cardiometabolic Heart Failure

Affiliations:
University of Manitoba

The circadian clock of the body controls the timing of key physiological processes. It’s influenced by environmental cues, like day and night cycles, as well as nutrient status. The past decade of research has led to a growing body of evidence that disruption of the circadian clock, such as that seen in shift workers, plays a critical role in the development of cardiometabolic syndrome (CMS).

CMS is defined as a set of metabolic abnormalities, including obesity, blood-lipid accumulation, insulin resistance and high blood-pressure. CMS leads to changes in heart structure and function, which increase the risk of heart failure, with higher prevalence in women. (In fact, heart disease is the leading cause of death in women and is responsible for one in every five female deaths, although more research needs to be done to learn why women are at greater risk).

Furthermore, increasing evidence has shown that disrupted circadian rhythms, such as seen in shift workers, is closely associated with increased risk for CMS and worse outcomes. Shift workers are common in the modern world, accounting for 30 per cent of the work force. Therefore, there is an immediate need to reveal the molecular link between circadian disruption and CMS and to understand its sex-dependent underlying mechanisms.

CMS is a growing public healthcare issue worldwide due to its increasing prevalence and its extensive influence on various age, gender and ethnic groups. Moreover, since those diagnosed with CMS ultimately develop heart failure for which there is no cure, CMS is considered a major socioeconomic burden to our health care system since it requires costly long-term care. This impacts the quality of life of the patient as well as their family members who must provide care.

Therefore, this proposal will investigate the link between circadian disruption and cardiometabolic heart failure, with the goal of minimizing heart disease. To do this, we’ll apply a “night shift-work model” on male and female CMS mice.

We’ll then examine a nutritional stimulation approach that involves modulating the expression of genes that control both circadian regulation and heart response during CMS.

We anticipate that this study will promote new therapeutic avenues that will improve the metabolic damage caused by circadian disruption. This research will contribute to the improved health of Canadians and lessen the burden on our health system.

Dr. Leslie Redmond

Development of a Culturally Appropriate Gestational Diabetes Mellitus Prevention Program for Urban-dwelling Indigenous Individuals in Manitoba

Affiliations:
University of Manitoba

This project will develop an intervention that will aim to decrease the risk of gestational diabetes mellitus, or GDM, in urban-dwelling Indigenous people in Manitoba.

GDM is a serious health condition that can put both the pregnant person and the baby at risk for complications, both during pregnancy and well into the future. Preventing GDM is especially important for Indigenous people, as prevalence is high and many other health disparities are also present.

Country foods (foods supplied by the land) and lifestyle activities have many health benefits, including the prevention of type 2 diabetes and GDM. However, country foods and lifestyle activities are less available and accessible to urban-dwelling Indigenous people in Canada, and those at risk for GDM may not be able to benefit from them.

This project will work with urban-dwelling Indigenous people and stakeholders committed to improving Indigenous health to develop a GDM risk-reduction intervention that focuses on country foods and lifestyle activities. We hope that this intervention will lead to improved personal health of urban-dwelling, pregnant Indigenous people and contribute to overall better population health through the prevention of health risks and complications in future generations.

Dr. Diana Sanchez-Ramierz

Effect of Pulmonary Telerehabilitation and Telemonitoring for patients with chronic respiratory diseases: a feasibility study.

Affiliations:
University of Manitoba

Pulmonary rehabilitation (PR) has shown great benefits in patients with chronic respiratory diseases. Unfortunately, this intervention is frequently inaccessible to patients.

Remote rehabilitation and monitoring of patient’s vital signs (e.g., heart rate) are potentially valuable mechanisms to improve patient care and access, especially in rural areas. However, further research is needed to assess the effect and practicality of delivering PR programs using telerehabilitation and telemonitoring.

This study aims to evaluate the effects of a pulmonary telerehabilitation program that incorporates telemonitoring on patients with chronic lung diseases. It also aims to assess the feasibility of using videoconference and commercial wearable devices in patient treatment.

In this study, 24 patients with chronic obstructive pulmonary disease and/or pulmonary fibrosis will participate in a pulmonary telerehabilitation program involving group exercise and education sessions via videoconference.

Heart rate, blood oxygen level and physical activity will be monitored using a smart watch and a finger pulse oximeter connected to a smart phone or tablet. We anticipate that people will experience improvement in their health outcomes and be satisfied with receiving the intervention in the comfort of their home.

Additionally, results of this study will guide the planning and development of alternative formats for PR programs in Manitoba, which could improve access to this much-needed service, especially for patients with mobility difficulties and patients who live outside Winnipeg.

Dr. Ayesha Saleem

Uptake of fetal extracellular vesicles (EVs) across placental barrier

Affiliations:
University of Manitoba

The process of cell-to-cell communication involves small bubbles of cellular material called extracellular vesicles (EVs), which are released from all cells.

Think of EVs as emails – just like an email can have text, video or audio files, EVs are versatile in the messages they can carry. EVs can hold different combinations of proteins, fatty acids and nucleic acids, and this cargo can change depending on the cell type of origin, physiological conditions, and the intended recipient cell.

Several studies have explored the mechanisms of EV synthesis and release and catalogued the variety of enclosed biochemical content.

Interestingly, EVs have been shown to cross physiological barriers, like the blood-brain barrier. If EVs can cross the (almost impenetrable) blood-brain barrier, it is likely that they can also cross the placental barrier. This makes them ideal candidates for mediating communication between fetus and mother.

This project will investigate whether EVs form the main biological communication link between mother and fetus. If fetal EVs can be detected in maternal blood/tissues, it will not only advance basic science knowledge, but also lead to the development of improved blood-based diagnostic markers that can be used to identify fetal abnormalities in a timely and safe manner. Early diagnosis may help prognosis and facilitate improved health outcomes for the unborn child.

Dr. Rene Zahedi

Improved prediction of subclinical and early clinical kidney transplant rejection by a CXCL10 isoform specific mass spectrometry assay

Affiliations:
Univeristy of Manitoba

More than 40,000 Canadians have end-stage kidney disease (ESKD). Approximately 60 per cent of these undergo dialysis. The cost of dialysis can reach $200,000 per patient per year in remote areas of Manitoba and amounts to over $2 billion per year in Canada.

Nevertheless, approximately 50 per cent of these patients typically die within four years. Kidney transplantation improves ESKD patient survival and quality of life and reduces costs. Unfortunately, one in three patients will experience transplant rejection within a year, leading to a considerably reduced survival rate.

Although early detection and early treatment can dramatically reduce the risk of rejection and death, current clinical testing fails to detect rejection early enough. Therefore, we are investigating whether a specific molecule in urine, the protein CXCL10, enables early detection of rejection and can predict outcomes.

CXCL10 urine levels are clearly higher in patients with transplant rejection, allowing not only early detection but also personalized treatment. However, predictions made based on the currently available testing method are often not accurate. A probable reason is that these tests cannot distinguish between different forms of the CXLC10 protein. Although these different forms are almost identical, they have very different effects – some of them may accelerate rejection, while others may slow it down.

We will develop a more specific test to clearly distinguish these different forms of urinary CXCL10 and thus improve its diagnostic value for transplant patients. Ultimately, this will enable more personalized patient treatment to yield better outcomes, higher survival rates and a better quality of life, while reducing costs.

2022 Recipients Awards

The Manitoba Medical Service Foundation would like to congratulate the following successful recipients of the 2022 MMSF operating grant competition and wish them all success in their research.

Dr. Heather Armstrong MSc, PhD

Defining the role of the intestinal microbiome in the regulation of dietary fibre-associated inflammation in Inflammatory Bowel Disease patients

Humans do not digest dietary fibres – instead, they are broken down (fermented) by gut microbes (bacteria and yeast), typically promoting health. However, inflammatory bowel disease (IBD) patients can experience worsening symptoms after eating fibres for unknown reasons. Our previous work assessed several different fibres (e.g., β-fructans) and showed that whole, unfermented β-fructans can promote gut damage in specific IBD patients. This negative response was the result of a loss of patient gut microbe’s ability to break down β-fructan, more common in patients with active disease.

We believe that promoting growth of healthy gut microbes and their ability to ferment β-fructans will inhibit fibre-associated progression of IBD.

In this study we aim to:

1) Identify how the human cells are involved in inflammation and cancer-promoting response to dietary β-fructans using cells in the lab and IBD patient biopsies cultured in the laboratory

2) Uncover the precise role of the previously identified microbial factors in regulating host response to associated β-fructans by stimulating and/or inhibiting these predictive microbial factors and measuring outcomes

3) Validate biomarkers or response to β-fructans in our readily available clinical biological specimens (stool, serum, biopsies).

Use of β-fructans is largely touted to provide benefits to healthy individuals and some persons with IBD in remission. However, our work is the first to demonstrate some patients experience negative effects of fibres. Understanding how this happens would allow us to develop more safe, readily available, and affordable dietary interventions and microbe-altering therapeutics to reduce disease burden in patients with dietary-fibre sensitivities.

Panel Writeup

The impact of inflammatory bowel disease

Inflammatory bowel disease consists of two diseases – Crohn's disease and ulcerative colitis. Symptoms include abdominal pain and cramping, diarrhea, bloody stool, rectal bleeding and nausea and vomiting.

Canada has among the highest incidence rates of Crohn's and colitis in the world – 300,000 people across the country, according to Crohn’s and Colitis Canada. The direct annual cost of caring for Canadians with IBD is estimated at $1.28 billion.

The prevalence of Crohn’s and colitis in Canadian children has risen more than 50% in the last 10 years. Children with Crohn’s or colitis have different disease complications, respond differently to treatments, and are at a greater risk of side effects of medication as compared to adults.

Research shows that the probability of a person developing colorectal cancer after having Crohn’s or colitis for 10 years is 2%. After that, risk continues to rise and is as high as 30% after 30 years. In other words, as age increases, so does risk.

Dr. Robin da Silva, BSc, PhD

The Role of Adenosine Receptors in Fibrosis

Fibrosis arises when dying tissues are replaced by connective proteins during tissue repair. The immune system plays an important role in the removal of connective proteins during repair and maintenance of tissues in the body. Malfunction or death of immune cells can result in accumulation of connective proteins that leads to fibrosis. Many diseases, including cancers, diabetes and others involving tissue fibrosis are caused or made worse by either malfunction or death of immune cells. Unfortunately, there are currently no effective treatments for tissue fibrosis.

The past few decades have brought great advances to our understanding of the immune system. However, despite these advances, much is still unknown about how immune cells communicate and perform their operations. The goal of this study is to further our understanding of how adenosine receptors are involved in immune cell communication in particular signals that result control the activation and death of immune cells. We will use molecular technique and bioinformatics to discover new pathways through which immune cells communicate and function. The findings from this study will provide new avenues that will allow us to manipulate immune cells to better manage and potentially cure tissue fibrosis.

Panel Writeup

The impact of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)

The prevalence of NAFLD is estimated to be 30 per cent of adults in Canada. Approximately 15 to 20 per cent of patients with NAFLD progress to more serious liver disease that includes fibrosis called non-alcoholic steatohepatitis (NASH). NASH fibrosis arises when dying tissues are replaced by connective proteins during tissue repair. Unfortunately, there are currently no effective treatments for liver fibrosis and 6800 Canadians develop liver failure each year. Current modelling estimates that the number of deaths attributed to NASH will double in ten years.

Dr. Tomislav Jelic, MD, FRCPC

Accelerated Remote Consultation Tele-POCUS in Cardiopulmonary Assessment (ARCTICA)

Point-of-Care ultrasound (POCUS) is the use of ultrasound imaging devices at the bedside of patients. It provides a quick and accurate picture of the heart and lungs. Common clinical use includes the assessment of shortness of breath to determine whether the cause is heart- or lung-related.

While POCUS devices are now widely available, not all providers have the training and expertise to conduct POCUS. The Goal of ARCTICA is to create a Tele-POCUS training program and consultation service for providers who currently do not use POCUS in their practice.

The program will begin at St. Boniface and Health Sciences Centre, where physicians will be taught using a novel technologic platform incorporating augmented reality to learn new POCUS skills. To continue their learning and ensure they are making accurate diagnoses, experts in heart and lung ultrasound will give live video consultations to these physicians through a secure video call app. These video consultations will allow the heart and lung ultrasound experts to guide physicians as they diagnose patients directly at the bedside.

Panel Writeup

The benefits of POCUS

The ability of a remote health care provider to use point of care ultrasound safely after ARCTICA training to rapidly assess, diagnose and initiate management that could lead to improved patient care and clinical outcomes, all while receiving real-time oversight from POCUS experts. ARCTICA could also allow for the triage of who may need medical evacuation from a remote or rural community for more advanced diagnostics or who could be kept in their home community for medical management. The socioeconomic impact of this is thought to be positive and will be assessed in phase two and three of ARCTICA.

Dr. Cara Katz, MD, FRCPC

Sibling Outcomes among probands with Autism Spectrum Disorder: A Population-wide Longitudinal Cohort Study

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder where people may have difficulty with social communication and interaction as well as restricted and repetitive patterns of behaviour, interests or activities.

On top of its effects on the patient, ASD comes with unique challenges for family members. Getting professional help for these neurodevelopmental disorders can be difficult and there are long wait times. Therefore, the ability to target interventions to whole families or other individuals within a family at risk of poor outcomes is important.

Previous literature has found increased mental disorders in siblings, but other areas of functioning, including physical health, injuries, medication use, and education remain unexplored. Using provincial health data, we will examine the impact over time of a sibling with ASD on the mental and physical health and education outcomes in other siblings. We will gain knowledge on which siblings are at greater risk and therefore identify potential targets for including family and sibling interventions within resource-strained neurodevelopmental programs.

With the onset of many mental disorders in youth, this is a critical time to be able to alter illness trajectories to help prevent onset of negative outcomes. This is the first study to examine the impact of an ASD individual on the educational outcomes of siblings, which can help identify important time points for intervention and an additional avenue for identifying sibling needs outside of the healthcare system.

Panel Writeup

The impact of autism spectrum disorder in Canada

Autism Spectrum Disorder is a common neurodevelopmental disorder with a modest prevalence estimate of one per cent of the population, affecting males more than females. Around one in 66 Canadian children between age five and 17 have been diagnosed with autism spectrum disorder, including one in 42 boys and one in 165 girls.

It has been estimated that up to 37 per cent of siblings of those with Autism Spectrum Disorder are diagnosed with a psychiatric or neurodevelopmental disorder.

Dr. Maia Kredentser, C.Psych

One-year cognitive and mental health outcomes in hospitalized COVID-19 survivors

After being hospitalized with COVID-19, many people experience difficulties with their emotions – things like mood, worries/tension, difficulty sleeping. Many also have problems with how their brain works – things like thinking clearly, planning, and paying attention. Their family members may also feel very stressed and overwhelmed.

These difficulties can last many months and make it difficult to get back to normal life. This study will examine in detail these difficulties for patients and their family members one year after the patient was discharged from the hospital. Patients and family members will complete a psychological assessment that includes patients completing tasks that measure how they plan, think, pay attention and organize. Patients and their family members will also answer questions about their emotions and symptoms they may have.

We have information about these patients and family members from the time they were in the hospital one year ago until now, and we will therefore be able to examine how aspects of their illness, emotional and brain functioning are impacting their current symptoms.

Patients and their family members will also be asked about their experiences with COVID-19 illness, being in the hospital, how their recovery has been, and what they think would be helpful to support them in the recovery process. The findings from this study will help us understand what kinds of healthcare, information and support people need after they have been hospitalized with COVID-19. We will share these findings with other researchers and health care providers/organizations caring for people recovering from COVID-19.

Panel Writeup

The long-term impact of COVID-19

A summary of the literature so far on the long-term effects of COVID-19 (sourced from UpToDate):

- “Psychological and cognitive complaints are also common during recovery from acute COVID-19 and may be seen more commonly than in those recovering from similar illnesses (e.g.,Carfi et al 2020, Xiong et al, 2021, Taquet et al, 2021a). In one study of 100 patients with acute COVID-19 who were discharged from the hospital, 24 percent reported PTSD, 18 percent had new or worsened problems with memory, and 16 percent had new or worsened problems with concentration; numbers were higher among patients admitted to the intensive care unit (ICU) (Halpin et al, 2021). In other studies, almost one-half of COVID-19 survivors reported a worsened quality of life (Carfi et al, 2021, Wong et al 2020), 22 percent had anxiety/depression (Wong et al 2021), and 23 percent of patients were found to have persistent psychological symptoms at three months (Xiong et al, 2021). Among ICU survivors, another study reported anxiety in 23 percent, depression in 18 percent, and posttraumatic symptoms in 7 percent (Writing Committee for the COMEBAC Study Group, 2021).”

- “…a retrospective examination of electronic health records in the United States reported that the risk of developing a new psychiatric illness following COVID-19 was higher compared with those recovering from other medical illnesses such as influenza (Taquet et al, 2021b).”

- “…Persistent symptoms can affect functional ability. As examples: In one retrospective study of approximately 1300 hospitalized COVID-19 patients discharged to home, despite home health services, only 40 percent of patients were independent in all activities of daily living (ADLs) at 30 days (Bowles et al, 2021). In another study, almost 40 percent of patients were unable to return to normal activities at 60 days following hospital discharge (Chopra et al, 2021). In another study of 219 patients who were hospitalized with COVID-19, 53 percent had limited functional impairment (as measured by the Short Physical Performance Battery [SPPB] score and two-minute walking test) at four months (Bellan et al, 2021).”

Dr. Shuangbo Liu, MD, FRCPC

Dial Don’t Drive – a Manitoba Acute Coronary Syndrome Network public awareness campaign to reduce patient delays in seeking medical attention for heart attacks and their caregivers

The goal of the Manitoba Acute Coronary Syndrome (ACS) Network’s “Dial Don’t Drive” project is to decrease delays for patients with chest pain and potential heart attack to receive medical care. The key message of “Dial Don’t Drive” emphasizes the importance of calling 911 instead of driving oneself to the doctor or the emergency department, and education about the typical and atypical symptoms of a heart attack. This includes not only chest pain, but shortness of breath, excessive sweating, nausea or heartburn.

The Dial Don’t Drive project will harness the power of social media for this mass media campaign through Facebook, Instagram and promotional material.

The elements of this multi-phased social media campaign include:

- Team STEMI (showcasing health care professionals that a patient may meet when having a heart attack)

- Patient Voices (describing patient journeys and experiences)

- Education (focusing on patient education)

- Ask Me Anything (interactive question and answer)

- Seasonal (leveraging existing networks to celebrate key dates)

The DDD study objectives are to:

- decrease patient-related delays in seeking care for chest pain syndrome

- increase the proportion of patients calling 911 for chest pain syndromes instead of presenting to the emergency department

- improve clinical outcomes such as death, less heart damage and heart failure

The effects of the DDD project will be immediate and impactful – leading to patient benefits as well as the improved efficiency and cost-savings for Manitoba’s healthcare system. Since heart attack patients will present sooner and receive appropriate treatment faster, they are less likely to have long-term complications or require complex cardiac care.

Panel Writeup

Heart attacks and emergency treatment

Only around half of Manitobans call 911 when having a heart attack – and one in 18 Manitobans who drive themselves to the hospital during an attack will die. For every hour treatment is delayed, the chance of severe damage or death rises 10 per cent. People who call 911 instead of driving themselves to the hospital are diagnosed with heart attacks three times faster.

Dr. Marc Morissette, MSc, PhD

Evaluating the effectiveness of an electronic data collection platform to improve patient response rates in an orthopaedic surgery registry

Increasing patient involvement is becoming standard practice across healthcare in Canada, with the collection of patient-reported outcome measures (PROMs) serving as a common way to enhance patient-physician interactions and measure value of treatment from a patient-perspective.

Traditional PROMs collection involves the distribution of paper forms, resulting in low return rates, increased patient burden and missing data. This suggests that supplemental or alternative methods of PROMs collection are warranted. Interestingly, digital platforms allowing for the collection of electronic PROMs (ePROMs) have been shown to increase patient response rates in an orthopedic setting; however, findings are limited to patients receiving total joint replacements, they involve digital platforms not available in Canada, and they benefit greatly from additional staff (albeit at additional financial costs).

Our research proposal seeks to:

- compare response rates between paper-based PROMs and ePROMs for anterior cruciate ligament reconstruction (ACL-R), rotator cuff repair (RCR), and shoulder stabilization surgery pre-operatively and at three-weeks – with three- and six-month follow-up time points

- assess the impact of staff-facilitated ePROMs data collection.

The results from our study will inform various levels of healthcare, including at the patient/institutional, provincial, and national levels. Various divisions of healthcare are moving towards a patient-centric culture of care to ensure patients remain involved throughout treatment and rehabilitation. Given the lack of uniform PROMs collection prior to and following sports medicine orthopedic surgery, our study will provide novel evidence in support of ePROMs collection for ACL-R, RCR, and shoulder stabilization surgery that can be adopted across Manitoba and Canada.

Dr. Natalie Richer, PhD

The impact of attentional focus on postural stability in the aging brain

Aging is an inevitable outcome of life that, eventually, is accompanied by declines in health and body functionality. One main result of these changes is a loss of balance that leads to an increased rate of falls. Many experiments have attempted to understand age-related changes in postural control. Recent advances in mobile brain imaging introduce a new possibility: to examine the neural control of balance and how it changes with age.

When we stand or walk, our minds usually aren’t idle. We focus our attention on a secondary task, such as a conversation, or we focus on various thoughts. My previous research suggests that what we place our focus on can influence our stability. I found that focusing attention away from the task of standing can improve stability in healthy young and older individuals.

My objective is to examine the effect that attentional focus has on postural control while examining brain activity to gain a better understanding of underlying processes and how they change with advancing age. I will use electroencephalography (EEG) to examine brain activity during quiet standing while changing the focus of attention in young and older adults.

This project will reveal new information about which brain structures contribute to reduced balance performance in older adults. The results will later be used to find ways to improve balance and reduce the risk of falls in this population.

Panel Writeup

Canada’s aging population

Approximately 30 per cent of older adults over 65 years of age fall every year, and this proportion increases with age. These falls are a leading cause of injury-related hospitalization in this group.

The Government of Canada predicted that by 2030, 23 per cent of Canadians will be 65 years of age or older, compared to 15.6 per cent in 2014. This demographic shift increases the importance of understanding age-related declines in motor behavior and finding and implementing ways to delay these changes.

Dr. Barret Rush, MD, MPH, FRCPC

One-year cognitive and mental health outcomes in hospitalized COVID-19 survivors

The care of critically ill people in Intensive Care Units is a large and expensive part of health care. Each year, over two per cent of older Manitobans experience a critical illness.

Twenty per cent of Canadians live in rural areas. Compared to urban residents, they are thought to face additional barriers to obtaining health care and to have worse outcomes from illness. Such problems are likely even greater for those with critical illnesses. But little is actually known about rural versus urban disparities in care of critically ill people.

We will use data at the Manitoba Centre for Health Policy to study how living in rural Manitoba impacts access to care and clinical outcomes for patients with one of two important types of critical illness – COVID-19 pneumonia, and sepsis, which is organ failure due to infection (a common type of critical illness).

We hypothesize that rural residents will have higher rates of hospital admission, but lower rates of ICU admission due to lack of ICU care in rural areas. For patients who make it to the ICU, we anticipate that the rural residents will have higher mortality.

This work is important, because before those who make health care policy decisions can work to remove the disparities, they first need to understand them.

Dr. Chrysi Stavropoulou, DDS

Elucidating the role of oral microbes and their metabolites in peri-implant health

Caused by mouth microbes, gum diseases are very common. They can present around teeth and dental implants, and they result in tooth/implant loss at the final stage.

So far, the cause of gum disease around implants is not fully understood. Also, little is known about the role of mouth bacteria and especially fungi around implants. The immune response could also play a role in the development of these diseases around implants.

Our goal is to identify mouth microbes (bacteria and fungi) that are important in gum heath. We also want to understand how bacteria and fungi talking to each other influence inflammation of the gums around implants. Saliva, dental plaque, and gum fluid will be collected once from people with healthy implants and people with diseased implants.

The plaque samples will be processed to isolate microbial DNA. The saliva samples will be analyzed for microbes’ by-products. Analysis of the gum fluid will show the role of immune response in gum disease around implants. Results from this study could assist in planning individual prevention or treatment options for gum disease around implants.

Panel Writeup

The impact of peri-implant diseases

Peri-implant disease, also known as gum disease around dental implants, is characterized by infection and inflammation of the tissues surrounding the implants.

In the early stages – referred to as peri-implant mucositis – the gums around the implant are red, swollen and bleed easily. The prevalence of peri-implant mucositis among people with dental implants is estimated to be 46 per cent. The disease is fully treatable in the early stages.

In later stages – called peri-implantitis – the gums around the implant recede and the bone is reduced or completely lost. If left untreated, the implant can become loose and fall off. Twenty per cent of people with dental implants develop peri-implantitis. Treatment can be challenging and removal of the implant often the best option.

With more than five million people receiving dental implant treatment in North America, peri-implant disease is of major interest in modern dentistry.

Dr. Rodrigo Villar, PhD

Autonomic cardiovascular, and respiratory regulation during postural transitions and acute and chronic exercise in females and males living with frailty

This research aims to:

- determine how frailty and sex impact the brain, heart, vessels, and lungs regulation

- determine how exercise can reverse frailty in older adults.

In study one, participants will perform three postural transitions:

- sit-to-stand

- lie-to-stand

- lie-to-sit

Participants will also perform three identical constant workload walking tests.

The autonomic (brain, e.g., sympathetic and parasympathetic activity), cardiovascular (e.g., heart rate, blood pressure, cardiac output), and respiratory (e.g., oxygen consumption, carbon dioxide output, ventilation) functions will be assessed in females and males with different frailty statuses.

In study two, frail individuals will perform 15 weeks of progressive strength or aerobic training to determine how exercise can reverse frailty and improve autonomic, cardiovascular, and respiratory function.

Homeostatic dysregulation compromises rapid adjustments in the autonomic, cardiovascular, and respiratory regulatory mechanisms affecting maintenance of homeostasis, especially in vulnerable populations (e.g., older adults). The dysregulation exposes them to higher risks of frailty, chronic diseases, and falls.

Frailty is characterized by the degradation of biological and functional reserves to tolerate stressors, resulting in high vulnerability to adverse health outcomes. People living with frailty are under-recognized, under-served, under-appreciated, and poorly understood. This research proposal is critical because it will inform the future development of more robust early frailty risk detection assessments, frailty preventative, and rehabilitative treatment/intervention strategies considering sex differences. Advancements in the fundamental knowledge of the underlying mechanisms regulating autonomic, cardiovascular, and respiratory responses will inform how to promote health, well-being, and quality of life for females and males living with frailty.

Panel Writeup

The impact of frailty

According to the Canadian Frailty Network, the burden of frailty in Canada is steadily growing. Today over 1.6 million Canadians are medically frail. And in 10 years, well over two million Canadians may be living with frailty. There are 3.75 million caregivers in Canada caring for an older adult (aged 65 and over) with a long-term health problem, disability or age-related condition.

Frailty is also linked to higher consumption of healthcare resources. Of the $220 billion spent on healthcare annually in Canada (11 per cent of GDP), 46 per cent is spent on people over 65 years old, although they are only 16 per cent of the population. The operating costs to care for the seven per cent of Canadians over the age of 65 that are living in long term care homes is $31 billion dollars.

Dr. Evan Wiens, MD, BA, MSc, FRCPC

Real-world Efficacy and Safety of Dual Antiplatelet Therapy with Ticagrelor as Compared to Clopidogrel

People that suffer a heart attack need emergency treatment to improve blood flow, treat complications and prevent future problems. To prevent future blood clots, patients are prescribed dual antiplatelet therapy. One of those medications is aspirin. The second type is a type of antiplatelet agent called P2Y12 inhibitors.

There are 3 P2Y12 inhibitors: clopidogrel, prasugrel and ticagrelor. Some studies have shown that ticagrelor is “stronger” than clopidogrel and a little better at decreasing complications of blood clots. However, ticagrelor can slightly increase bleeding. Our study aims to determine which type of P2Y12 inhibitors has the lowest risk of blot clots and death.

For our study, we will look at historical health records in Manitoba. We will look at every person who suffered a heart attack and who has been prescribed ticagrelor or clopidogrel and check whether they died or had to go to the hospital because of blood clots. From there, we will see if there are differences in those outcomes between the two types of medications. Patients are not identified to protect their privacy, but we can link records of prescriptions, hospital visits, and emergency department visits to a unique person.

We will share our findings with doctors and patients so we can help improve patient quality of life. Additionally, our findings have the potential to help the healthcare system be more efficient by lowering the number of times people need to go to the hospital or emergency room because of a blood clot event.

Panel Writeup

The burden of cardiovascular disease in Canada

A heart attack occurs when the flow of blood to the heart is blocked. A heart attack, also called a myocardial infarction, can be fatal, but treatment has improved dramatically over the years. Chest pain or discomfort is the most common symptom of a heart attack in both men and women.

Cardiovascular disease (CVD) has a large impact on the health of Canadians. Heart disease is the second leading cause of death in Canada. According to the Canadian Chronic Disease Surveillance System (CCDSS) about one in 12 Canadian adults aged 20 and over live with diagnosed heart disease. The prevalence of diagnosed heart disease increases as people age and is higher among men than women in all age groups. Cardiovascular disease contributes as much as $22.2 billion to health care costs each year.

Most Canadians have at least one risk factor for CVD. Reducing risk factors before the first heart attack or stroke can prevent or postpone 33 per cent of all deaths. A large percentage of the population is at risk of developing CVD or experiencing a second heart attack, stroke, or other CVD-related crisis. Treatment options for heart attack include lifestyle management, medications, and procedures such as percutaneous coronary intervention or coronary artery bypass graft surgery. Both primary and secondary prevention efforts must attain priority to decrease the incidence of fatal and non-fatal heart disease in the population.

Dr. Sanoji Wijenayake, PhD

Maternal Milk is more than food: Milk contains bioactive components that shape offspring neurodevelopment.

Maternal obesity is a major public health problem. In the United States, more than 50 per cent of pregnant women are obese at the time of conception; the comparable percentage is 22-24 per cent for Canadian women. This means that a high percentage of infants born in North America are exposed to an overweight and/or obese gestational environment and to maternal over-nutrition during lactation.

Previous research established strong associations between maternal obesity and adverse metabolic conditions (e.g., type II diabetes), alternations in growth and development where obese parents tend to produce obese children, and variations in neurological development (autism spectrum disorders and increased anxiety-like behaviors) in female and male offspring.

Breastfeeding is proposed as a solution to combat the risks of overweight/obesity in children. However, very little is known about the underlying biological mechanisms that confer this protective effect and how maternal obesity may affect the function of the bioactive compounds in breastmilk, especially the small, fat-coated vesicles known as milk exosomes that carry genetic information from mothers to their offspring.

My main objective is to characterize the role of milk exosomes as a functional regulator of early development and to characterize the cellular underpinnings of milk exosome transfer/localization. Mechanistic insights obtained from this research can be used to improve nutritional benefits of donor and formula feeding in neonates, where milk exosome-based signaling may be absent. Moreover, enrichment of formula with bioengineered milk exosomes could be used to treat a variety of metabolic syndromes and developmental complications that are associated with obesity.

2021 Recipients Awards

The Manitoba Medical Service Foundation would like to congratulate the following successful recipients of the 2021 MMSF operating grant competition and wish them all success in their research.

Dr. Alex Aregbesola

Improving Emergency Care for Children and Adolescents in Rural and Remote Manitoba

Around a third of all general emergency department (ED) visits in Canada are from children. However, these children are vulnerable to receiving care based on adult methods of treatment each time they visit an ED. This puts their lives at risk.

In Manitoba, there is only one children’s hospital that has an ED designed to treat children. Therefore, we expect many more ED visits from children at other hospitals for years to come. Additionally, death in younger children is about two to four times higher in Indigenous and other underserved populations.

To reduce the risk of mismanagement of children in EDs, we want to know the present state of EDs to care for injured and acutely ill children. We will study six main aspects:

1. Coordination of patient care

2. Staffing and training

3. Quality improvement

4. Patient safety

5. Policies and procedures

6. Availability of pediatric equipment/supplies

We want to know why EDs may not be able to give proper care for kids who need emergency treatment. We want to implement the same readiness initiative used in the United States, which was found to reduce child deaths in EDs.

To accomplish our goal, we will provide an online/PDF survey to all EDs to collect the information that we need for assessment. We’ll then conduct a study to implement readiness initiative in EDs. This study has the potential to help improve the emergency care of children in Manitoba.

Dr. Aleeza Gerstein

Variation in Vulvovaginal Candidiasis Drug Response: A Manitoba Cohort Study

Vulvovaginal candidiasis (VVC, commonly known as a yeast infection) affects a majority of women at least once in their life. Up to 10 per cent of afflicted women experience recurrent infections, for which there is no cure.

Chronic conditions that affect women are severely understudied, yet they can be incredibly detrimental to quality of life. About half of the women with recurring VCC have no identifiable risk factors, and there are few treatment options.

The fungal pathogen Candida albicans is the most prevalent species that causes VVC, yet other species and co-species infections are increasingly seen as well. Before and after treatment, we will use state-of-the art technology to characterize the genetics and drug responses of the infecting fungal population and the composition of the microbiome (i.e., the bacteria that are in the vagina during infection).

We will enroll two groups of women with VVC infections in Manitoba. The first group will contain women who have their first suspected VVC infection – they’ll be treated with fluconazole, the most common VVC drug. The second group will consist of women who have previously had infections that recurred on fluconazole, who will be treated with boric acid.

By looking for similarities and differences among the responses of these two groups of women, our results will help us to better understand how VVC infections respond similarly or differently to alternative treatments or infection types. In the long term, we aim to identify novel or personalized treatment strategies for this physically burdensome and costly condition that currently has no cure.

Dr. Biniam Kidane

Organ-Preserving Endoscopic Resection and Adjuvant RADIOchemotherapy for esophageal cancer (OPERA RADIO)

Removing the esophagus is the standard way to cure esophageal cancers. However, these risky surgeries can result in eating difficulties, pain, complications and even death. One in 10 people die in the first 90 days after surgery.

Cancers that have travelled only into the first layer of the esophagus can be cored out and removed through the mouth using a scope without surgery. This is called ESD/EMR. This is much less risky and less painful and doesn’t cause any eating difficulties.

If the cancer has spread into the second or third layers of the esophagus, most doctors believe that the riskier surgery is needed to get a better result. But some people don’t want or can’t handle these surgeries.

Prior to studies like this, the treatment of other cancers (e.g. breast cancer) used to only involve intensive surgeries. Today, doctors use combination therapies, like the ones we are proposing, successfully.

Our study aims to see if it is possible and safe to treat these people with cancers of the second or third layers using ESD/EMR followed by chemotherapy and radiation. Sometimes, patients who can’t handle or don’t want a riskier surgery get ESD/EMR or just get chemotherapy and radiation.

We think that combining these three treatments will give people a better chance at a cure while still being safer than a high-risk surgery.

Dr. Hagar Labouta

Tracking the Accumulation of Gold Nanoparticles in Tumour Tissues

Cancer is a leading cause of death in Manitoba, Canada and throughout the world. While considerable advances have been made in the treatment of different cancers, patients still suffer many side effects from current treatments.

The use of nanoparticles (ultra-fine particles in the nanometer scale) as drug carriers to treat cancer has shown promising results in targeting cancer tissue, resulting in better anti-cancer effects and fewer unwanted side effects in other parts of the body.

To enable the clinical translation of many of these nanoparticles, more work is needed to understand their behaviour in the body – especially their ability to penetrate deep into the cancer tissue to kill the cancer cells more efficiently.

We will design different nanoparticles that vary in size and surface properties, and we’ll test their ability to effectively penetrate cancer tissues under conditions similar to real-world scenarios.

This project will inform us about the best nanoparticle designs for penetration into cancer tissues. These nanoparticles will be used in follow-up animal experiments, and they will likely be used to treat patients in the clinic. In the future, successful nanoparticle designs will more effectively cure cancer patients and improve patient outcomes.

Dr. Deepak Louis

Mental Health Outcomes of Parents of Children Born Preterm in Manitoba: A Population-Based Cohort Study

Premature babies are babies that are born four or more weeks before their expected birthday. In Manitoba, approximately 1400 babies are born prematurely every year. These babies are often sick after birth, for which they require admission to hospital and ongoing medical support.

They are also likely to develop health complications while in hospital and can face delays in their growth and development after discharge. Thus, having a premature baby can be very stressful and anxiety-provoking for parents.

Prolonged exposure to stress and anxiety after having a premature baby has the potential to cause mental illness among these parents. However, we currently know very little about their mental health. It is vital to recognize poor mental health, as it can negatively affect parents’ physical health and relationships and impair their children’s growth and development.

In this project, we aim to determine how prevalent mental health conditions (like depression and anxiety) are among parents of premature infants. We will use routinely collected anonymized data from the Province of Manitoba to study their mental health outcomes. The information obtained from this study will help health care professionals, policymakers and organizations to plan and provide appropriate mental health support to these parents.

Impaired mental health is a growing concern for Manitobans, and we believe this research will help improve mental health outcomes.

Dr. Sapna Oberoi

Mental Health Outcomes of Adolescents and Young Adults with Cancer in Manitoba: A Population-Based Matched Cohort Study

Facing a cancer diagnosis is harder for adolescents and young adults (AYAs) than other patients. The diagnosis of cancer profoundly affects their independence, self-identity, fertility, sexuality and relationships. Many AYAs cannot continue with school, work or achieve their career goals due to the cancer diagnosis. As a result, these patients are at risk for depression, anxiety, substance misuse and  suicide.

Little is known about how common these mental health issues are among AYAs with cancer. We also don’t know which AYAs with cancer are at higher risk of developing these mental health issues.

Mental health is equally important as physical health and can affect all domains of life. In this project, we will measure how common anxiety, depression, substance misuse and suicide attempts are in AYAs with cancer during the first five years of cancer diagnosis in Manitoba. We will also find out which AYAs with cancer are at higher risk of developing these mental health issues.

Previously collected health data in Manitoba will be used for this study. The information from this study will help healthcare providers, cancer organizations, and policymakers create much-needed supports for AYAs with cancer. The extra mental health support will improve the overall health of AYAs with cancer in Manitoba.

Dr. Liam O'Neil

Searching for Citrulline: A Comprehensive Analysis of the Citrullinome Across the Stages of Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is common. In people who have RA, the immune system attacks joints in the body. This results in pain and movement problems for patients, and it reduces their ability to function. About one in 100 people develop this disease in their lifetime. Indigenous people are more likely to develop RA.

Unfortunately, researchers don’t understand why people develop this very common and serious disease. People with RA develop markers in their blood called antibodies. Antibodies usually fight bacteria and viruses. However, in RA these antibodies are directed against a portion of a protein called citrulline.

We already know that the amount of citrullinated proteins is different in patients with RA compared to healthy people without RA. We suspect that the inflammation that occurs in RA may be triggered by citrullinated proteins. Also, we think that these differences in citrullination are likely to occur before the development of the disease.

Our research team wants to learn which citrullinated proteins are higher in people with RA. We also want to find out which citrullinated proteins are higher when individuals with RA start to develop their antibodies. This will help us discover new markers in the blood that will help find people who are at highest risk to develop RA. This will help future researchers develop treatments that prevents citrullination from happening, which may stop arthritis from developing in the first place.

Dr. Zachary Raizman

Comparing the Effects of Long Acting Versus Intermediate Acting Versus Short Acting Insulins on Severe Hypoglycemia in Type 2 Diabetes

People with type 2 diabetes are sometimes prescribed insulin to help lower their blood sugar. Often, insulin will lower blood sugar too much, which can cause people to go to the hospital or the emergency room because of serious side effects. This can sometimes lead to death.

Insulin can be short acting, intermediate acting, long acting, or pre-mixed and each type of insulin may have a different risk of dangerously low blood sugar. Our study aims to determine which type of insulin treatment has the lowest risk of dangerously low blood sugar and death.

To do this, we will look at historical health records in Manitoba. We will look at every person with type 2 diabetes who has been prescribed insulin and check whether they died or had to go to the hospital or emergency room because of dangerously low blood sugar. From there, we will see if there are differences in those outcomes between different types of insulin.

Patients are not identified to protect their privacy, but we can link records of prescriptions, hospital visits, and emergency department visits to a unique person.

We will share our findings with doctors and patients so we can help improve patient quality of life. Additionally, our findings have the potential to help the healthcare system be more efficient by lowering the number of times people need to go to the hospital or emergency room because of a low blood sugar event.

Dr. Christiaan Righolt

Infant Vaccination Rates During the COVID-19 Pandemic in Manitoba

Physical distancing restrictions introduced as part of the response against the COVID-19 pandemic have limited access to medical services. Early reports suggest that childhood vaccination rates are lower during these restrictions. Infants that miss or delay their vaccines are at increased risk of vaccine-preventable diseases (such as measles and polio) and the reduced herd immunity can lead to new outbreaks of these diseases.

We need to know how many infants missed their vaccines, so we can plan for catch-up programs and minimize effects of future COVID-19 waves and vaccine-preventable disease outbreaks.

We will examine this by comparing infant vaccinations before and during the pandemic. We will measure the drop in vaccinations, both for all vaccines combined as well as for individual vaccines (e.g. the measles vaccine). We will determine whether these infants catch up on missed vaccines in the short term (within six months) to minimize their risk.

This information will help build the response to COVID-19 and prevent further harm from the pandemic.

Dr. Tanveer Sharif

Understanding how Chemoradiotherapy Promotes Glioblastoma Tumor Recurrence

The current standard of care for GBM patients involves surgery followed by radiation and/or chemotherapy. While this may be effective at eliminating most of the tumor cells in the short term, the majority of GBM patients will relapse within seven to nine months. These recurrent tumors are highly aggressive and resistant to virtually all available treatments, and the patient will eventually succumb to the disease. There is an urgent need to understand why tumor recurrence occurs so often in GBM patients and improve the current standard of care.

Recent research has found that chemoradiotherapy, in addition to slowing the growth of tumor cells, may also unexpectedly promote tumor recurrence. Chemoradiotherapy causes damage to the DNA of cancer cells, leading to the activation of proteins called tumor suppressors. These tumor suppressors, as the name suggests, will suppress the growth of tumor cells. However, our recent work has uncovered an unconventional role of the so-called “tumor suppressor” protein TP73 in promoting GBM cell growth. In this project, we will investigate how chemoradiotherapy alters TP73 expression and activity and whether TP73 plays a role in promoting tumor recurrence.

This project will allow us to better understand how GBM cells respond to chemoradiotherapy. The knowledge generated from this project will allow us to design better therapeutic strategies to help improve outcomes for GBM patients.

Dr. Peter Thompson

Designing a Targeted Drug Delivery System for Beta Cells in Type 1 Diabetes

Type 1 diabetes (T1D) is a life-long disease where the body loses the ability to produce the essential hormone insulin because the immune system mistakenly destroys the beta cells in the pancreas. T1D is often diagnosed in children, affecting one in 300 Canadians and approximately 13,600 in Manitoba alone.

While insulin is required to manage the disease, it is not a cure. Children and adults living with T1D are at risk for a variety of health complications and there is currently no way to prevent this disease.

Remarkably, some of the beta cells are actually culprits in triggering T1D. These harmful beta cells acquire a cellular sickness that promotes disease development. Removal of these sick beta cells with drug therapy spares the healthy ones and prevents the disease, akin to getting rid of rotten apples to save the good ones. However, these drugs are currently limited in their ability to specifically target the sick beta cells, hampering efforts to bring this promising new approach to the clinic.

All cells produce and export small cargo units that are like mail packages or shipping containers to communicate with other cells. Interestingly, this cargo delivery system can be programmed with specific addresses in order to deliver cargo to specific cell types in the body.

This project seeks to harness the cell’s cargo delivery system as a better approach to target drugs to sick beta cells for T1D preventive therapy. These studies will take us a step closer towards safe and effective ways to prevent T1D.

Dr. Jarret Woodmass

Jarret Woodmass — Randomized Clinical Trial Comparing Reverse Total Shoulder Arthroplasty with and Without Subscapularis Repair

The shoulder is a “ball and socket” joint that can become severely arthritic. A total shoulder arthroplasty (TSA) replaces arthritic bones, but some patients also have torn shoulder muscles so a standard TSA does not work. When this happens, surgeons must switch or “reverse” the natural position of the ball and socket to compensate for the torn muscles. This technique is called a reverse TSA (RTSA).

An additional procedure is sometimes done with a RTSA called a subscapularis repair.  Some surgeons feel this reduces the risk of shoulder dislocation while others feel it may restrict movement too much. There has never been a study to compare these approaches. The main goal of this study is to compare a RTSA with and without subscapularis repair.

Eighty-four patients with shoulder arthritis and severe rotator cuff injury will be randomly assigned to have a subscapularis repair or no repair. The main outcome is a patient-reported questionnaire that asks patients to rate their pain and ability to perform daily activities. Range of movement and rates of shoulder dislocation will also be compared.

The surgeons involved in this study perform all RTSA procedures done in Manitoba. Therefore, we have an incredible opportunity to potentially involve all patients that require this surgery from our population to evaluate their outcomes and to improve care for patients like them across the world. This study is critical in guiding surgeons to make the best choice for their patients and maximizing the outcome of this major shoulder procedure.

If you have any questions about our past operating grant recipients report or if you would like to receive a hard copy of
annual award, please contact us at 204.788.6801 or email us info@mmsf.ca
arrow_upward