Medicine and Health Sciences Commons^™

Data-Driven Decision Support Tool Co-Development With A Primary Health Care Practice Based Learning Network, Jacqueline K. Kueper, Jennifer Rayner, Sara Bhatti, Kelly Angevaare, Sandra Fitzpatrick, Paulino Lucamba, Eric Sutherland, Daniel J. Lizotte

Epidemiology and Biostatistics Publications

Background: The Alliance for Healthier Communities is a learning health system that supports Community Health Centres (CHCs) across Ontario, Canada to provide team-based primary health care to people who otherwise experience barriers to care. This case study describes the ongoing process and lessons learned from the first Alliance for Healthier Communities’ Practice Based Learning Network (PBLN) data-driven decision support tool co-development project.

Methods: We employ an iterative approach to problem identification and methods development for the decision support tool, moving between discussion sessions and case studies with CHC electronic health record (EHR) data. We summarize our work to date in …

Developing A Model To Assess The Contribution Of Cytokeratin 19-Expressing Cells During Multipotent Stromal Cell-Induced Islet Regeneration, Brianna Ananthan

Electronic Thesis and Dissertation Repository

Previously, pharmacological activation of Wnt-signaling in human bone marrow-derived multipotent stromal cells (hMSC) generated conditioned media (CM) that promoted β-cell regeneration in streptozotocin-treated mice. Ductal-derived endocrine progenitors, which have been shown to generate β-cells following pancreatic injury, represent a candidate for the ‘signal-receiving cell’. Ductal (CK19+) cells from mice pancreata obtained by purification of live Dolichos Biflorus Agglutinin lectin+ cells and cultured in minimal media supplemented with Untreated, Wnt-activated, or Wnt-inhibited CM demonstrated a significantly increased proportion of EdU+/CK19+ cells following 48-hours of supplementation but no endocrine phenotype acquisition. Lineage-tracing CK19-CreERT;Ai9(RCL-tdT) mice treated with tamoxifen (single dose) demonstrated specific labeling …

Printed Educational Materials Directed At Ontario Primary Care Physicians Fail To Improve Adherence To Guideline Recommendations For The Management Of Diabetes Complications: A Pragmatic, Factorial, Cluster Randomized Trial, Alison Howie

Electronic Thesis and Dissertation Repository

Printed educational materials (PEMs) have long been used as a tool for knowledge translation despite the conflicting evidence surrounding their effectiveness. A pragmatic, 2x2 factorial, cluster-randomized controlled trial was designed to ascertain the effectiveness of two distinct formats of a PEM (insert and outsert) at improving adherence to guideline recommendations for the management of diabetes complications among Ontario family and general practitioners. Administrative databases were used to compare patient’s treatment regimens at baseline and one year following PEM mailout to determine whether prescription rates intensified in response to the PEMs. A total of 4,118 practices (4,957 physicians) and 185,454 patients …

Regulation Of Glucagon Secretion And Trafficking By Proteins In The Glucagon Interactome, Farzad Asadi Jomnani

Electronic Thesis and Dissertation Repository

Patients with diabetes exhibit hyperglucagonemia, or excess glucagon secretion. The glucagonocentric hypothesis of diabetes states that hyperglucagonemia, rather than hypoinsulinemia, may be the underlying mechanism of hyperglycemia of diabetes. Thus, uncovering mechanisms that regulate glucagon secretion from pancreatic α-cells is crucial for developing treatments for hyperglycemia. One clue to the regulation of glucagon secretion may lie in the proteins that interact with glucagon in α-cell’s secretory pathway, primarily within the secretory granule. The purpose of my work was to identify proteins that interact with glucagon within the secretory granule and characterize a candidate protein within this network that regulates the …

Therapeutic Interventions For Managing Diabetic Shoulder, Sanaa A. Alsubheen

Electronic Thesis and Dissertation Repository

Shoulder pain is a common complaint of diabetic patients that causes motion limitations and functional disability. Adhesive capsulitis (AC) is the most common disabling shoulder disorder. There is no optimal non-surgical treatment for managing AC in diabetic patients. Furthermore, the impact of diabetes on shoulder recovery and factors predicting shoulder function following shoulder arthroplasty is not well investigated.

Purpose and Methods

The main purpose of this thesis was to inform clinical practice about the best intervention for managing AC in diabetic patients, and to assess the impact of diabetes on functional outcomes after shoulder arthroplasty, with the following objectives: 1) …

Identification Of Human Postnatal Progenitor Cells With Multifaceted Regenerative Functions, Tyler T. Cooper

Electronic Thesis and Dissertation Repository

Regenerative medicine is a multidisciplinary effort to regenerate or replace a deficiency of functional cells/tissues, such as deteriorated vasculature in cardiovascular pathologies or depleted -cell mass in diabetes. The transplantation of pro-regenerative progenitor cell populations has demonstrated therapeutic benefits in pre-clinical models, although translation to clinical efficacy is limited by the paradoxical balance between cell expansion ex vivo and loss of regenerative functions in vivo. Herein, this thesis encompasses two distinct approaches to circumvent translational deficiencies; 1) prevention of hematopoietic progenitor cell differentiation during ex vivo expansion and 2) utilizing the secretome of pancreas-derived multipotent stromal cell as a …

The Indigenous Determinants Of Health As Predictors For Diabetes And Unmet Health Needs Among Urban Indigenous People: A Respondent-Driven Sampling Study In Toronto, Ontario, Stephanie Rachael Mcconkey

Electronic Thesis and Dissertation Repository

National statistics commonly present Indigenous peoples as a falsely homogenous group of people experiencing disproportionate ill health when compared to non-Indigenous peoples. There are significant gaps in statistical information regarding the health services access barriers experienced by Indigenous people that disrupts the quality of care they receive or prevents them from accessing care altogether. Our Health Counts Toronto is a community-based study that employed respondent-driven sampling (RDS) methodologies to sample 917 urban Indigenous adults. Prevalence estimates and prevalence ratios were calculated using RDS-II weights and adjusting for clustering by shared recruiter in SAS 9.4 and SAS-callable SUDAAN 11.0 software. This …

Increased Mitochondrial Calpain-1 Is An Important Mechanism Contributing To Mitochondrial Ros Generation In Cardiac Diseases, Rui Ni

Electronic Thesis and Dissertation Repository

Both calpain activation and excessive mitochondrial reactive oxygen species (mtROS) have been implicated in the pathogenesis of cardiac diseases. We investigated whether and how calpain regulates mtROS generation in mediating cardiac diseases.

In mouse models of streptozotocin-induced type-1 diabetes and lipopolysaccharides- induced sepsis, we show that the protein levels of calpain-1 and calpain activities in mitochondria were significantly elevated in diabetic and septic hearts. The elevation of mitochondrial calpain-1 correlated with an increase in mtROS generation and oxidative damage. Importantly, cardiomyocyte-specific deletion of capns1 disrupted calpain-1 and calpain-2 in the heart and prevented mtROS generation in both septic and diabetic …

Exploring Quality Improvement For Diabetes Care: A Multiple Case Study Of Primary Care Teams In First Nations Communities In Canada, Meghan Fournie

Electronic Thesis and Dissertation Repository

Clinical quality improvement (QI) teams from First Nations communities across Canada participated in an 18-month QI collaborative program called the TransFORmation of IndiGEnous Primary HEAlthcare Delivery (FORGE AHEAD) clinical QI initiative. Community-based participatory research and multiple case study methodologies were utilized to explore the experience of two clinical QI teams from diverse primary care settings in First Nations communities as they engaged in developing and implementing changes in practice to improve the quality of diabetes care. This study provides insight into how clinical QI teams drew upon multiple sources of knowledge and information to inform their QI activities, the importance …

It's About Time! Gdm: A Transformative Postpartum Process. A Constructivist Grounded Theory Study, Natalie Giannotti

Electronic Thesis and Dissertation Repository

Abstract

Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance with onset or first diagnosis during pregnancy, and affects 3.7%-18% of Canadian women (Canadian Diabetes Association, 2013). Social support can help women with a history of GDM be successful in achieving optimal health postpartum. The purpose of this constructivist grounded theory (GT) study (Charmaz, 2011) was twofold: (1) To explore the social support processes of women with a history of GDM as they navigate through the healthcare system postpartum, to restore and maintain their health, and (2) To critically examine facilitating factors and barriers to engaging in health behaviours within …

Proteomic Characterization Of Human Multipotent Stromal Cells Secreted Proteins With Therapeutic Potential For Β-Cell Regeneration, Miljan Kuljanin

Electronic Thesis and Dissertation Repository

Novel strategies to stimulate the expansion of β-cell mass in situ are warranted for diabetes therapy. Cell-replacement therapies for the treatment of diabetes have become a focal point in recent years. Endogenous regeneration of β-cell mass has been demonstrated using human multipotent stromal cells (hMSC). However, the secretory factors responsible for initiating endogenous regeneration remain unknown. Successful large-scale proteomic applications to address these questions have been limited in part by difficulties in correctly selecting the appropriate methodologies. Thus, the goal of this thesis was a combination of assessing different proteomic workflows to facilitate investigation into hMSC biology, applying these methods …

A Clinico-Pathological Study Of The Structural And Functional Changes In The Retina And Optic Nerve Following Diabetic Retinopathy Treatments, Richard Filek

Electronic Thesis and Dissertation Repository

Diabetic retinopathy (DR) is the result of microvascular changes in the retina due to hyperglycemia which alter the blood-retinal barrier (BRB). The increased permeability of BRB results in the accumulation of extracellular fluid, the development of diabetic macular edema (DME) and capillary occlusion. Capillary occlusion results in retinal ischemia which increases vascular endothelial growth factor (VEGF) levels, increases vascular permeability and results in neovascularization in proliferative diabetic retinopathy (PDR) patients. The treatments clinically used for DR are panretinal photocoagulation (PRP) for PDR and injectable vascular endothelial growth factor inhibitors (anti-VEGFs) for DME.

The safety of PRP and anti-VEGF therapy on …

Retinoic Acid Pathway Inhibition To Expand Human Hematopoietic Progenitor Cells With Islet Regenerative Capacity, Ruth Elgamal

Electronic Thesis and Dissertation Repository

Cellular therapy to induce islet regeneration is emerging as a novel treatment strategy for diabetes. Umbilical cord blood (UCB)-derived hematopoietic stem/progenitor cells (HSPC) isolated by high aldehyde dehydrogenase activity (ALDH^hi) reduce hyperglycemia after transplantation into streptozotocin (STZ)-treated NOD/SCID mice. However, UCB-derived ALDH^hi cells are rare and expansion without the loss of regenerative function is required. We hypothesized that BMS 493, an inverse retinoic acid receptor agonist, will prevent HSPC differentiation of HSPC during expansion, generating more ALDH^hi cells for therapy. ALDH^hi cells expanded for 6 days with BMS 493 showed a 2.70-fold-increase in ALDH^{hi …}

The Long Non-Coding Rna Malat1 Regulates Inflammatory Cytokine Production In Chronic Diabetic Complications, Andrew D. Gordon

Electronic Thesis and Dissertation Repository

We examined the role of MALAT1, a highly conserved nuclear lncRNA, in chronic diabetic complications affecting the heart and kidneys, specifically with respect to inflammatory cytokine production. Endothelial cells, exposed to various glucose levels, and MALAT1 knockout mice and controls, with or without streptozotocin-induced diabetes were examined. Endothelial cells cultured with high glucose, and renal and cardiac tissue from diabetic mice showed increased inflammatory cytokine (eg. IL-6, IL1β, TNFα) production along with transient MALAT1 upregulation. This was confirmed by both transcript and protein analyses, and such changes were prevented in the MALAT1 knockout diabetic animals. In the malat1 knockout animals, …

An Investigation Of Health Literacy, Acculturation, Diabetes Knowledge, And Social Supports Among Latinos With Diabetes In Southern Ontario, Ivonne Aguilar

Electronic Thesis and Dissertation Repository

The prevalence of diabetes is high among Latino people. This study investigated the relationships between health literacy, acculturation, social support, and diabetes-related knowledge among Latino adults with Type 2 diabetes and informal caregivers with a family history of Type 2 diabetes. A non-experimental, cross-sectional design was used to examine these relationships among 73 adult Latino participants living in Southern Ontario. Based on Nutbeam’s conceptualization of health literacy, associations existed between health literacy, acculturation and knowledge of diabetes among Latino participants, yet the concept of social support showed no direct relationship to health literacy. This research has explored the factors that …

Antihyperglycemic Medications And Hypoglycemia In Older Adults With Diabetes, Kristin K. Clemens

Electronic Thesis and Dissertation Repository

Background: In the last decade, several new antihyperglycemic medications have been approved to treat people with diabetes. However, the hypoglycemia risk of these medications in older adults in routine clinical practice remains unclear. Further, there is limited understanding as to how these medications are being prescribed to older adults in our region.

Methods: We carried out retrospective, population-based studies of adults age 66 and older in Ontario, Canada using linked healthcare databases. We first investigated the real-world hypoglycemia risk of 2 antihyperglycemic medications – glyburide and modified-release gliclazide. In an ecological study, we then examined trends in antihyperglycemic medication prescriptions, …

Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin

Electronic Thesis and Dissertation Repository

ii Abstract Abstract Defects in the proliferation, differentiation, and activity of bone marrow (BM)-derived vasculogenic/vascular stem cells (VSCs) have been observed in diabetes and contribute to the development of vascular complications. Diabetes leads to enhanced bone marrow adipogenesis, altering the composition of the BM stem cell (SC) niche and potentially disrupting the normal functioning of resident VSCs. Here, I establish that adipocytes have a negative influence on SC survival in culture. I also show that adipocytes and osteoblasts are responsible for the creation of distinct extracellular microenvironments, with unique expression patterns of several pro- and anti-angiogenic factors with known effects …

Pancreatic Beta Cell Plasticity And Involvement Of Insulin-Expressing Progenitor Cells, Christine A. Beamish

Electronic Thesis and Dissertation Repository

Islet transplants have been successfully used as treatment for diabetes, but are limited by shortages of cadaveric insulin-producing β-cells. An alternate source may be the dedifferentiation, expansion, and subsequent redifferentiation of pancreatic islets or β-cells using in vitro techniques prior to transplant. Based on protocols which described the dedifferentiation of human islets to ductal-like cells, we hypothesized that neonatal mouse islets could be similarly dedifferentiated in vitro. Dedifferentiation techniques produced significant duct-like cells, but redifferentiation to insulin-expressing cells was limited. RIPCre;Z/AP+/+ mice were consequently utilized to lineage trace β-cell fate during culture by a human placental alkaline phosphatase (HPAP) reporter. …

Nerve Blood Flow Control In Health & Disease:The Effects Of Type 1 Diabetes And Exercise Training, Terry D. Olver

Electronic Thesis and Dissertation Repository

Peripheral nerve blood flow (NBF) is critical to nerve health. Impaired NBF control may contribute to the progression of diabetes peripheral neuropathy. The purposes of this dissertation were: i) to investigate the acute and chronic effects of hyperglycemia on basal sciatic NBF (measured via Doppler ultrasound), ii) to examine the potential vasodilatory effects of insulin (euglycemic hyperinsulinemic clamp; 10 mµ•kg^-1•min^-1) on NBF control in healthy rats and rats with insulin-treated type 1 diabetes (DS) and iii) to determine if exercise training (~75% VO₂max, 60 min/day, 5 days/wk for 10 wk) improves vasa nervorum reactivity …

Vascular Stem Cells In Diabetic Complications, Emily C. Keats

Electronic Thesis and Dissertation Repository

Diabetes leads to a variety of secondary complications. At the heart of these complications lies endothelial cells (ECs) – cells that take up unregulated plasma glucose, experience various biochemical alterations, and provide the basis for whole organ vascular dysfunctions. With the purpose of generating new vascular networks for the treatment of these chronic complications, my initial work focused on vascular stem cells (VSCs). VSCs have the ability to differentiate into both endothelial (EPC) and mesenchymal (MPC) progenitor cells, both of which are necessary for the creation of stable and functional blood vessels. To establish whether these progenitor populations retain their …

Quality Indicators Of Diabetes Care: An Example Of Remote-Area Aboriginal Primary Health Care Over 10 Years, Julia V. Marley, Carmel Nelson, Vicki O'Donnell, David Atkinson

Aboriginal Policy Research Consortium International (APRCi)

To describe service characteristics of Derby Aboriginal Health Service (DAHS) and document diabetes management activities and intermediate clinical outcomes for Aboriginal patients with type 2 diabetes.

Elucidating The Function Of Transplanted Islets Of Langerhans And Predicting Their Ability To Reverse Diabetes, Andrew R. Pepper

Electronic Thesis and Dissertation Repository

Type 1 diabetics require daily injections of exogenous insulin to control hyperglycemia. Unfortunately, patients are still plagued by vascular and hypoglycemic complications. Beta cell replacement therapy by either whole organ pancreas or islet transplantation has been shown to restore carbohydrate control to these patients. A major barrier to successful islet transplantation is the lack of a reliable pre-transplant assay of post-transplant function thus providing an objective measure of whether a particular islet isolation should be transplanted. Such an assay would also prove to be a valuable tool in the experimental evaluation of innovative islet isolation strategies and technologies. The initial …

Uwomj Volume 78, Issue 1, Western University

University of Western Ontario Medical Journal

Schulich School of Medicine & Dentistry

Uwomj Volume 78, Supplement S1, Summer 2008, Western University

University of Western Ontario Medical Journal

Schulich School of Medicine & Dentisty

Long-Term Trends In Indigenous Deaths From Chronic Diseases In The Northern Territory: A Foot On The Brake, A Foot On The Accelerator, David P. Thomas, John R. Condon, Ian P. Anderson, Shu Q. Li, Stephen Halpin, Joan Cunningham, Steven L. Guthridge

Aboriginal Policy Research Consortium International (APRCi)

Objective: To examine trends in Northern Territory Indigenous mortality from chronic diseases other than cancer. Design: A comparison of trends in rates of mortality from six chronic diseases (ischaemic heart disease [IHD], chronic obstructive pulmonary disease [COPD], cerebrovascular disease [CVD], diabetes mellitus [DM], renal failure [RF] and rheumatic heart disease [RHD]) in the NT Indigenous population with those of the total Australian population.

Participants: NT Indigenous and total Australian populations, 1977–2001. Main outcome measures: Estimated average annual change in chronic disease mortality rates and in mortality rate ratios. Results: DeathratesfromIHDandDMamongNTIndigenouspeoplesincreased between 1977 and 2001, but this increase slowed after 1990. …

Aboriginal Health Workers And Diabetes Care In Remote Community Health Centres: A Mixed Method Analysis, Damin Si, Ross S. Bailie, Samantha J. Togni, Peter H N D'Abbs, Gary W. Robinson

Aboriginal Policy Research Consortium International (APRCi)

Objective: To assess the effect of employing Aboriginal health workers (AHWs) on delivery of diabetes care in remote community health centres, and to identify barriers related to AHWs’ involvement in diabetes and other chronic illness care.

Design, setting and participants: Three-year follow-up study of 137 Aboriginal people with type 2 diabetes in seven remote community health centres in the Northern Territory.

Main outcome measures: Delivery of guideline-scheduled diabetes services; intermediate outcomes (glycated haemoglobin [HbA1c] and blood pressure levels); number and sex of AHWs at health centres over time; barriers to AHWs’ involvement in chronic illness care.

Results: There was a …