Foundation Funded Projects for 2017

October 1 to December 31, 2017

July 1 to September 30, 2017

January 1 to March 31, 2017

April 1 to June 30, 2017


January 1 to March 31, 2017



Dr. T. Freeman
Dr. M. Stewart

Western University

Symptoms and relevant outcomes: SMART

People visit family physicians with sensations (symptoms) which may or may not be due to a disease. Two-thirds of patients visit a family physician for a symptom, of which 35% are not given a disease label at the end of that visit. It is the task of the family physician to figure out which symptoms are associated with a disease or require investigation, and which can be safely cared for without a disease label. The proposed study will provide information to family physicians on 10 common symptoms answering the following questions. For each symptom, what percent are given a new diagnosis at the end of the visit? What percent are connected to an old diagnosis? What percent remain labelled as a symptom and how many future visits are needed before a diagnosis is made? Finally, the study will link patient characteristics (such as age, sex and prior conditions) with whether or not the symptom is diagnosed. This information will help with patients and family physicians to better understand and care for common symptoms.



Dr. K. Kersti
Muskoka Algonquin Healthcare

Postgraduate Diploma in Clinical Dermatology



Dr. F. Mahmud
Dr. M. Marcon

Hospital for Sick Children

Celiac disease and Diabetes Longitudinal Follow-up and Evaluation Study (CD-LiFE): a longitudinal study evaluating dietary factors, metabolic control and complications and, self-perceived health and wellness in type 1 diabetes patients with celiac disease

Celiac Disease (CD) occurs in people with Type 1 Diabetes (T1D) at rates 5-10 times that of the general population with most patients showing no obvious clinical signs or symptoms. Recent research has shown higher rates of diabetes related complications, including eye and kidney disease in patients with both CD and diabetes. Treatment of CD is with a gluten-free diet (GFD), which can make managing diabetes more difficult. It is also not known if the significant dietary and lifestyle change of a GFD is optimal for people to take care of both CD and diabetes while avoiding negative health outcomes.

This study will evaluate children and adults who with both CD and diabetes who have screened as part of a large clinical trial in Ontario. The investigators will examine the impact of dietary choice and adherence with a gluten-free diet on overall diabetes care, quality of life, and self-perceived health. In addition, the investigators will also follow patients for up to 10 years to track longer term health outcomes. This research will help guide care practice for clinics and patients managing two significant chronic health conditions with the overall goal of evaluating health outcomes in this unique group of patients.



Dr. O.N. Pathmanaban
Dr. M.D. Cusimano

St. Michael's Hospital

Tranexamic acid in the treatment of residual chronic subdural hematoma: a single-centre, observer-blinded, randomized, controlled trial

Chronic subdural hematoma (CSDH) is a common disease after minor head injury in older people. Blood collects on the surface of the brain, causing headaches, confusion, weakness or even coma. The best treatment is surgery, where a small hole is made in the skull and the blood is drained. Patients usually do well, but some of the blood remains after surgery and there is up to 30% chance of more bleeding and the CSDH getting bigger again. A medicine capable of reducing the chance of further bleeding is therefore desirable.

In this study, the investigators will test a drug called Tranexamic Acid (TXA). The body stops unwanted bleeding naturally by forming blood clots; TXA stops these blood clots dissolving (antifibrinolytic), helping to keep bleeding spots plugged. TXA has been shown to decrease hematoma volume in a small group of CSDH patients. The investigators hypothesize that TXA can help reduce the remaining volume of CSDH after surgery and lower the chance of it getting bigger again. Half of the patients in this study will be randomly assigned to take TXA tablets, while the other half will take placebo. Remaining CSDH after burr-hole surgery will be measured over time to quantify treatment success.



Dr. T. L. Roy
Dr. A. D. Dueck

Sunnybrook Health Sciences Centre

Magnetic resonance imaging (MRI) in the assessment of peripheral arterial disease

Peripheral arterial disease (PAD) is a morbid, mortal and prevalent condition that affects over 800,000 Canadians. It is one of the most common cardiovascular diseases. Decreased blood flow to the leg causes exertional pain and is associated with poor quality of life and disability. When PAD is severe it is called “critical limb ischemia”. In this subset of patients, major amputation is required within 1 year in up to 40% of patients.

Current treatment options for PAD involve re-establishing blood flow to the leg through either bypass surgery or percutaneous vascular intervention (PVI). PVI is an attractive, minimally invasive approach with improved morbidity and shorter length of hospital stay compared to surgery. However, not all lesions are amenable to PVI and it has a high failure rate of 20% and high re-intervention rate of 30%. PVI is guided with x-ray fluoroscopy, which offers very limited visualization of the diseased arteries in the leg, making it difficult to predict if PVI would be successful or even possible to treat specific patients. Prompt, definitive revascularization is necessary to avoid major amputation, and appropriate patient selection is critical.

MRI is capable of producing high quality images of the blood flow in the legs. In our study, we will develop and validate MRI methods of visualizing diseased arteries in the leg to facilitate PVI planning. MRI has the potential to significantly advance the treatment of PAD by enabling physicians to make more effective decisions with respect to patient selection to reduce PVI failure rates. MRI also holds significant promise to characterize diseased arteries to facilitate tailored wire and device selection to improve the success rates and durability of PVI. Informed patient, wire and device selection is key to improving amputation rates, disability outcomes and quality of life in this growing patient population.



Dr. J. Yoon
Dr. B. Clarke

University Health Network

DICER1 in uterine rhabdomyosarcoma, adenosarcoma and carcinosarcoma - a potential diagnostic tool for molecular distinction

Study of rare tumours has allowed researchers to identify genes important for cancer formation/progression, as well as identifying potential therapeutic targets. DICER1 is such a gene with numerous roles in the gynaecological tract, including development and fertility, as well as being implicated in uterine cancer. Based on previous works, including works by the collaborator, the investigators propose that a specific gynaecological tract tumour, known as embryonal rhabdomyosarcoma, is associated with mutations in the DICER1 gene. To prove this idea, the investigators are employing the state-of-art sequencing technology to examine for mutations in the DICER1 gene. By comparing features seen under the microscope, DNA sequence data and clinical data, the investigators can test their hypothesis and determine the significance of mutated DICER1. The obtained results will be important for both the patient and their family members, as inherited mutations in DICER1 increase risks for a number of different diseases.

April 1 to June 30, 2017



Dr. F. Amin*
Dr. C. Demers

McMaster University

Evaluation of the Impact of Primary Care Heart Failure Billing codes on Clinical Outcomes

Heart failure (HF) is the most frequent cause of hospital admission for adults in Ontario. In 2008 the Ontario Ministry of Health and Longterm Care (MOHLTC) introduced an annual billing code, Q050A, for family doctors encouraging best practices for HF care. Data from 2008-2014 shows that MOHLTC has spent over $11.5 million to compensate family doctors using this code. However, the impact of this financial incentive on patients' health remains unclear. The present study aims to determine whether this incentive billing code, Q050A, has reduced emergency room visits, hospitalizations and death amongst patients who have HF. We will use anonymous health data stored at the Institute of Clinical Evaluative Sciences to perform our analysis. Overall, the study aims to evaluate the impact of the Q050A billing code to guide future provincial initiatives aimed at improving the health of patients with HF.



Dr. C.D. Bernard
Dr. M.K. Kulasegaram

University of Toronto

From classroom to clinic: assessing a novel integrated curriculum to teach ethical decision making for future physicians

Ethical reasoning and judgement is one of the foundations upon which trusting and caring relationships are formed with patients. However, it is an aspect of practice for which doctors in training, feel underprepared and unconfident – a view shared by many practicing Family Physicians. And despite ethics' importance to practice, the best approaches to teaching it in post-graduate medical training are unknown and debatable.

The goal of this study is to evaluate the efficacy and utility of a novel ethics curriculum for postgraduate Family Medicine trainees at the University of Toronto. The curriculum is based on the emerging field of learning sciences. Using concepts from psychology and education, this body of knowledge explains how to teach and train in ways congruent with how the mind and brain work. The curriculum uses this knowledge to better prepare doctors to apply ethical principles when they see patients in the clinical setting.

The theory-driven evaluation will compare the new curriculum to traditional teaching methods. We will examine the impact of the ethics curriculum across multiple community and hospital teaching sites at the University of Toronto Family Medicine program. The anticipated outcome is to show the efficacy and feasibility of this new approach as well as to highlight the best principles for training ethically competent physicians.



Dr. M. Bhandari
Dr. G. Slobogean

McMaster University

A Pragmatic Randomized trial Evaluating Pre-operative Antiseptic skin solutions in fRactured Extremities (PREPARE)

Open fractures represent the most severe musculoskeletal injuries. Patients with open fractures frequently experience surgical site infections (SSIs) which can result in devastating consequences such as prolonged morbidity, loss of limb function, and potential limb loss. The investigators' previous research has found that simple measures may lead to dramatic improvements in open fracture patients. Additionally, data from their recent study of over 2,400 open fracture patients has shown that the type of antiseptic skin solution applied to the fractured limb in the operating room may affect outcomes. Therefore, the investigators propose a cluster randomized crossover trial that will enroll open fracture patients to test the central hypothesis that iodophor-based pre-operative solutions are more effective than chlorhexidine solutions to reduce open fracture SSIs.

The primary objective of the definitive trial is to determine the most effective pre-operative antiseptic skin solution to reduce SSIs during open fracture management. Participants will be followed up to 90 days. The primary rationale for the proposed trial is the need to reduce avoidable SSIs and their negative impact on open fracture patients. Prior to initiating this large definitive trial, a pilot trial is necessary to demonstrate the feasibility of this novel study design.



Dr. M. Coffey
Hospital for Sick Children

High reliability organizing in healthcare: Caring Safely at the Hospital for Sick Children

Patient safety has become an international hospital priority given the magnitude of preventable harm caused by medical care. Although gains have been made in patient safety over the past 15 years, progress has been slower than expected. Patient safety experts suggest that a high reliability organizing approach that fosters safety culture can advance the patient safety agenda. This approach is drawn from high-risk industries that have successfully avoided catastrophes despite their complexity. However, evidence around this organizational approach in healthcare is lacking. Research on its implementation process is particularly essential to understanding the complex processes, practices and consequences involved. This evidence is critical given the significant implications of a high reliability organizing intervention for patient care, medical and other health professionals' practices, and resources. In this study, the innovative, large-scale, ‘Caring Safely' program at SickKids will be studied to examine how its aim to implement high reliability organizing is influencing patient safety culture and preventable harms. Using interviews, observations and documents, this study will explore how hospital leaders, healthcare providers and family advisors, are interpreting and practicing ‘Caring Safely'. The findings will provide in-depth insights underscoring the social processes and contextual factors that characterize organizational change for improving patient safety.



Dr. S. Kilty
Ottawa Hospital Research Institute

Health Economic Evaluation of Endoscopic Polypectomy Performed in Clinic (EPIC) for Patients with Chronic Rhinosinusitis

Chronic sinusitis is one of the most common chronic diseases in North America, with over 5% of the Canadian population affected by the disease. Until now, treatment with surgery has been performed only in the operating room. Recently, a smaller surgical procedure that is done in the clinic for patients with chronic sinusitis with polyps has been found to result in symptom control that appears similar to that which occurs with sinus surgery. Performing the smaller less invasive clinical procedure has advantages including a shorter patient wait time for the procedure and a shorter recovery time for the patient. However, the value for money of this small procedure remains unknown. We will therefore conduct a study to compare costs and outcomes of the small clinical procedure to a usual care to determine whether the benefits of the small surgical procedure justify its costs. If the in clinic treatment is found to be less expensive while providing at least an equal improvement in patient's quality of life, this will aid tremendously to support clinician adoption of this new clinic procedure.



Dr. A. Laliberte*
Dr. T. Waddell

University Health Network

According to North American literature, the standard of care for empyema consists of antibiotic and tube drainage in the majority of patients. Surgical intervention is required when there is prolonged or uncontrolled sepsis, or for trapped lung. The MIST-2 trial has revolutionized the treatment of empyema, using 10mg TPA combined with 5mg of Dnase twice a day for six doses. This showed that by using TPA and Dnase, fluid drainage can be improved, and both surgical intervention and length of stay can be decreased. This is now the standard of care for most thoracic surgeons. At UHN, a combination of intrapleural 4mg TPA with 5mg Dnase is used to treat empyema. The dose of 4mg of TPA has been used at UHN, however, there is no data supporting that dose. At Sunnybrook Health Sciences Center, the dose of intrapleural TPA used is 10mg daily for three days. Therefore, the Investigators are using this as the control group. 384 charts will be reviewed for retrospective data (192 from each group). Primary outcome is to determine whether intrapleural TPA 4mg is as efficient as intrapleural TPA 10mg in the treatment of empyema when it is used in combination with Dnase. Secondary outcome is to determine if the rate of complications, the need for surgery, and the length of stay is equivalent with TPA 4mg compared to TPA 10mg.

A p-value of less than 0.05 will be considered significant.



Dr. N. Neufeld*
Dr. A. Voineskos

Centre for Addiction and Mental Health

After two adequate antipsychotic medication trials, patients with schizophrenia can be declared as having treatment-resistant schizophrenia (TRS) and become eligible for a trial of clozapine (CLZ). Identification of patients with TRS and treatment as early as possible in the disease course is a high priority. Yet early identification and management of TRS remains a major unmet need. Our work provides an opportunity to determine whether a baseline MRI scan can be used to identify functional connectivity patterns in TRS patients associated with response to CLZ. If successful, our pilot results will inform future longitudinal studies with the goal of translating these neuroimaging biomarkers into a predictor to further advocate for CLZ in patients who are likely to respond while mitigating the risks inherent in CLZ treatment for those who are unlikely to respond.



Dr. M. Palmert
Dr. J. Stinson

Hospital for Sick Children

Type 1 Diabetes Mellitus (T1DM) is a common chronic disease of childhood. T1DM has substantial impact on quality of life (QOL) [1], including burdensome dietary restrictions and the need to count carbohydrates in foods to safely dose insulin. Carbohydrate counting is challenging, inconvenient, and, if done wrong, can cause high or low blood glucose levels.

To address these challenges, iSpy, a novel smartphone application, was created to identify foods and determine their carbohydrate content using pictures or speech. This proposal is for youth-based usability testing of iSpy followed by a pilot study to see if using iSpy improves carbohydrate counting and freedom in food choices. The usability testing will involve scenario-based tasks while for the pilot study, 40 youth (20 using iSpy; 20 controls), aged 8-17 years, with T1DM will participate in a 3-month study. Pilot participants will have carbohydrate counting (accuracy and efficiency) and their freedom to eat a variety of foods assessed at baseline and after 3-months.

The investigators hypothesize that using iSpy will make carbohydrate counting easier (by improving accuracy and efficiency) and allow youth to eat a broader range of foods. If so, iSpy may help lessen the burden of living with T1DM.

1. Bradley, Clare, and Jane Speight. "Patient perceptions of diabetes and diabetes therapy: assessing quality of life."
Diabetes/Metabolism Research and Reviews 18.S3 (2002): S64-S69.



Dr. K. Quinn*
Dr. C. Bell

Sinai Health System

Approximately 3 million Canadians are hospitalized each year. Individuals who are admitted through the Emergency Department are potentially at an increased risk of death due to either the severity of their illness, or their reduced ability to withstand the effects of illness. This often occurs as individuals age or accumulate multiple medical conditions that may make them more prone to being hospitalized.

It may seem obvious that any unscheduled hospital admission would be associated with an increased risk of death, but no study has quantified that risk in individuals following their first hospital admission, or how the relationship between first hospitalization and risk of death might change as individuals age.

From a practical standpoint, by identifying an individual's risk of death after their first hospitalization, our study will provide important information that their doctors can use when talking to their patients and their family. For example, if admission to hospital is associated with a significant increase in an individual's risk of death, this important information should be conveyed to the patient and their family to help them understand their illness and potentially plan for the future.



Dr. M. Ruzicka
Dr. S. Hiremath

Ottawa Hospital Research Institute

Hypertension is the single most important risk factor for cardiovascular disease and death.

Over the last several decades many classes of blood pressure lowering drugs were discovered. This allows physicians to achieve in majority of patients with hypertension optimal blood pressure and prevent adverse cardiovascular outcomes.

Question indeed is: "What is that blood pressure target we should be aiming for?"
It became apparent that assessment of blood pressure is highly influenced by technique and device. in particular the length of resting time (if any), and whether it is measured with device requiring medical personnel presence in the room or not. For the same individual, the difference between blood pressure taken with and without rest could be 10 mmHg, and presence vs absence of medical personnel in the room during rest and/or BP assessment could be another 10 mmHg. Hence target blood pressure could vary materially based on BP technique and device used. As it is unlikely that all physicians could "overnight" change their practice and embrace blood pressure device allowing for standard resting time and unattended blood assessment, comparative pragmatic study of the blood pressure technique and devices endorsed by Hypertension Canada and used in Canada is desirable to avoid over-and under-treatment of Canadian patients with hypertension.

Results of this study will help and enable practicing family physicians and internists in Canada to target BP for their patients based on algorithm and method of assessment of BP they use in their offices. Something we, specialists behind the guidelines for the diagnosis and management of HTN, truly owe them.



Dr. J. Spence*
Dr. S. Connolly

McMaster University

Delirium is an acute state of confusion that is common after cardiac surgery, and it occurs in up to 50% of patients. Delirium is a serious concern, as it has been associated with long-term decreases in thinking ability, independent living, and even death. Benzodiazepines are a sedative medication that research has suggested may be associated in causing delirium. As such, they are not routinely used for sedation after cardiac surgery. However, they continue to be routinely used during cardiac surgery procedures, as they have minimal effects on blood pressure, which can be unstable in cardiac surgery patients. The investigators would like to compare the effect of a policy of intraoperative medication use that includes benzodiazepines to a policy that uses alternative medications on delirium after cardiac surgery. Both strategies are already used routinely; by standardizing them, the investigators hope to determine if one is better at preventing delirium after cardiac surgery.

July 1 to September 30, 2017



Dr. L. Bernard*
Dr. W. Faught

Ottawa Hospital Research Institute

Analysis of the socio-medical characteristics of Ontario cervical cancer patients

Despite the decrease in incidence of new cervical cancer diagnoses with the advent of screening, the disease remains an important cause of morbidity and mortality in Ontario. The investigators would like to better understand the medical and social characteristics of our cervical cancer patients to identify the most vulnerable population and better inform cervical screening policies and techniques.



Dr. M. Bonares*
Dr. A. Morris

Sinai Health System

A multi-centre investigation of the management and outcomes of community-onset Escherichia coli bacteremia

E. coli bacteremia is a common infection that is associated with high mortality. Currently there are no guidelines regarding the management of E. coli bacteremia. The objective of this study is to characterize the management of community-acquired E. coli bacteremia at 8 academic hospitals and to determine what factors, including an Infectious Diseases consultation, affect its outcomes.



Dr. M. Fehlings
University Health Network

Characterization of Blood Biomarkers in Patients with Degenerative Cervical Myelopathy to Direct Management and Prognosticate Clinical Outcome: A Prospective Cohort Study

Degenerative Cervical Myelopathy (DCM) is a devastating, progressive neurological disease resulting in the loss of hand function and impaired walking. The only proven treatment for DCM, surgical decompression of the spinal cord, can halt disease progression and promote recovery. Early surgery, prior to the onset of significant impairment, has the greatest potential for recovery. However, surgery is associated with the risk of complications and many patients with mild DCM remain stable over years. At present, clinical management for mild DCM patients frequently involves waiting for symptomatic progression before surgery is recommended.

Current management of mild DCM lacks a central consensus and is compounded by a lack of clinical tools to accurately predict if mild DCM will progress to a point where surgical intervention is required. Using clinically-relevant animal models and human pilot study samples, the Investigators have discovered blood biomarkers that can predict DCM status. The Investigators propose to test these newly discovered microRNA biomarkers in humans to diagnose, monitor and predict the progression of DCM. The Investigators predict that these microRNA biomarkers will provide clinicians with new tools to identify candidates for surgery before significant disease progression, reducing the suffering of patients and lowering the economic burden on the healthcare system.



Dr. B.N. Frey
McMaster University

A Translational Study of Blood-Brain Barrier Disruption in Bipolar Disorder: Implications for a new pathway for drug development

Bipolar disorder is a major mental illness that affects half a million Canadians. The exact causes of bipolar disorder are still unknown, but previous studies have shown that bipolar disorder is associated with high levels of inflammation and free radicals in the circulating blood. These free radicals typically do not enter in the brain because of a protective system called blood-brain barrier. However, if the blood-brain barrier is damaged, this could trigger inflammation inside the brain. The Investigators aim at investigating whether bipolar disorder is associated with damage in the blood-brain barrier. For that, they will recruit individuals with bipolar disorder during depressive states and will use brain magnetic resonance imaging (MRI) to study the blood-brain barrier. The Investigators will then repeat the MRI after treatment to investigate if successful treatment can fix the blood-brain barrier damage. They will also use a rat model to study if the mood stabilizer lithium protects the blood-brain barrier and to measure which blood-brain barrier proteins increase after lithium treatment. If successful, these studies (1) will link, for the first time, bipolar disorder with blood-brain barrier dysfunction and (2) will suggest a novel molecular pathway for the development of new treatments for this devastating illness.



Dr. S.S. Huang
London Health Sciences Centre

A Translational Study of Blood-Brain Barrier Disruption in Bipolar Disorder: Implications for a new pathway for drug development

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease where clots formed in the small blood vessels can lead to major organ injuries throughout the body, including the heart, and the brain. The effective treatment for TTP involves immediate plasma exchange, which is the removal of the fluid part of blood (plasma) in exchange for donor plasma. The immediate survival rate of the disease has improved from almost fatal to close to 80-90% due to plasma exchange. However, TTP is still associated with significant morbidity and mortality, even after plasma exchange treatment. The mortality rate has been shown to be almost 33% over 8 years. Therefore, there is a need to re-focus the management goal of these patients and prevent these injuries to the heart and the brain. To do so, there is a need to understand the impact of the disease in these patients. In this study the Investigators will follow 30 patients who have TTP, and have been successfully treated with plasma exchange therapy, over a 12-month period. The Investigators will apply advanced imaging tools and evaluate blood markers to understand the disease burden and its structural and functional impact on the heart and the brain.



Dr. B. Lanting
London Health Sciences Centre

Clinical Effectiveness, Cost-effectiveness, and Patient Satisfaction with Outpatient Total Hip and Total Knee Arthroplasty

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are among the most common orthopaedic procedures. Less invasive surgical techniques, improved management and comprehensive rehabilitation have enabled shorter inpatient stays. Eliminating the overnight hospital stay is a novel opportunity to improve economic efficiency; however, high quality evidenced-based comparisons to traditional inpatient models are lacking. Further, it is unknown whether the financial savings will be outweighed by additional postoperative costs, increased readmissions or decreased quality of care. The potential for an outpatient care model to have a significant impact on constrained healthcare budgets warrants a rigorous comparative trial. Therefore, our purpose is to conduct a multicenter randomized trial to evaluate outpatient care pathways for THA and TKA. The Investigators' objectives are to: 1) compare the rate of serious adverse events; 2) estimate the cost-effectiveness; and 3) evaluate satisfaction from the perspectives of patients, caregivers, and healthcare professionals, with the outpatient care pathway compared to the inpatient standard of care. Establishing patient safety and satisfaction while understanding the economic consequences, logistics and feasibility of outpatient THA and TKA will facilitate knowledge uptake, bringing this transformative care model into practice and promoting the sustainability of our publically-funded healthcare system. Patients allocated to the inpatient group will be discharged home according to standard protocol at each site (typically 2 to 4 days postoperative), and patients allocated to the outpatient group will be discharged on the same day as the procedure. The primary outcome is serious adverse events, defined as any event that requires readmission to hospital or additional surgical intervention. The secondary outcomes are cost, patient satisfaction, pain, Western Ontario McMaster Osteoarthritis Index (WOMAC), Harris Hip Score, Knee Society Score, SF-12, and EQ-5D.

The Investigators will determine the absolute risk of adverse events in each group, and calculate a relative risk (RR) with 95% confidence intervals around the estimate. They will calculate the mean and standard deviation for all secondary outcomes and calculate mean between-group differences with 95% confidence intervals. The Investigators will conduct a cost-effectiveness analysis from both a Canadian healthcare payer and societal perspective. We will calculate the incremental cost-effectiveness ratio (ICER), and estimate cost-effectiveness using the net benefit regression framework. To enhance the understanding of patient, caregiver and clinician experiences of the two care models, the Investigators will conduct a thorough assessment utilizing a descriptive qualitative approach.

The multidisciplinary team of investigators encompasses a breadth of expertise and experience. In addition to leading orthopaedic surgeons from top academic institutions, the team also involves investigators with expertise in health economics, epidemiology, knowledge translation, and qualitative research methodologies. The outputs of our study include evidence about the safety, effectiveness and economic consequences of an outpatient care pathway; an evaluation of the logistics and feasibility of program implementation to inform implementation at other institutions; and an evaluation of patient and caregiver satisfaction to ensure continued high quality of care.



Dr. L. Levy
Dr. T. Martinu

Toronto General Hospital

Risk stratification of sub-clinical acute rejection in lung transplantation

Lung transplantation is an option for appropriately selected patients with end-stage lung diseases. However, the average survival remains limited at 5 years only. The main obstacle to the long-term survival is the rejection of the transplanted lungs by the recipient's immune system, a process known as Chronic Lung Allograft Dysfunction (CLAD). Patients with CLAD have airways obstruction, similar to asthma, however, progressive and irreversible leading to severe shortness of breath and the need for oxygen.

One of the known risk factor to CLAD is events of “cute rejection”, which are very common among transplanted patients during the first year post transplant. At present, acute rejection is diagnosed using a tissue obtained by routine biopsies. However, this diagnostic method is invasive, very imprecise, and does not adequately identify patients who will progress to CLAD from patients who will not. Consequently, there is limited evidence to base the decision which patients need aggressive treatment for their acute rejection and which do not. The Investigators' objective is to better characterize the inflammatory cells on the biopsy and to identify proteins in the lungs that will enable them to predict which patients will remain stable and which patients will require additional treatment. The Investigators will investigate our question using samples previously obtained from our lung transplant patients and correlate them with later lung outcome.



Dr. U. Ndlovu*
Dr. S. Forbres

McMaster University

Surgical Outcomes of People Living with HIV/AIDS (SOPHA)

New medications to treat HIV have changed this infection from a deadly disease into a chronic condition. Therefore, people infected with HIV (PHAs) are living longer, healthier lives and, like everyone else, are seeking surgery for varied conditions. At present, it is not known how many PHAs in Ontario undergo surgery, what types of procedures are commonly being performed or the associated post-operative outcomes. The purpose of this study is to describe the incidence of major surgical procedures post advent of antiretroviral medication and determine whether postoperative outcomes are similar to those of HIV uninfected people. The Investigators hypothesize that an increasing number of PHAs are undergoing major surgical procedures with similar outcomes when matched with HIV uninfected patients.



Dr. N. Poonai
London Health Sciences Centre

Intranasal ketamine for procedural sedation in children: a randomized controlled non-inferiority trial

Sedating children for painful procedures, termed procedural sedation, is commonly performed in the emergency department (ED). Procedural sedation is almost universally performed by giving anesthetic drugs intravenously (IV). Due to its safety profile and efficacy, the most common drug for sedation in children is ketamine. Unfortunately, inserting an IV in a child is time-consuming, a strain on nursing resources, an infection risk, and most importantly, very painful. Evidence suggests children view an IV as one of the most painful parts of their hospital experience. Furthermore, nurses in general EDs (that primarily treat adults) have limited experience placing an IV in a child, further straining resources and causing distress to the family. Although ketamine is necessary for effective sedation, it can also be delivered through the nose or intranasally (IN). The Investigators' two-year project will evaluate if IN ketamine is effective to sedate children undergoing painful procedures. If the Investigators show that IN ketamine is less time-consuming, less skill-dependent, less painful, but just as effective for anesthesia, it could radically change the way we sedate children in the ED. More importantly, it will enable health care workers at both adult and paediatric EDs to adopt a pain-free and less resource-intensive approach to caring for children with injuries.



Dr. H. Retrouvey*
Dr. T. Zhong

London Health Sciences Centre

Understanding and Reducing Barriers to Postmastectomy Breast Reconstruction in Ontario

Breast cancer is the most common cancer in women affecting 1 in 9 Canadian women during their lifetime. Treatment involves mastectomy (surgical removal of one or both breasts), which can lead to body image issues and a decline in quality of life. Breast reconstruction (BR) can be offered to breast cancer patients after mastectomy and aims to surgically restore the breast form. BR may provide long-term quality of life improvements as well as psychological benefits for patients whom choose this option. Despite these potential benefits, BR remains underused in Ontario as it fails to be consistently integrated as part of the treatment of breast cancer patients.

The Investigators performed a systematic literature review and found that patient factors such as increased age and non-Caucasian race; tumor characteristics such as larger tumours; as well as negative physician perceptions of BR were associated with low rates of BR. Canadian studies highlighted a significant problem, that access to BR in Ontario was not universal. Additionally, studies failed to explain how these factors can lead to low rates of BR. Meaningful discussions with patients, clinicians and hospital administrators are needed to increase our understanding of the relationship between these different barriers and poor access to BR in Ontario. In this study, the Investigators will first conduct interviews to increase our understanding of the local barriers to access to BR in Ontario, and then use this knowledge to design interventions that target these barriers and aim to improve access to BR in Ontario. The Investigators' ultimate goal is to ensure that all breast cancer patients whom wish to have BR have access to this surgical procedure, as dictated by the principles of the Canadian universal health act.



Dr. E. Schemitsch
Dr. D.M. McKee

London Health Sciences Centre

The DECIPHER Study: Determinants of Function and Clinically Important Outcomes following Proximal Humerus Fractures in the Elder Population: A National Cohort

Shoulder fractures are increasingly common in older adults, and result in considerable limitations in function and quality of life. Unfortunately, the best way to treat shoulder fractures is currently one of the most debated areas of orthopaedic trauma research. Existing clinical studies comparing various methods of surgical and non-surgical management have reported conflicting results. These studies have had limited numbers of patients, involved single centres, and used inconsistent treatment methods and inclusion/exclusion criteria. Therefore, there is insufficient evidence supporting any one treatment type, and a poor understanding of what factors influence the outcomes that are important to patients, making decisions regarding treatment difficult.

The Investigators propose to establish DECIPHER, the first nation-wide, multicentre observational study with at least 650 fully characterized patients with the ultimate goal of determining what factors influence patient important outcomes. Additionally, we will answer important questions concerning health service utilization, whether treatment strategies should be different in older patients (70 years and older) or in patients with more associated medical disorders, and the best method of rehabilitation following treatment.

Patients 50 and older with shoulder fractures will be recruited from approximately 11 centres across Canada and followed for one year, during which time patient function and quality of life centered outcome measures will be collected at regular intervals. A cost analysis will be conducted to determine the impact of treatment type on patient and healthcare system costs. The information collected through DECIPHER will not only help guide treatment decisions, but serve as a stepping stone for future studies to determine the best treatment strategy for managing these difficult injuries.



Dr. S. Schuh
Dr. Y. Finkelstein

Hospital for Sick Children

Suctioning of NOse Therapy (SNOT) versus Usual Home Care in Bronchiolitis - a Randomized Clinical Trial

Bronchiolitis is a very common viral respiratory tract infection in young infants, characterized by nose congestion, cough, breathing and feeding difficulties. Since there are no useful medications to treat this disease, all we have to offer for infants with bronchiolitis is hydration and oxygen supplementation. Congested nose is a major cause of poor feeding and breathing discomfort in bronchiolitis, which frequently leads to hospitalization. Suctioning of nose represents the most commonly used treatment for congestion. However, no previous studies have examined the benefit of nasal suctioning in bronchiolitis and we therefore do not know if this treatment works. Experts call for examination of the benefit of this therapy. Since some children are uncomfortable while having their nose suctioned, it is important to know whether nasal suctioning is beneficial or not.

In this study we will examine if infants with bronchiolitis who receive boosted nasal suctioning prior to feeding (after discharge home from the emergency department [ED]) have a lower chance of treatment failure compared to infants getting usual care.

This is a randomized single-blind study in 2 Canadian pediatric EDs of 372 previously healthy infants 1-12 months old with bronchiolitis. Following discharge home from the ED, eligible infants with reported abnormal feeding and observed breathing distress will receive either enhanced nose suctioning prior to feeds using a commercially-available suctioning device or usual care, for the next 7 days. The main outcome will be treatment failure, i.e. any medical visit for bronchiolitis (parent- or physician-initiated medical visits or hospital admissions) within 7 days of discharge home. The Investigators shall also measure the infant's level of feeding and sleeping adequacy at 72 hours and on day 7 after discharge.

The Investigators estimate that boosted nasal suctioning will result in fewer medical visits which will in turn decrease the burden of bronchiolitis care on the caretakers and the health-care system, with immediate impact on clinical practice.



Dr. D. Seitz
Queen's University

Comparative Safety and Efficacy of Antipsychotic Medications in Late-life Psychotic Disorders: A Population-Based Study from Ontario

With the aging of our population, there are increasing numbers of older adults living with schizophrenia and related psychotic disorders. Antipsychotic medications are first-line, Health Canada approved medications for the long-term treatment of psychotic disorders in all age groups. However, very little is known about the types of antipsychotics medications prescribed to older adults with psychotic disorders (those aged 65 and older). There are also few large-scale studies evaluating the safety of antipsychotics in older adults with psychotic disorders or whether there are differences in the effectiveness of different antipsychotics in this population. In the current study, we propose to study the patterns of antipsychotic use among older adults with psychotic disorders in Ontario and evaluate the safety and effectiveness of different classes of antipsychotic medications in this population. This study will provide new information comparing the safety and efficacy of antipsychotics in late-life psychotic disorders using a large real-world population of older adults. Information learned from this study will help guide safe and effective prescribing for the growing population of older adults with psychotic disorders in Ontario and worldwide.



Dr. S. Shaikh*
Dr. T. Karachi

McMaster University

End of Life Skills & Professionalism for Critical Care Residents in Training - ESPRIT Study

Palliative and End-of-Life (EOL) care, and care of the potential organ donor, are essential components of delivering high-quality care in the ICU. CCM subspecialty residents play a crucial role in providing this care to patients and their families. To date, there has been no report of the current landscape of EOL care education for CCM subspecialty residents in Canada. The Investigators' dynamic team is composed of residents, research trainees, intensivists, palliative care physicians, and internists, and includes some national leaders in research methodology, palliative care, and educational development. Members of the team have also been working with provincial organizations such as the Trillium Gift of Life Network (TGLN) on developing educational tools addressing organ donation for CCM residents. With the help of collaborators across Ontario, the Investigators have begun developing survey instruments for CCM subspecialty residents and program directors that will allow us to evaluate the current structure of EOL training for all CCM residents in Canada. The Investigators will soon be ready for instrument testing, including piloting, clinical sensitivity testing, and reliability testing. With support from PSI, the Investigators will administer this survey to residents and program directors at all 5 CCM residency programs in Ontario. They will also use local funds from the McMaster CCM Residency Program to administer this survey in other provinces. By gaining an understanding of the current state of EOL care teaching in CCM subspecialty programs, first in Ontario, then nationwide, the ESPRIT Study will facilitate the informed evolution of a comprehensive integrated EOL curriculum in Canada.



Dr. V. Siu
London Health Sciences Centre

Effects of histidine therapy on hearing and vision in children with HARS syndrome

HARS syndrome is a progressive degenerative disease affecting eyesight and hearing. It is caused by a mutation in the HARS gene which codes for an enzyme involved in protein synthesis. It has been exclusively found in the Old Order Amish communities in Southwestern Ontario and in Pennsylvania. Children with this disorder initially have normal vision and hearing, but with a febrile illness, they can have a sudden loss of vision and hearing, as well as visual hallucinations. In more severe cases, fluid accumulates in the lungs which can cause a drop in oxygen levels and sometimes death. There is currently no specific treatment for this disease. Anecdotal evidence suggests that administration of L-histidine may lead to an improvement in vision; however, no baseline objective measurements of vision were conducted prior to this treatment. The Investigators have designed a project in which histidine will be given to children with HARS for 2 years. The Investigators will monitor vision, hearing and bloodwork to determine any changes during the treatment course. Results from this project may pave the way for a standard of care for these patients.



Dr. A. Strafella
University Health Network

Imaging synaptic density in Parkinsonisms with [11C]UCB-J PET

To date most of the imaging studies with Positron Emission Tomography (PET) in parkinsonism have focused on investigating dopaminergic neural changes. This pilot study intends to shift the focus from receptor to synaptic density, as a proxy of synaptic pruning in-vivo, to quantify neurodegenerative changes at the cortical and subcortical level in atypical forms of parkinsonisms, i.e. Progressive Supranuclear Palsy and Multiple System Atrophy, as compared to classic form of Parkinson's Disease. We will use the novel PET radioligand, i.e. [11C]UCB-J, for imaging synaptic vesicle glycoprotein 2A (SV2A) as in-vivo proxy of synaptic density.This newly developed PET biomarker if successful may be useful as i) a early diagnostic tool, ii) an indicator of disease severity and progression, iii) an assessment tool for atypical parkinsonisms and their treatments.

October 1 to December 31, 2017



Dr. A. Mayo
Dr. S. Hitzig

Sunnybrook Health Sciences Centre

Health and Quality of Life Outcomes Post-Amputation in Ontario

As the population ages, the number of people with dysvascular (diabetes and/or vascular disease related) lower-limb amputation (LLA) will continue to rise as diabetes becomes more common. Most of the research to date has focused on the short-term outcomes related to function and health following in-patient rehabilitation for LLA but very little is known about long-term effects of living with LLA. To better understand the physical, psychological and social outcomes in people living with LLA in the community, the proposed project aims to conduct a multi-phase study across three sites that collect: 1) telephone survey data on the health and wellbeing of 300 adults with dysvascular LLA living in Ontario; 2) in-depth interview data to gain the perspectives of 36 people living with LLA in the community ; and 3) multi-method data how people with LLA in the community are using the health care system to maintain their health and wellbeing. The findings from this study will provide details on the burden of living with dysvascular LLA at the individual and societal level, which can be used to inform clinical practice and policies to help people aging with dysvascular LLA in the community optimize their health and wellbeing.



Dr. P. Murphy*
Dr. K. Vogt

London Health Sciences Centre

Impact of Surgeon Factors on the Management and Outcomes of Acute Appendicitis

The purpose of this project is to characterize the modern management of acute appendicitis in Ontario and the impact of surgeon factors on complications. Removal of the appendix, or appendectomy, is one of the most common surgical conditions and will affect 1 in 12 people worldwide and in Ontario. Appendectomy can be performed with the traditional open approach or through a minimally invasive approach using laparoscopy. The reported benefits of laparoscopy include lower complication rate, reduced post-operative pain and shorter length of stay. Despite this, the use of the open approach for appendectomies remains high in Canada; approximately 40% of appendectomies are performed open. There are a number of variables that may influence a patient's complication rate. Patient factors such as age, sex and co-morbidities certainly influence complication rates. This study will uniquely be able to study surgeon characteristics such as age, years in practice and choice of surgical approach (laparoscopic or open) and the impact on complication rates. The choice of performing a laparoscopic or open procedure largely is based on the surgeon rather than the patient. Given the nearly 100% transition to laparoscopic surgery for other operations, such as cholecystectomy, the Investigators aim to determine surgeon characteristics on the use of surgical approach for appendectomy. The Investigators hypothesize that older surgeons are performing more open appendectomies compared to younger surgeons. The transition to laparoscopy for most practicing surgeons occurred around his or her mid-carrier. Further, the benefits of a laparoscopic approach for appendectomy are not as profound compared to cholecystectomy which may explain the reduced transition for older surgeons. The Investigators also hypothesize that the complication rate for the open approach is higher than that of laparoscopy even when open surgery is performed by surgeons who prefer the open approach. The study will use the Institute for Clinical Evaluative Sciences (ICES) administrative data holdings from 2005-2015. This large dataset will allow the Investigators to determine the influence of surgeon characteristics on complication rate, in particular the surgeon's preference of laparoscopy or open approaches. They will also determine the impact of on surgical preference on other secondary outcomes, such as length of stay and readmission rates. The last characterization of appendicitis in Ontario was nearly 15 years ago. This study will provide the largest definitive report on the modern management of appendicitis and guide on-going management in Ontario and Canada.



Dr. A. Petrosoniak
St. Michael's Hospital

Deliberate practice and mastery learning: a multi-centre randomized study for technical skills training in medicine

Simulation-based training is now a cornerstone in residency medical education. Multiple studies show simulation training is superior to traditional teaching methods (e.g. lectures) for technical skill acquisition. Highly structured practice, a training strategy used increasingly in simulation training, provides systematic and focused feedback from expert instructors. There is little evidence, however, demonstrating its superiority over less resource intensive approaches such as trainee-guided practice, where the learner practices a skill and requests instructor feedback only when they feel it is required. This less resource intensive approach is more cost effective and requires fewer instructors. Given the balance between resources and learning outcomes, an improved understanding of how to design efficient simulation-based training that maximizes learning is required. This study compares highly structured practice with learner-guided practice for skill performance of a life-saving emergency airway procedure, a bougie-assisted cricothyroidotmy. A multi-centre, randomized study will be conducted at four Canadian residency programs with approximately 100 residents assigned to one of the two practice methods. Skill performance will be evaluated, before, immediately after practice and 6 months later. Performance of each group will be compared to assess whether the type of practice impacts performance and skill retention. This study will have important implications for residency training across the country as it will aid medical educators in their design of simulation-based practice sessions. Better residency training ultimately translates to patients through better outcomes and improved patient safety. From a policy and funding perspective, these study results will guide resource allocation for skills training and inform future curricular designs.



Dr. M. Selzner
University Health Network

Normothermic Ex Vivo Kidney Perfusion for the Storage, Assessment, and Repair of Human Kidney Grafts Prior to Transplantation

Kidney transplantation offers improved survival and a better quality of life for patients with end stage renal failure. Unfortunately many more patients are waiting for kidney transplantation then organs are available. As a result patients with renal failure have to wait for several years until an organ becomes available. This organ shortage has triggered interest in the use of grafts obtained from older donors or donors with cardiac arrest (marginal grafts) for kidney transplantation. To allow transplantation kidneys have to be stored for several hours cold without oxygen to allow for transportation from the donor hospital to the transplant center and for recipient preparation. Unfortunately marginal grafts do not tolerate cold storage well and often develop poor function after transplantation. The Investigators developed a new technique of kidney storage, which uses warm kidney perfusion outside the body with oxygen, blood cells and nutrition. In several animals studies using pig kidney transplantation we determined that warm perfused kidney storage improves kidney function and reduces kidney injury resulting in higher quality grafts. The Investigators propose in this application to translate the animal findings into a clinical trial to use warm perfused kidney storage for human kidney transplantation.



Dr. R. Zemek
Dr. A. Ledoux

Children's Hospital of Eastern Ontario

Pediatric Concussion Assessment of Rest and Extertion+MRI

Concussion in children and youth is a common public health concern. Children are not only at higher risk of sustaining concussions than adults, but recovery also takes longer. Physical symptoms (such as headache or dizziness), concentration problems, and emotional changes are common following concussions. One third of children with concussion continue to experience symptoms for more than one month, a condition known as Persistent Post-Concussive Symptoms (PPCS). PPCS has been shown to lower quality of life, especially school quality of life. Further, PPCS symptoms may impede children from doing the activities that they love, such as competing in team sports or attending social gatherings with friends. To prevent PPCS, it was thought that the best recovery plan was to rest both mentally and physically until children became symptom-free. However, recent research suggests that too much rest may cause more harm than good. Determining the ideal balance of rest and physical activity may help decrease the chance of having PPCS. Rather than solely relying on patient self-report to determine recovery, studies that also include objective measures of recovery are urgently needed. The proposed study (PedCARE+MRI) will combine state-of-the-art MRI scans (advanced neuroimaging) with patient self-report to determine whether restarting physical activity at 3-days following a concussion results in both faster return back to normal brain function (by measuring brain blood flow on advanced MRI scan) and lower risk of PPCS (by self-report) as compared to complete resting until symptom-free.