Foundation Funded Projects for 2014
Dr. M. Barua
Dr. D. Cattran
Toronto General Hospital
Defining the genetic epidemiology of sporadic focal and segmental glomerulosclerosis
Focal and segmental glomerulosclerosis (FSGS) is an important clinical syndrome of diverse causes and accounts for 5% of end-stage renal disease (ESRD) in Canada. It affects the filters of the kidney and can be effectively treated with steroids in approximately 40% of cases. In cases of steroid-resistant FSGS, disease is caused by mutations of genes (e.g. ACTN4, INF2) within a highly specialized cell of the kidney filter called the podocyte. A significant proportion of individuals resistant to steroid therapy will develop ESRD within 5-7 years.
Recent advances of a new technology called next-generation sequencing have provided a revolutionary tool for disease gene sequencing that bypasses the bottleneck of gene-by-gene mutation screening at substantially reduced costs. Using this new sequencing technology, the investigators seek to develop a test that will screen many known FSGS genes in a single sample at economic costs. The researchers further seek to identify the most common FSGS genes and to identify additional causative factors underlying steroid-resistant FSGS.
These goals will serve to improve the ability to diagnose and offer prognostic information while also providing the foundation for developing better mechanism-based therapies.
Dr. S.E. Card
Dr. B.C. Dickson
Mount Sinai Hospital
Assessment of sex steroid hormone receptor expression in liposarcoma: a potential therapeutic target
Liposarcoma represents the most common soft tissue sarcoma. For patients with advanced disease, there are limited treatment options available. The objective of this project is to determine whether liposarcoma expresses hormone receptors.
The researchers plan to construct tissue microarrays representing each of the variants of liposarcoma. Using immunohistochemistry, tumours will be analyzed for the expression of androgen receptor, estrogen receptor and progesterone receptor. If the investigators are successful in demonstrating the presence of hormone receptors in these tumours, this would represent a new and potentially important therapeutic target in liposarcoma.
Dr. C.T. Chan
Dr. C. Lok
University Health Network
The impact of exercise on vascular remodeling, arteriovenous fistula creation and use in patients with chronic kidney disease: a randomized controlled trial
Chronic kidney disease (CKD) patients often require life-sustaining hemodialysis. To enable hemodialysis blood must be removed from the body, preferably via a surgically created forearm conduit, called an arteriovenous fistula (fistula). Fistulas are the preferred conduit due to their low complications, however in some patients inadequate blood flow through the fistula causes the fistula to fail after surgery, meaning it cannot be used for dialysis.
Exercising the forearm before surgery may make blood vessels bigger and healthier, simplifying surgery, improving blood flow and reducing chances of fistula failure; however exercise is not routinely prescribed before surgery because the benefit is unclear. This study aims to evaluate whether progressive forearm exercise prior to fistula creation will increase the size and health of the blood vessels, enhance fistula blood flow after surgery (assessed by ultrasound), and reduce fistula failure.
The intervention is a personalized progressive exercise protocol (30 minutes daily for eight weeks) and will consider the quality (health) of patients’ blood vessels at study entry, assess fistula blood flow adequacy for hemodialysis, and determine the proportion of fistulae successfully used for dialysis. This is the first study to determine the clinical benefit of forearm exercise for fistula creation and use.
Dr. K.A. Crawford
Dr. N. Dudek
University of Ottawa
Assessing clinical supervisors’ assessments - what makes them better?
The evaluation of medical students and resident physicians throughout their training is essential to ensure that they ultimately become competent and safe independently practicing physicians. In-training evaluation (ITE) by physician preceptors is a common assessment process. This assessment is recorded on an In-Training Evaluation Report (ITER). Unfortunately, ITERs are often poorly completed, particularly in the case of the poorly performing resident.
There is evidence that clinical supervisors lack knowledge regarding what to document on ITERs and that is in part responsible for the failure to report unsatisfactory clinical performance. Faculty Development (FD) programs have been shown to improve the quality of ITER completion by physician preceptors. FD programs generally attract motivated volunteers and recruiting those physician preceptors who are unmotivated to improve is a challenge.
This study will investigate whether clinical supervisors will improve their ITER quality based on feedback regardless of their motivation to do so and, if an improvement in ITER quality is found, whether they can maintain this improvement without ongoing feedback.
Dr. S. Singwi
Headwaters Health Care Centre
Knowledge extraction from a community hospital EHR to improve anesthetic patient care
The goal of any health care quality project is to improve patient outcomes, decrease cost, improve efficiencies and help with clinical decision making.
This proposal will use the principles of “Big Data” and the EHR (Electronic Health Record) to implement quality care for the anesthetic patient. In addition this project will serve as a proof of concept for other applications of big data in our hospital.
Dr. J.G. van Dyk
Dr. P.T. Church
Sunnybrook Health Sciences Centre
The predictive validity of the Assessment of the Quality of General Movements for identification of long-term neurodevelopmental outcome in preterm infants
Preterm birth (birth prior to 37 completed weeks of gestation) is on the rise and is associated with an increased risk of developmental disability. Early prediction of disability is important because early therapeutic interventions (such as accommodations, occupational and physiotherapy, family training and social services) have been shown to improve developmental outcomes for individuals in school and social environments. Historically, there have not been adequate clinical tools that can accurately identify those at risk of developmental problems.
Recently, a tool has been proposed that offers a reliable and accurate means to identify those infants at risk for future developmental disability, particularly cerebral palsy (CP). The Assessment of the Quality of General Movements (AQGM) is an observational assessment of infants’ whole body movements where the way an infant explores movement patterns in time and space reflects the underlying integrity of the nervous system. The AQGM offers a cost effective, minimally disruptive and accessible tool. In this study, investigators will evaluate video recorded AQGMs obtained at two stages of infant development and determine if the trajectory of the patterns (whether quality of movement normalizes over a specified period of time) further assists with identification of future disability.
Dr. L.M. Ward
University of Ottawa
Bone fragility in boys with Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a disorder affecting boys that is associated with progressive loss of muscle function, including ambulation. There is no cure for DMD at the present time; however glucocorticoids are used long-term to prolong ambulation and improve cardiorespiratory function. Bone fragility (osteoporosis) is debilitating in this setting, manifesting as long bone and vertebral fractures, back pain and premature loss of ambulation. At the same time, there is a lack of knowledge on the clinical predictors of long bone and vertebral fractures, as well as strategies for effective osteoporosis prevention in DMD.
The purpose of this research program is to lay the foundation to address this care gap. The researchers will conduct a national, multi-centre study to determine when and how often fractures occur in pediatric DMD. The risk factors for bone fragility in this population will also be studied in detail, including the use of novel biomarkers to predict fractures and low bone density.
The results of this program of research will allow us to better understand the mechanisms of bone fragility in this condition, create knowledge that is required for the development of much-needed osteoporosis diagnosis and monitoring guidelines, and inform the design of a large-scale trial to prevent the debilitating consequences of osteoporosis in boys with DMD.
Dr. C. Yamashita
Dr. R. Veldhuizen
Antimicrobial peptide fortified surfactant for the treatment of cystic fibrosis
Cystic fibrosis (CF) is a common hereditary disease characterized by recurrent lung infections and a progressive decline in lung function. The administration of inhaled and systemic antibiotics in patients with CF has been the main therapy for preventing and treating bacterial lung infections. Unfortunately, due to this frequent use of antibiotics, drug-resistant strains of organisms are commonly found in patients with CF and represent a predictor of poor outcomes; therefore the development of novel therapeutic agents capable of treating lung infections associated with CF is urgently needed.
Antimicrobial peptides have been shown to exhibit potent antibacterial activity and are largely free of traditional antibiotic resistance patterns. Pulmonary surfactant represents a lipid protein mixture that has excellent spreading properties that could facilitate the delivery of medications to the airways when delivered directly to the lung; therefore the objective of this proposal will be to determine the efficacy of a novel antimicrobial peptide fortified surfactant compound for the treatment of CF.
In this study, the activity of this compound will be tested against bacteria identified in human CF sputum samples. These studies will have the potential to lead to the development of a novel therapy for patients with CF.
Dr. M.G. Fehlings
University Health Network
Preventing neurological decline in cervical spondylotic myelopathy with intravenous IgG
Previous PSI funding allowed for the determination of the effectiveness of the immune modulating therapeutic IgG for the treatment of acute traumatic spinal cord injury (SCI). Due to the huge success of this work, which culminated in a U.S. patent and collaboration with a pharmaceutical company for end stage pre-clinical work, similar conditions have been identified that could benefit from this treatment.
One such indication is cervical spondylotic myelopathy (CSM). CSM results from age-related progressive compression of the spinal cord and is the most common form of spinal cord impairment in the world. Despite the success of surgical decompression, patients are often left with severe neurological deficits. Surgical decompression, while beneficial, can be associated with certain risks and negative events.
It is hoped this study will show that IgG can (i) protect the spinal cord during chronic spinal cord compression (CSM) and (ii) protect the spinal cord following surgical decompression intervention for CSM.
Dr. L. Lapointe-Shaw
Dr. J. Feld
University Health Network
Diagnosis and management of hepatitis B and hepatitis C infection in Ontario
Hepatitis B and C together are the cause of significant morbidity and mortality worldwide. Late diagnosis is a barrier to receiving effective therapies and appropriate monitoring.
This Ontario population-based study will use linked laboratory, administrative and clinical datasets for patients diagnosed with Hepatitis B and/or C. Time from diagnosis to complication will be determined and will be compared to the known natural history of infection, as well as clinical data from the Toronto Western Hospital Liver Clinic. This will allow for the identification of whether patients are diagnosed late in their clinical course, when cirrhosis and other complications have already developed. Linked laboratory and health administrative health data will be used to define the healthcare course of patients following diagnosis. This will include testing for co-infection, assessment by specialist physicians, treatment with effective agents and monitoring for complications.
The goal of this proposed study is to identify opportunities for improvement along the entire care trajectory of patients with hepatitis B and C; further, the findings will inform policymaker decision-making around screening practices and healthcare organization and delivery for patients with viral hepatitis.
Dr. Y. Leong
Dr. H.P. Drutz
Mount Sinai Hospital
A randomized double-blinded trial comparing fesoterodine to desmopressin in the treatment of severe nocturia in women aged 65 and older
Nocturia, or voiding at night, is an extremely troublesome symptom which is highly prevalent in the elderly. Desmopressin is a treatment for nocturia but it can result in hyponatremia (low blood sodium), particularly in those aged 65 and older. Fesoterodine is used for the treatment of overactive bladder (OAB) and recent trials showed it was effective in reducing nocturia.
The aim of this study is to answer the following: In women 65 and older with severe nocturia, is Fesoterodine more effective than Desmopressin in reducing the number of night time voids? Does Fesoterodine have a better side effect profile compared to Desmopressin? The study design is a 12-week randomized double-blinded trial of Fesoterodine and Desmopressin in the treatment of severe nocturia in women aged 65 and older. This will be conducted at the Urogynecology Unit at Mount Sinai Hospital (MSH) and Baycrest. A 3 day voiding diary and Nocturia, Nocturnal Enuresis and Sleep-interruption Questionnaire (NNES-Q) will be completed at baseline and at week 12.
The primary outcome will be the number of night time voids in the Fesoterodine group compared to the Desmopressin group, 12 weeks after starting treatment. Secondary outcomes include changes in the NNES-Q scores and the safety of each medication.
Dr. T. Marras
University Health Network
Risk of pulmonary nontuberculous mycobacterial disease associated with inhaled corticosteroids in Ontario
Inhaled steroids are widely used medications for treating chronic obstructive pulmonary disease (COPD) and asthma, two very common lung conditions. Recent studies showed that inhaled steroids increase the risk of pneumonia and tuberculosis (TB) in people with COPD. It is unclear if inhaled steroids also increase the risk of nontuberculous mycobacteria (NTM) lung infections. NTM cause serious, chronic, and difficult to treat lung infections, which are more common in Ontario than TB.
In this study, the researchers will determine if using inhaled steroids increases the risk of NTM lung infections in older Ontarians with COPD and asthma, and measure this risk. Information from Ontario’s main NTM laboratory (results from Ontarians with NTM germs identified), and the Ontario Health Insurance Plan (OHIP; for inhaled steroid prescription records) will be combined. To learn if inhaled steroids are a risk factor for NTM lung infections, rates of NTM lung infection between Ontarians who do versus Ontarians who do not use inhaled steroids will be compared.
This project will be the largest study of this problem and the first Canadian study. The results will help doctors make better decisions about screening and treatment for NTM when prescribing inhaled steroids, and help patients better understand potential harms from these drugs.
Dr. D.R. Ricciuto
Trends in C. difficile infection frequency, severity and length of stay after implementation of an antimicrobial stewardship program and C. difficile toolkit at a large, community hospital
The aim of this study is to determine the impact of a multifaceted intervention to prevent and manage C. difficile infection (CDI). Specifically, the researchers hypothesize that: 1) the intervention resulted in a significant decline in the overall rate of hospital-acquired CDI in a large, community hospital; and, 2) the severity, length of stay, requirement for colectomy and mortality of patients diagnosed with hospital-acquired CDI declined after the intervention.
Dr. S. Schuh
Hospital for Sick Children
Inhaled magnesium in refractory pediatric acute asthma (MAGNUM PA Trial)
While bronchodilators and steroids reduce hospitalizations in pediatric acute asthma, a third of patients remain in breathing distress, accounting for 84% of asthma hospitalizations. Finding safe, non-invasive and effective strategies to treat this group would further decrease hospitalizations and health care costs. Although intravenous magnesium (IV Mg) reduces hospitalizations in children resistant to standard therapy, nebulized Mg is non-invasive and likely safer.
The purpose of this study is to examine if children with acute asthma in moderate to severe respiratory distress despite maximized therapy have a reduction in hospitalizations after nebulized Mg with salbutamol versus salbutamol only. This is a randomized double-blind trial in 7 Canadian pediatric Emergency Departments of 816 previously healthy children 2-17 years of age with acute asthma. Following oral corticosteroids and bronchodilator treatments, eligible children with a PRAM score of ≥ 5/12 points will receive three treatments of nebulized salbutamol with Mg or placebo via a pre-tested Pockethaler nebulizer.
The main outcome will be hospitalization within 24 hours for persistent respiratory distress or supplemental oxygen. It is anticipated that addition of nebulized Mg will decrease hospitalizations in asthmatic children not responding to optimized initial treatment, with a major impact on current clinical practice and care of this high-risk population.
Dr. C. Smyth
Dr. P. Poulin
University of Ottawa
Evaluation of an interdisciplinary complex pain management program linked to primary care to improve clinical outcomes and reduce health care utilization among patients with chronic pain and frequent emergency department visits
Chronic pain (CP) is a common illness with devastating impacts. Lack of community care and limited access to expertise can lead to frequent and costly emergency department (ED) visits and hospital admissions. More than 12% of all ED visits are for CP; clearly, patient needs are not being met by primary care physicians (PCP) or hospitals. Some patients with CP visit the ED more than 12 times per year (high frequency users; CP-HFU) and are admitted to hospital for long periods.
This study will test whether pain management provided by a specialized pain team, including the patient’s PCP, leads to improved pain control and function in the community while reducing their use of acute care resources such as the ED. The study will compare pain, disability, ED visits and days spent in hospital in CP-HFU that have immediate access to an Interdisciplinary Complex Pain Management Program (ICPMP) to those with a 3-month wait after referral. ICPMP will be evaluated from the point of view of all stakeholders.
It is expected that CP-HFU will improve in many domains. Savings through reduced ED visits and hospital admissions will recoup the cost of ICPMP resulting in improved health care value.
Dr. W. Alhazzani
REVISE: Re-evaluating the Inhibition of Stress Erosions: gastrointestinal bleeding prophylaxis in ICU
This study of critically ill patients will examine the effects of acid suppression on bleeding from the stomach. Acid suppression is prescribed for almost all critically ill patients based on research done 10-20 years ago showing a clear reduction in bleeding; however today, grave concerns exist about whether these drugs still prevent bleeding, whether they are cost-ineffective, and whether they cause harm such as lung infection (pneumonia), or serious bowel infection (Clostridium difficile).
The investigators will enroll patients who are connected to a breathing machine. The patients will be divided into 2 groups. The first will receive a medication (pantoprazole) that reduces the acid levels in the stomach; the second group will receive an identical medication with no effect on acid levels. This approach will keep everyone unaware of the treatment received, to avoid inaccurate results when examining the outcomes.
In this pilot trial, the researchers will gain crucial experience obtaining informed consent, enrolling patients efficiently, and ensuring they receive their study drug. Lessons learned from this feasibility study will help to prepare a large trial to evaluate whether widespread acid suppression in critically ill patients is beneficial, has no effect, or is harmful.
Dr. A. Ali
Hospital for Sick Children
Feasibility of specular microscopy in a pediatric population
Corneal endothelial cells are vital to maintain clarity of the cornea and preserve normal vision. As they do not proliferate, they cannot regenerate in response to damage from disease and from surgery. Their loss eventually can lead to edema and severe vision impairment, with greatest impact in childhood when the visual system is immature. Imaging of the corneal endothelial cell layer using specular microscopy first became available in 1976. Then and now, it requires immobility of the eye during measurement and therefore cannot be performed in young children. As such, there is a paucity of in vivo studies investigating the corneal endothelium in this population.
This team has developed a technique to image children under general anesthesia at any age. This will enable for the first time the establishment of normal ranges for endothelial cell density in children under the age of 5 and to determine the endothelial changes that occur in a variety of ocular disorders and following intraocular surgery.
This project will help define the natural history of the developing endothelium, improve diagnostic tools for children with endothelial diseases and potentially find ways to prevent corneal blindness and therefore reduce the need for corneal transplants in later life.
Dr. E. Belley-Côté
Dr. D. Cook
Prognostic value of elevated troponins in critical illness study (PRO-TROPICS): a pilot study
Troponin levels as measured in the blood are markers of heart injury. Critically ill patients in the intensive care unit (ICU) frequently have increased troponin levels. Elevated troponin levels are needed as proof of a heart attack. In critically ill patients, telling the difference between an increase in troponin from a true heart attack is difficult. Many critically ill patients with an increased troponin level do meet the criteria for a heart attack, while some do not. Troponin elevations seem to be associated with an increased risk of death in the ICU whether patients are actually diagnosed with heart attack or not. Doctors do not know whether and how to treat these patients with elevated troponin levels.
The investigators will perform a 1-month pilot cohort study of troponin screening in 2 Ontario ICUs. Our objectives are to ensure we can successfully enroll patients, collect data, and obtain consent from family members for the troponin tests and electrocardiograms. The overall goal of this pilot study is to evaluate the ability to perform a larger study, which will determine the frequency, consequences, and treatment of troponin elevations in the ICU.
Dr. C.S.Y. Cheung
Dr. W. Lam
University Health Network
Progression of geographic atrophy and intravitreal injections of ranibizumab among patients treated for age-related macular degeneration
Age-related macular degeneration (AMD) affects central vision regions in people 60 years or older. There are two forms of AMD – dry and wet. The standard of care for wet AMD is monthly intraocular injections; however no definite treatment is available for dry AMD. A severe form of dry AMD called geographic atrophy (GA) also has adverse effects on vision as it extends to the central vision. Studies to date suggest worsening of GA, particularly enlargement of GA area in patients receiving intraocular injections compared to those who have not received any injections.
The primary objective of this study is to evaluate if there is worsening of GA secondary to intraocular injections. Patients who have GA will be recruited into our study and be followed for 2 years, with follow-up every 6 months. Retinal photographs for GA patients who are receiving intraocular injections will be compared to those who are not. Area of GA on retinal photographs will be traced and computed by mathematical software. GA area enlargement will be assessed in relation to the numbers of injections received. The proportion of central GA will also be compared between patients receiving injections against those who have not received any injection.
Dr. N. Cullen
Dr. A. Colantonio
University Health Network
Hypoxic-ischemic service utilization
Hypoxic-ischemic brain injury (HIBI) refers to brain damage from oxygen reduction or diminished blood supply. Common causes of HIBI include cardiac arrest, near drowning, carbon monoxide poisoning, and asphyxia. It is a devastating injury that leads to significant long-term disability. Currently, there are no population-based data on the demographic profile of patients with HIBI or their path through the healthcare system. This makes it difficult to appropriately plan health services that tailor to this group of patients.
The proposed study will use administrative data to determine the clinical profile and health service utilization of Ontario adults with a diagnosis of HIBI. Patients with HIBI will be identified in four main healthcare settings (emergency department, acute care hospital, rehabilitation, and outpatient physician visits). Discharge destination from each setting will be used to track the patient pathway through the healthcare system. Other important measures of service utilization include length of stay in each health care setting and number/type of outpatient physician visits in the first year following injury.
Findings from this project can assist planning of services across the continuum of care for this population, inform public policy, and help direct healthcare costs to best address the needs of patients with HIBI.
Dr. T.P. Grantcharov
St. Michael's Hospital
Assessing personality traits of surgical trainees to predict non-technical and crisis management skills in the operating room
Non-technical skills such as teamwork, communication and leadership are competencies required of surgeons that have been shown to be critical for patient safety in the operating room. Despite the demonstrated importance, however, non-technical skills are still infrequently addressed in surgical residency programs, which is in part owing to the substantial cost and expenditure of time associated with designated training and assessment of these competencies. In addition, studies have shown pronounced inter-individual differences in “innate” non-technical skills, challenging the concept of a “one-fits-all” approach to training.
If trainees’ innate non-technical skills could be predicted at the start of surgical residency, training could be tailored to individual needs. The proposed study is based on the hypothesis that certain measurable personality traits can predict a surgeon’s non-technical skills. To test this hypothesis, video recordings of surgical residents in simulated crisis scenarios will be reviewed by trained observers and scored on a validated rating framework of non-technical skills. Non-technical skills scores of the participants will be correlated with the participants’ personality scores on five specific domains.
If personality traits can predict non-technical performance, a simple test could help to identify individual training needs and deficiencies in performance, and thereby optimize educational benefit and economize the budgets of surgical residency programs in Ontario.
Dr. K.S. Jhaveri
University Health Network
Comprehensive evaluation of disease status in primary sclerosing cholangitis by MRCP and MR elastography through hepatic fibrosis estimation with comparison to FibroScan
Primary sclerosing cholangitis (PSC) is a chronic liver disease that causes injury and narrowing of bile ducts which can lead to liver cancer and/or liver failure due to fibrosis/cirrhosis. The diagnosis is challenging, usually requiring a multidisciplinary approach with MRI playing a dominant role. Accurate disease status evaluation could help triage optimal treatment including liver transplantation; however there are no reliable tests to track disease progression.
Liver biopsies have multiple drawbacks including sampling issues (from disease heterogeneity), complications, and costs. MR elastography (MRE) which has been shown to estimate liver fibrosis noninvasively and accurately could prove to be a useful tool to assess disease stage in PSC. Estimation of liver fibrosis by MRE along with MRI derived morphological information (MRCP) will be used in this study to provide a non-invasive imaging biomarker for evaluating disease status in PSC.
Successful outcomes can provide better treatment triage including earlier enlistment for liver transplantation via accurate and non-invasive estimation of actual disease status in PSC. MRE and MRCP, through its ability to evaluate disease status in PSC, could also provide an imaging biomarker for future development and efficacy evaluation of novel drug treatment for PSC.
Dr. P.J. Karanicolas
Sunnybrook Health Sciences Centre
Tranexamic acid versus placebo to reduce perioperative blood transfusion in patients undergoing major liver resection: a pilot randomized controlled trial
Surgery (liver resection) is the optimal treatment for patients with liver cancer. Despite improvements in liver resection surgery, 30-40% of patients require blood transfusion during or after their surgery. While blood transfusions are generally safe, patients who receive blood transfusions are more likely to experience complications such as death; furthermore patients who receive blood transfusion have a higher likelihood of cancer recurrence.
This study, which will determine the effect of a drug named “tranexamic acid” (TXA) on blood loss and the need for blood transfusion after liver resection, will involve co-investigators from Toronto, Calgary, Montreal, and Halifax. Over 60% funding for this study has been secured from the Canadian Institutes of Health Research Operating Grant program.
Over 2000 patients undergo liver resection each year in Canada. If the use of TXA significantly reduces the need for transfusion it would be clinically meaningful, especially since it is a cheap ($36 per patient) treatment – much lower than any other blood product that could otherwise be given. Findings from this pilot trial will be used to establish the feasibility of proceeding with a larger trial in Canada.
Dr. J. Khan
Dr. S. Choi
Sunnybrook Health Sciences Centre
Pregabalin and lidocaine in breast surgery to alter neuropathic pain (PLAN): a pilot study
Post-mastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that develops after breast cancer surgery. Surgery is an integral component in the management of breast cancer and it is estimated that up to 65% of those who underwent breast cancer surgery will suffer from PMPS. The pain syndrome is refractory to conventional therapies and can persist for several decades. Administering an infusion of lidocaine during the initial breast cancer surgery has emerged as a possible intervention to prevent the development of PMPS; furthermore patients taking pregabalin during the time of their surgery have been shown to have significantly decreased rates of chronic pain associated with their surgery.
The objective of this study is to determine the whether an infusion of lidocaine during surgery and pregabalin given around the time of surgery can reduce PMPS after breast cancer surgery. This pilot study will also aim to inform the feasibility of a larger, multicenter study. A factorial randomized controlled trial design will be used to assess these two interventions. Patients, healthcare providers, data collectors, and analysts will be blinded to group allocation. Patients will be followed up at 3 and 6 months after surgery to determine the incidence of PMPS.
Dr. R.H. Manocha
Dr. G.J.W. King
Rehabilitation of the ligament-deficient elbow: a biomechanical study
The elbow is the second most commonly dislocated joint. Dislocations can result in injuries to one or both of the elbow’s ligaments. Ligament injuries can also occur with fractures and chronic overuse, as is common in throwing athletes such as baseball pitchers. Following ligamentous elbow injury, motion must be restricted to prevent recurrent instability and to allow for optimal ligament healing; however if immobilized, the elbow is prone to developing stiffness, which can be functionally disabling.
There is little biomechanical evidence guiding the rehabilitation of the unstable elbow. Using cadaveric specimens and a well-established upper limb motion simulator that both generates and measures joint movement, the aim of this study is to compare common rehabilitation protocols used in elbow instability. Three clinical scenarios will be examined: lateral collateral ligament (LCL) injury, medial collateral ligament (MCL) injury, and combined LCL and MCL injury. The effects of forearm rotation, muscle activation, and arm positioning during typical exercises will be studied. A hinged elbow brace, often prescribed for these injuries, will also be evaluated to determine whether these costly devices improve stability.
This study will help guide physicians and therapists in prescribing safe exercises and adequate braces in the rehabilitation of the unstable elbow.
Dr. D. Mertz
Prevention of infections in cardiac surgery (PICS)
Infections of surgical wounds after cardiac surgery are common and potentially life threatening. Administration of intravenous antibiotics prior to surgery is a cornerstone to prevent these infections. Despite its importance, the optimal duration and choice of antibiotic prophylaxis remains controversial as reflected by differing recommendations in guidelines and current practices at Canadian centers. One single-dose of antibiotic prophylaxis is well accepted in a majority of surgical disciplines but not in cardiac surgery. Prolonged duration of antibiotic exposure can result in emergence of resistance, infections with Clostridium difficile, and toxicity.
The eventual full scale study will compare short-term prophylaxis (one pre-op and one dose post-op) versus long-term antibiotic prophylaxis (continuation for 48 hours) as well as monotherapy (cefazolin) versus a combination therapy (cefazolin plus vancomicin). The hypothesis is that the combined regimen is superior and that short-term is as efficacious as long-term prophylaxis in preventing these infections.
The proposed pilot study will assess the feasibility of such a trial by measuring the adherence to the study protocol and the proportion of patients with complete follow-up. Blinded assessment of infections will be tested and the event rate to guide sample size calculation will be estimated for the eventual full scale study.
Dr. S. Riazi
University Health Network
Investigation of metabolomics profiling in patients with malignant hyperthermia
Malignant hyperthermia (MH) is considered a metabolic disorder, but little is known about the exact mechanism of MH-induced hypermetabolic state. One puzzling property is phenotypic variability among MH-susceptible (MHS) patients. Outside of the typical picture of MH reaction, some MHS patients show delayed reaction, some show sensitivity to non-anesthetic triggers such as heat, and exercise; and some MHS patients even develop chronic musculoskeletal symptoms.
In this study, it is hypothesized that elucidating the unknown details behind pathophysiology of MH-induced hypermetabolism can explain the phenotypic variability among MHS patients. The investigators intend to explore the characteristics of MH-induced hypermetabolism by measuring metabolomics (metabolite footprint) in patients’ muscle samples during caffeine-halothane contracture test (CHCT). Specifically, metabolomics will be measured, produced in the process of carbohydrate, and lipid metabolism.
Dr. X. Zhao
Dr. F. Liu
University Health Network
The role of adipose derived stem cells for reversal of radiation fibrosis
Radiotherapy is effective for the treatment of head and neck tumors but has significant side effects. Nearly all patients with radiation treatment to the head and neck develop a fibrosis scar, termed radiation fibrosis, which can significantly impact their quality of life. The process of radiation fibrosis appears months to years after treatment and is often irreversible. The mechanism behind radiation fibrosis involves cell death and dysfunction, lack of blood flow and oxygen to the radiation site, and persistent inflammation.
Recent evidence has shown that fat tissue is host to a population of stem cells which has the ability to improve blood vessel formation and oxygen delivery while decreasing scar formation and inflammation. The study objective is to harness the potential of these fat-derived stem cells to repair fibrosis damage caused by radiation injury. Using a combination of a radiation fibrosis animal model and high throughput gene, protein, and metabolic analysis, the researchers hope to determine the therapeutic effect of transplanting fat-derived stem cells into radiation fibrosis tissue.
Dr. K. Armstrong
Dr. S. McCabe
University of Toronto
Distal radius fracture care in the province of Ontario: factors impacting management
The distal radius bone of the wrist is the most common fracture site in adults. Approximately 8,000 wrist fractures occur annually in Ontario, most commonly in older women. This type of fracture will become more common and the outcome more important as Canada’s aging population desires higher levels of physical function. Wrist fractures can be managed non-surgically with cast immobilization or surgically with cast immobilization and percutaneous pinning, external fixation, or with open reduction and internal fixation (ORIF). These types of surgical management are listed in order from least to most invasive.
At least amongst the population 60 and older with unstable distal radius fractures, systematic review has not shown any clinically significant functional advantage when non-surgical and surgical treatments are compared. ORIF does hasten the recovery period; however this comes at the cost of an increased complication rate.
A trend towards ORIF management of wrist fractures has emerged in multiple other countries including the United States with a potential to impact patient outcomes and healthcare system costs. This study will examine whether similar trends exist over a ten-year period in Ontario. The researchers will determine the temporal, geographical, physician and patient factors that are associated with the treatment of wrist fractures.
Dr. D.A. Dyment
University of Ottawa
Rapid and comprehensive diagnostic sequencing for rare, genetic disease in the critically ill newborn
The goal of this project is to improve healthcare delivery in the Neonatal Intensive Care Unit (NICU) by providing accurate and timely diagnoses to critically ill newborns. The investigators will apply next generation sequencing (NGS) to neonates and sequence the genes associated with genetic disease, known as the “clinome”, and return results to care providers in 1-2 weeks or less.
It is expected the quality and efficiency of a neonate’s work-up to be improved with respect to the number of children attaining a molecular diagnosis, the time to that diagnosis, and the overall cost-effectiveness. Clinome sequencing will also provide an opportunity to perform descriptive studies to assess the experiences of families and physicians with this new technology in the context of the NICU. If successful, there is a potential that clinome sequencing can be part of the front-line genetic investigations in the NICU – similar to the genomic microarray routinely offered to complex patients today.
The outcome of this study may have a significant impact on the how we provide care. For Ontario there is an opportunity to develop a leadership role in the translation of NGS to the NICU as this is not offered on a clinical basis in Canada.
Dr. Y. Finkelstein
Dr. S. Schuh
Hospital for Sick Children
Bronchiolitis epidemiology: air pollution and trends of hospitalization (The BREATH Study)
Bronchiolitis is a common lung disease in infants, which interferes with normal breathing. It is the most common reason for infant hospitalization, and 30-40% of affected babies develop asthma later. There is no medication to cure bronchiolitis; therefore prevention strategies are important.
Air pollution contributes to breathing problems and worsens asthma and other lung diseases but little is known about its influence on bronchiolitis; however we know it affects babies and expectant mothers. An American study found that air-pollution prolongs the hospitalization for bronchiolitis, and that even modest reduction in air pollution would result in significant improvement in the population’s health and save costs. If similar findings were demonstrated in Ontario, these data will inform policy makers, physicians and the public with needed information on the influence of provincial air quality on Ontarians’ health, especially in vulnerable babies.
For the first time in Canada, a group of internationally-renowned experts in medicine, pediatrics, poisonings, epidemiology, health-economics and meteorology will join forces to study the relationship between air pollution and hospitalization of infants for bronchiolitis. Provincial databases hosted at the Institute of Clinical Evaluative Sciences, Toronto, will be linked to study air-pollution risks before and after birth on an individual level.
Dr. L. Jiao
Dr. J. Pernica
Loop-mediated isothermal amplification: a novel molecular method for simultaneous detection of common pathogens in pediatric empyema
Pleural empyema is a suppurative infection of the pleural space which complicates 3-5% of pneumonia in hospitalized children. It is well appreciated that timely antibiotic therapy combined with complete drainage are critical in empyema management; however current conventional culture methods are not only time and labor-consuming, but also bear high false-negative rate.
The overall objective of the present study is to develop a rapid and novel molecular method with high sensitivity and specificity via the multiplex loop-mediated isothermal amplification assay (LAMP) to simultaneously identify common pathogens in pediatric empyema. The target pathogens include Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus anginosus, and Staphylococcus aureus, both methicillin-susceptible and methicillin-resistant.
The investigators’ hypothesize that this molecular test which employs LAMP improves patient care cost effectively by the rapid detection of common pathogens in pediatric empyema with high sensitivity and specificity. This LAMP method offers significant advantages over PCR and conventional microbiology methods for diagnosis in clinical settings. Currently there is no comparable commercial test or any in-house tests published adopting this technology for pediatric empyema.
Dr. V.S. Liang
Dr. A.M. Easson
Princess Margaret Hospital
Patterns of invasive palliative procedures performed in patients with metastatic colorectal cancer
Invasive palliative procedures can play an important role in relieving symptoms and improving quality of life for patients with metastatic colorectal cancer. About 47% of patients with metastatic colorectal cancer undergo at least one procedure for palliation, and 12.5% of all operations performed by cancer surgeons are with palliative intent; however very little is known about the patterns and optimal timing of palliative procedures in this part of the cancer journey.
This study explores the patterns of invasive palliative interventions (IPI) performed on patients with metastatic colorectal cancer over a 10-year period. The IPIs of interest include surgical, endoscopic, interventional radiologic and bedside drainage procedures. This study also investigates whether the pattern of IPIs have changed after the widespread use of new chemotherapy regimens since 2005.
This is a retrospective comparative cohort study of patients with metastatic colorectal cancer treated at Princess Margaret Hospital, identified through the palliative care database. Primary outcomes include the type and frequency of IPI. Secondary outcomes include the timing of IPI and palliative referral with respect to the time of diagnosis of metastatic disease and death. The pattern of IPI and timing of palliative care referral were compared between two time periods: 2000-2004 and 2006-2010.
Dr. J.C. Marshall
St. Michael’s Hospital
Cellular and molecular mechanisms of neutrophil survival in sepsis and trauma: the role of PBEF/Nampt/Visfatin
The Multiple Organ Dysfunction Syndrome (MODS) is the leading cause of mortality in contemporary intensive care units (ICUs). Trauma and infection are its most common causes. The researcher’s laboratory studies the role of the neutrophil - a potent early inflammatory cell – in MODS. The laboratory was the first to show that circulating neutrophils from patients with MODS persisted in an activated state, by subverting a constitutive apoptotic program. A novel protein was identified – PBEF/Nampt/visfatin – as being central to inhibiting neutrophil apoptosis.
PBEF plays a key role as an enzyme that catalyzes the synthesis of NAD from nicotinamide. The investigators have found that NAD alone can inhibit neutrophil apoptosis, and in work funded by the PSI Foundation, that PBEF-mediated generation of NAD requires its interaction with the insulin receptor. The researchers hypothesize that NAD generated by PBEF supports neutrophil survival in critical illness, and seek to further understand how PBEF interacts with the insulin receptor to produce NAD, how NAD regulates neutrophil survival, and how the survival of neutrophils from critically ill patients can be altered by targeting PBEF. Together these studies provide insight into a common and complex disorder, and point to novel strategies to improve outcomes for critically ill Ontarians.
Dr. P. McHardy
Dr. S. Choi
Sunnybrook Health Sciences Centre
Comparison of the effects of perineural versus systemic dexamethasone on low dose interscalene brachial plexus block: a randomized trial
Shoulder surgery is painful regardless of arthroscopic or open surgical technique. Prior to the use of interscalene brachial plexus nerve block (ISB), patients required postoperative admission and treatment with strong intravenous opioids such as morphine. This can have negative side effects including dose dependent respiratory depression, worsened obstructive sleep apnea, sedation, nausea, and vomiting.
ISB provides superior analgesia and reduced opioid consumption. The analgesic and opioid sparing effects of ISB facilitate ambulatory shoulder surgery that it is standard of care. ISB wears off, typically after 12 to 16 hours, unmasking the moderate to severe pain of the surgical insult. Efforts to prolong the analgesic duration of ISB include placement of indwelling catheters or combining perineural medications, most commonly the corticosteroid dexamethasone, with local anesthetic for single injection ISB. The use of indwelling catheters is limited because of technical challenge with placement, or patients being geographically remote from managing centres.
Several studies have demonstrated that perineural dexamethasone significantly prolongs the duration of ISB (~50%). None have compared perineural to systemic dexamethasone (frequently used for the treatment of postoperative nausea). This will be the first study to compare both modes of dexamethasone administration in the context of low dose ISB.
Dr. M. Mouzaki
Hospital for Sick Children
Intestinal microbiota, bile acids and non-alcoholic fatty liver disease: is there a link?
Fatty liver is the most common liver disease affecting children and adults and is associated with obesity. It is not exactly known why fatty liver happens, how or why it progresses. Some people need a liver transplant to recover from severe fatty liver disease.
The investigators’ previous research suggested that gut bacteria may play a role in the development of fatty liver. These bacteria can affect appetite, increase the amount of calories people get from their diets and change the way fat is used by the liver. Bacteria can also change the way bile salts are recycled in the body. Bile salts are produced in the liver. They are important for fat digestion but also play a role in the way the liver processes its fat. Bile salts are also able to influence inflammation. The majority of the bile salts in the body are recycled; however gut bacteria can disrupt this recycling and lead to bile acid losses in the stool. This can potentially lead to increased fat and inflammation in the liver.
The goal of this study is to understand the role that intestinal bacteria and bile acids play in the development and progression of fatty liver disease in children.
Dr. J. Singh
Dr. L. Munshi
University Health Network
Predictors of apnea and their relationship to time to death following withdrawal of life sustaining therapy for donation after cardiac death candidates
Organ donation is a life-saving treatment for hundreds of individuals with terminal diseases. Advances in care have increased the number of people awaiting organ transplants. This growing wait list outstrips the number of available organ donors, and some people die while waiting for a transplant.
Donation after cardiac death (DCD) is a method that has expanded the pool of potential organ donors. The option of DCD is presented to substitute decision makers after the decision is made to withdraw life-sustaining therapy due to medical futility or previously expressed patient wishes/values. In DCD, organ procurement teams wait on standby during withdrawal of life support to see if organs will be able to be procured; however if the dying process is prolonged following withdrawal of life support, organs are not eligible for transplantation and the teams are dismissed. Consequently, predicting time to death is important (1) for accurate communication with families and (2) to ensure that resources are only committed to potential donors with a reasonable probability of successful procurement.
Using data collected by Trillium Gift of Life Network, the objective of this study is to create a novel prediction tool based that will accurately predict time to death after withdrawal of life sustaining therapy.
Dr. P. Szasz
Dr. T. Grantcharov
St. Michael’s Hospital
The development of feasible, reliable and valid in-training milestones as a means to assess technical and non-technical competence in General Surgery trainees
At the completion of surgical residency training, the Royal College of Physicians and Surgeons of Canada (RCPSC) examines residents by a multiple-choice examination and an oral examination and determines whether they are adequately trained in knowledge and judgment to enter the workforce as independent practitioners. Although, knowledge and judgment are also assessed during residency on a yearly basis, technical performance and non-technical performance (i.e. communication, teamwork, professionalism) are never objectively assessed at the completion of training, or more importantly on a yearly basis, where performance deficits can still be remedied.
More recently, there has been a push from various governing bodies to assess these two competencies during training, both of which are imperative to becoming an independent practitioner. The goal of this research is thus to develop valid, reliable and feasible objective performance benchmarks (both technical and non-technical). These benchmarks will then need to be completed at certain time intervals (similar to assessments of knowledge and judgment) in order for residents to progress in their surgical residency training and eventually be eligible for their final RCPSC examinations.
Dr. E. Pope
Hospital for Sick Children
Nadolol versus propranolol for patients with infantile hemangioma: a randomized controlled non-inferiority trial
Infantile hemangioma (IH) is the most common tumor in infants. A treatment is recommended in many cases to control the growth of the tumor and prevent loss of organ function (e.g. loss of vision) or cosmetic deformity. Worldwide, if treatment is deemed necessary, infants are prescribed a blood pressure medication called propranolol. Propranolol reaches the brain, potentially causing short and long-term effects on the developing central nervous system of an infant, particularly memory problems.
medication similar to propranolol, may work the same or better than propranolol and potentially be safer because it cannot reach the brain. This research proposes to study the two medications in a comparison study, by allocating at random, an equal number of patients (40) to receive either propranolol or nadolol and by measuring the tumor shrinkage and potential adverse effects at 24 weeks.
The investigators are hoping to prove that the response to nadolol will be no less than 10% or superior of that to propranolol and because of its properties prove to be a safer alternative for infants requiring treatment.
Dr. M.R. Mitri
Dr. I. Harle
Perceptions of physicians on the adoption of a palliative care approach in patients with COPD
Chronic Obstructive Pulmonary Disease (COPD) is an incurable chronic disease of the lung that is associated with high rates of death. Patients suffering from COPD are not commonly treated with a palliative care approach despite the need for this approach in this patient population. The purpose of this research is to understand the extent to which doctors use a palliative care approach in patients with COPD.
The objective is to answer the following questions: 1) What are the approaches physicians adopt when caring for patients with COPD? 2) What conditions have influenced the adoption of a palliative care approach?
Research design will focus on capturing the mindset of the doctor when faced with a patient with COPD. Following clearance by the General Research Ethics Board, interview questions will be first tested out. Doctors from different specialties will be individually interviewed. After transcribing word for word the taped interviews, participants will be invited to review their responses; thereafter the data will be analyzed and evaluated. Analyzing the data requires finding patterns and common themes in the responses of the participants.
Dr. I. Abdulla
Dr. G. Athwal
Indomethacin prophylaxis for heterotopic ossification after surgical treatment of elbow trauma: a randomized, prospective, double-blinded study
Heterotopic Ossification (HO) is a condition whereby bone deposits form in muscles and soft tissues around a joint. It is a common complication of elbow trauma resulting in pain, loss of elbow motion and function. Surgical treatment of HO is technically demanding, has a high risk of complications and the results are unpredictable. Preventing HO from developing is paramount to the successful treatment of elbow trauma.
Indomethacin, a non-steroidal anti-inflammatory medication is used to prevent HO after hip and pelvis trauma. There is no high level-of-evidence study examining its effectiveness in preventing HO around the elbow and its use is not without any risks. Indomethacin may delay bone healing, cause gastric ulceration, increase the risk of thromboembolic and myocardial events, and bleeding complications.
This randomized, double blind study, will examine whether the use of indomethacin in the prevention of HO will benefit patients suffering from traumatic elbow injuries. 150 patients will be randomized to the treatment or control group. The treatment group will receive indomethacin while the control group will receive a placebo. Post-operative management will be identical for both groups. X-ray assessment and validated questionnaires regarding pain and overall elbow function will be completed at regular post-operative intervals.