Foundation Funded Projects for 2012

 

October 1 to December 31, 2012

July 31 to September 30, 2012

April 1 to June 30, 2012

January 1 to March 31, 2012

 

October 1 to December 31, 2012

In the fourth quarter of 2012, the Foundation approved grants for the following projects:

 

 

Dr. M. Atri
University Health Network

Utility of Shear Wave Elastography in scoring liver fibrosis and prediction of response to treatment in hepatitis C virus (HCV) patients

This study proposes to assess liver parenchymal disease using a new ultrasound technique called Supersonic Shear Imaging (SSI). The aim is to compare SSI elastography with biopsy, the current gold standard, in patients with hepatitis C virus. It is thought there would be a close relationship between higher levels of parenchymal stiffness, as measured by SSI, and severity of liver fibrosis. A pilot study will also run to assess a group of patients pre- and post-treatment who are starting antiviral therapy to correlate treatment response with changes in the elastography values.

About 20 random liver biopsies are performed weekly at Toronto General Hospital. An SSI machine is placed in the biopsy centre and patients who consent will undergo SSI elastography prior to biopsy on the same segment of liver. Elastographic data will then be processed and correlated with biopsy result and laboratory findings. It is expected that one patient per week in the second group will be scanned, who will receive treatment.

If there is good correlation between biopsy finding and stiffness level obtained from SSI, the technique will have the potential of reducing the number of liver biopsies, and will be utilized for ongoing assessment of liver parenchyma. It may also improve the ability to predict response to treatment.

 

 

Dr. D.L. Dance
Dr. B.C. Craven
Toronto Rehabilitation Institute

Exploring the Associations between Daily Blood Pressure Fluctuations and Cardiovascular Risk among Patients with Motor Complete Spinal Cord Injury: A Pilot Study

Patients with spinal cord injury (SCI) experience disproportionately high rates of cardiovascular disease, even when conventional risk factors are considered. Blood pressure control is affected by injuries to the spinal cord and the autonomic nervous system among patients with tetraplegia and upper thoracic paraplegia. These impairments result in vulnerability to frequent short term fluctuations in systolic blood pressure (high and low) during self-care activities such as voiding or defecating.

This pilot study will document the daily fluctuations in blood pressure during a SCI patient’s daily self-care activities using 24 hr mobile blood pressure monitors. In addition, aortic arterial stiffness, a correlate of cardiovascular disease, will be measured via ultrasound. This pilot study will explore the associations between transient increases in blood pressure (how much, how often, and for how long) with arterial stiffness. Future interventions to reduce blood pressure fluctuates over time may reduce the frequency of heart attack and stroke among patients living with chronic SCI.

 

 

Dr. T. Huynh
Dr. R. Aviv
Sunnybrook Health Sciences Centre

Developing a focused-ultrasound animal model of hemorrhagic stroke

Hemorrhagic stroke, characterized by bleeding into the brain, accounts for 10-30% of all strokes. It is the most deadly and disabling type of stroke and only 20% of patients regain functional independence. There have been little improvements in morbidity/mortality over the last 20 years and there remain no proven treatments.

Research achievements have been modest in part by limitations of animal models to accurately reproduce the human condition. Current models rely on blood or bacterial product injection into the brain and do not simulate spontaneous blood vessel rupture. This has precluded study of the dynamic process of acute hemorrhage growth and radiographic dye leakage into the enlarging hemorrhage - both important predictors of early clinical deterioration and poor outcome. New clinically relevant models are needed.

Development of high-intensity focused ultrasound (HIFU) technology has now enabled non-invasive targeted rupture of blood vessels mimicking vessel rupture seen in humans. This project aims to develop a novel hemorrhagic stroke animal model using real-time magnetic resonance imaging-guided HIFU enabling study of hemorrhage formation, growth, and radiographic dye leakage in addition to characterizing the importance of timing and dose of drug interventions.

 

 

Dr. D. Mikulis
Dr. R. Green
University Health Network

Time course, clinical correlates and incidence of neurodegeneration in the first year of moderate-severe Traumatic Brain Injury

Survivors of moderate to severe traumatic brain injury (TBI) endure life-long cognitive, motor and emotional dysfunction, resulting in unemployment, family discord, social isolation and suicide. A barrier for the development of effective treatments to offset these consequences is our limited understanding of the brain’s recovery. In particular, there is a dearth of research into impediments to recovery.

Ongoing degeneration in the chronic phase of TBI has been revealed, which is associated with poorer behavioural functioning. Consequently, researchers have recently begun to describe TBI as a neurodegenerative disease, rather than a discrete injury. Research is critically needed to better understand the characteristics of neurodegeneration in TBI.

In this regard, the objectives of this study are to: (1) characterize the time-course of neurodegeneration within the first year of injury,by measuring brain changes at 3, 6, 9 and 12 months post-injury using neuroimaging, (2) measure how many patients show neurodegeneration; and, (3) measure cognitive impairment and real-world functioning correlates of neurodegeneration. The results will help us to better understand the scale and nature of neurodegeneration in moderate-severe TBI, and to determine when and how to intervene to improve people’s clinical outcomes.

 

 

Dr. N. Paul
University Health Network

Ultralow Dose Computed Tomography for Assessment of Pulmonary Thromboembolic Disease

Pulmonary embolism (PE) is responsible for the deaths of 150,000 US patients every year. It is a condition in which blood clots travel from the veins of the lower body and lodge in the arteries of the chest. One of the most commonly used imaging tests is a CT scan of the lung arteries (CT pulmonary angiogram, CTPA). As an increasing number of CTPA scans are performed in the Emergency Departments (ED), a larger number of patients seen are young women vulnerable to possible harmful long term risks of radiation exposure. This is compounded by the obesity epidemic as an increasing number of patients for CTPA scans are obese and the larger body size requires a larger radiation dose to obtain quality CT images. There has been relatively little research work on individualizing the X-ray exposure to the actual body shape and size of the patient.

A two stage study is proposed in which a range of PE findings are simulated in different sized realistic chest phantoms to determine the best X-ray technique that balances radiation dose and image quality for each body type. These optimized CTPA protocols will then be applied to patients in ED referred to rule-out PE. 

 

 

Dr. F. Quittnat Pelletier
Dr. C.E. Lok
Toronto General Hospital

Validation of a practical diagnostic approach to catheter-related blood stream infections in hemodialysis patients with central venous hemodialysis catheters

Infections are the second most common cause of death in hemodialysis patients, with catheter vascular access as main source of bloodstream infections. In Ontario, over 75% of patients begin hemodialysis with a central venous catheter, putting these patients at risk for catheter-related bloodstream infections (CRBSI). Currently, there are no validated diagnostic criteria for CRBSI in hemodialysis patients. National guidelines recommend diagnosis methods that were obtained from non-dialysis populations and may not be applicable to the dialysis patient because the use of the catheter differs in many ways. For example, while oncologic patients receive medications through their catheter, hemodialysis catheters create circulating blood flow between hemodialysis machine and patient.

This study aims to 1) determine the accuracy of blood results from the dialysis circuit compared with the by the national guidelines suggested “gold standard” peripheral vein blood, 2) assess the feasibility of obtaining blood from peripheral veins during hemodialysis in this patient population which is known to have poor vessels; 3) determine the correlation between bacterial growth in the blood and presenting infectious symptoms.

With this project we hope to validate our current practices to be able to deliver our patients with the safest care possible along with the least discomfort. 

 

 

Dr. A. Sener
Western University

The protective role of supplemental hydrogen sulphide in allogeneic renal transplantation following prolonged cold storage

Kidney failure is on the rise. Although kidney transplantation is the best manner in which to treat kidney failure, only a limited number of donor organs are available. To accommodate this shortage, centers have begun to transplant kidneys from older and less healthy donors. Unfortunately, these organs are more prone to injury that occurs as a result of the decreased blood flow and nutrients the kidneys face when they are removed from the donor. This damage may lead to increased rates of organ rejection, and poor transplant kidney function.

It has been shown in animal models of genetically identical kidney transplantation that the supplementation of standard preservation solutions with hydrogen sulphide during cold storage, a naturally occurring compound in all animals including humans, leads to an impressive improvement in kidney function and recipient survival.

This study proposes to determine whether the protective effect of hydrogen sulphide will be maintained when transplants are performed between genetically different animals, as less than 0.5% of all kidney transplants are done between genetically identical twins. The findings will not only enable future human clinical trials, but will also play a major role in improving existing organ preservation techniques and overall transplant kidney function and survival.

 

 

Dr. N. Srour
Dr. S. Aaron
University of Ottawa

Impact of infection with transmissible strains of Pseudomonas aeruginosa on lung transplantation outcomes in patients with cystic fibrosis

Infection with P. aeruginosa is frequent among cystic fibrosis (CF) patients and is associated with poor outcomes. A significant proportion of Ontario CF patients are infected with transmissible strains of P. aeruginosa. 446 CF patients were previously identified, 320 of which were infected with P. aeruginosa. It was determined that 102 of them were infected with transmissible strains. These transmissible strains are associated with poorer clinical outcomes than unique strains but it is not known if transmissible strains are also associated with poorer outcomes following lung transplantation, one of the treatments for CF.

Ontario patients with cystic fibrosis who have had lung transplantation will be identified and information regarding how well they did after lung transplantation will be collected, particularly how long they lived. The objective is to determine if those patients infected with transmissible strains of P. aeruginosa do worse after lung transplantation than those infected with unique strains of P. aeruginosa.

It is important to determine if those infected with transmissible strains of P. aeruginosa are at increased risk post-transplant because this may impact on the decision to transplant these patients, and these patients may also need to be treated more aggressively following lung transplantation.

 

 

Dr. S. Unger
Hospital for Sick Children

Impact of Feeding Type and Nutrient Fortification on the Gut Microbiome of Very Low Birth Weight Infants

In Canada, the leading cause of infant death and disability is preterm birth. Optimum nutrition is critical in provision of the best care. Mothers’ own milk is the best nutrition as it contains live cells and indigestible sugars that promote colonization of the infant with protective versus pathogenic bacteria.

Beneficial colonization is the first line of protection against overwhelming infection and inflammation, both common and devastating in very low birth weight (VLBW) infants. Most mothers of VLBW infants are unable to express enough milk for their babies and need to supplement with formula or pasteurized human donor milk (PDM). Most gut colonization research has focused on term babies using cultures which miss 80% of all organisms. It is unclear what effects pasteurization of PDM, which kills all live cells, and adding cow's milk-based fortifiers to milk, necessary to meet the high nutrition demands of VLBW infants, may have.

The goal is to characterize bacteria colonizing VLBW infants fed mothers’ milk, PDM or formula using sophisticated molecular techniques on bacterial DNA from stool. These findings will provide a key reference for understanding what represents optimal colonization in VLBW infants and guide nutritional strategies to best promote the health of fragile babies.






July 1 to September 31, 2012

In the third quarter of 2012, the Foundation approved grants for the following projects:

 

 

Dr. R.E. Agarushi
Dr. G.P. Moore
University of Ottawa

A randomized controlled trial: suprapubic aspiration versus urinary catheterization in the neonatal intensive care unit

Urinary tract infection (UTI) is relatively common in infants with an occurrence rate of up to 10%. It is more frequent in male and preterm newborn infants and can lead to significant problems including blood infections, kidney infections, and kidney scarring which can lead to problems with how the kidneys work later in life.

Analysis of collected urine for the presence of bacteria or fungus is the only way to make a certain UTI diagnosis, and urine culture results may take 24 to 48 hours to become available. Sterile collection of urine can be achieved in newborn infants by urinary catheterization (UC) where a catheter is passed through the urethra into the bladder, suprapubic aspiration (SPA) where a needle is inserted into the bladder through the abdominal wall, or ‘clean catch’ where urine is collected into a sterile bottle as the baby urinates during preparation for UC. The main advantage of SPA is that it bypasses the bacteria that normally reside in the urethral opening, thus minimizing the risk of contaminating the sample.

In this study, urine will be collected from infants admitted to the NICU using either SPA or UC and then comparing the contamination rates, success rates and complication rates between these two methods. The infants who undergo SPA will also have an ultrasound (U/S) assessment for the presence of urine in their bladder to help improve the success rate of obtaining urine. Infants who undergo UC will not have an U/S assessment for the presence of urine in their bladder, as our goal is to compare U/S assisted SPA to the usual practice for urine collection in our NICUs which is UC without U/S.

 

 

Dr. A. Alali
Dr. A.B. Nathens
St. Michael’s Hospital

The impact of tracheostomy timing on the outcome of traumatic brain injury

Severe traumatic brain injury (TBI) victims often require tracheostomy (a surgical procedure to create an opening in the windpipe) during their clinical course mainly for airway protection and to help with clearance of respiratory secretions. However, the impact of tracheostomy timing on clinically relevant outcomes of TBI patients remains controversial.

Using a large database derived from the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP), the impact of tracheostomy timing in TBI patients on the following clinically relevant outcomes will be explored: in-hospital mortality, total ventilator days, intensive care unit and hospital length of stay, and incidence of pneumonia, deep venous thrombosis, pulmonary embolism and pressure sores.

In addition, the knowledge, perceptions, and beliefs that might influence timing of tracheostomy in TBI patients will be studied through a survey of neurosurgeons, trauma surgeons and intensivists from trauma centers across Canada and the United States.  

 

 

Dr. M. Bromwich
Dr. K. Baetz
University of Ottawa

Identification and isolation of a yeast ceruminase for management of human earwax

Cerumen impaction (plugged ears due to wax) is the single most common ear related complaint that results in referral to an ENT specialist with an incidence of 3% in the general population. No pharmaceutical exists which is demonstrably better than water for the treatment of this common condition. Discovery of novel effective therapeutics to dissolve earwax would allow treatment without mechanical extraction and a doctor’s visit.

One strategy would be to identify enzyme(s) that specifically breakdown wax, relieving the cerumen impaction. Yeast species are one of the few organisms with the documented ability to digest wax, indicating that their genome must contain an enzyme necessary to breakdown long-fatty acid chains of wax. In this study, yeast enzyme(s) with the ability to digest human earwax will be identified and optimized. This will be accomplished by systematically screening every protein in yeast for their ability to digest wax using high-throughput robotics screening methods. Once enzyme(s) are identified, we will optimize the enzyme(s) activity for digestion of human earwax. Development of a new pharmaceutical for the treatment of cerumen impaction and its associated morbidities is the final goal of this translational research.

 

 

Dr. E. Duan
Dr. J. Centofanti
Dr. D. Cook
McMaster University

ICU Daily Goals Checklist: a mixed methods analysis of effects on communication & patient care

A Daily Goals Checklist (DGC) has been implemented in several intensive care units (ICUs) over the past decade. This tool facilitates communication among clinicians by shared formulation of the care plan for each patient. DGCs help to emphasize a comprehensive, patient-centred multidisciplinary approach to daily rounds. In 2010, based on early published reports and endorsed by interest in our community, a DGC was implemented in the 19-bed tertiary care medical-surgical ICU of St Joseph’s Healthcare in Hamilton, Ontario, Canada.

The objectives of this study are to determine the impact of the DGC on patient care and safety as well as interdisciplinary communication, and to identify potential improvements to the DGC that will enhance its effectiveness clinically and educationally. Data collection methods include semi-structured interviews and focus groups of ICU clinicians, field observations of ICU rounds, and analysis of completed DGCs. Quantitative methods will be used to analyze current use of the DGC. Qualitative methods will be used to analyze data from interviews, focus groups, field observations, and completed DGCs. An active knowledge translation agenda is planned at study completion.

 

 

Dr. L.A. Dubois
Dr. T.L. Forbes
Western University

APPROPRIATE study: Assessing Patient Preferences for and Ranking of Outcomes Presented in Randomized Trials of Endovascular aortic surgery

Endovascular aneurysm repair (EVAR) has emerged as an accepted treatment modality for abdominal aortic aneurysms and is associated with reduced short-term death when compared to open repair. Only a hand-full of differences between the two procedures have been examined in clinical trials and no trial sought patient input when they decided on which differences to examine.

The aim of this study is to compare the relative importance of studied outcomes reported in randomized trials of endovascular aneurysm repair with un-studied outcomes. It is hypothesized that many outcomes not captured in current randomized controlled trials are equally as important to aneurysm patients as studied outcomes. Studied outcomes will be obtained from the literature and un-studied outcomes will be obtained from patients who have had aneurysm surgery. Patients will be asked to rank outcomes studied in trials and compare their relative importance to un-studied outcomes and to ones ranked by surgeons. By highlighting a potential discrepancy between what outcomes are studied, what outcomes are important to patients, and what outcomes are important to surgeons, we hope to identify potential areas for further study and promote patient-driven outcome selection in future trials in vascular surgery.

 

 

Dr. H. Faghfoury
Dr. I. Tein
Mount Sinai Hospital

Identification of carnitine-responsive cardiomyopathy and myopathy in adult patients with dilated and/or hypertrophic cardiomyopathy and limb girdle weakness

There are some adults with skeletal muscle weakness (called “myopathy”) and heart muscle weakness (called “cardiomyopathy”) who have low blood levels of a compound called carnitine as a cause of their problems. Carnitine is very important to energy production in muscles. In fact, there are reports of some people with carnitine deficiency who have developed myopathy and cardiomyopathy that was completely reversed with carnitine treatment. The main objective of this project is to determine the number of patients who have carnitine deficiency as a cause of their myopathy and cardiomyopathy.

Carnitine levels will be measured in 1000 patients with cardiomyopathy and specific features will be described in all the study patients to see if there are any trends that may help to predict which patients with muscle weakness are at risk of developing low carnitine levels. Patients will be treated with low carnitine levels and observed to see if their cardiomyopathy and their muscle weakness improve. Knowing the exact percentage of myopathy and cardiomyopathy patients with carnitine deficiency will allow patients to be screened in a cheap and targeted way to treat the serious complications of this condition, including heart failure and sudden death.

 

 

Dr. M. Hassouna
University Health Network

Estimation of bladder volume from sacral nerve root recordings

Bladder dysfunctions after spinal cord injury (SCI) are highly detrimental to quality of life and are consistently cited as a top priority in surveys of individuals with SCI. Modulating the activity of the sacral nerve using electrical stimulation is a method used clinically to treat a number of lower urinary tract conditions, for example by improving bladder voiding when voluntary control has been lost. This technology could be substantially improved by using feedback information from the body’s own sensory pathways.

Current systems lack information about bladder volume. As a result, voiding must be performed at regular intervals rather than when the bladder is full, which is less efficient and also potentially inconvenient for the user.

The goal of this project is to develop a system that can monitor bladder volume based on the neural activity in the sacral roots. Enabling users to know how full their bladder is would not only improve voiding efficiency, but also allow them to better manage their bladder function and thereby improve their quality of life.

 

 

Dr. M.M. Lalu
Dr. L.L. McIntyre
Dr. D.J. Stewart
University of Ottawa

In vivo assessment of a cellular clinical-grade immunotherapeutic for septic shock (CELLS2)

Severe infection with shock (septic shock) in the intensive care unit (ICU) is a common problem that accounts for approximately 20% of admissions. Despite intensive treatment 30-40% of patients with septic shock die. Septic shock is associated with immensely uncontrolled inflammation that is the result of the body’s reaction to the infectious organism. Recent animal studies of septic shock suggest that adult stem cells reduce inflammation, repair injured organs, and reduce death. Thus, adult stem cells represent an exciting and promising potential therapy for septic shock.

Our group plans to use adult stem cells to treat patients with septic shock in a clinical trial. Prior to giving patients these cells, the clinical trial cell product needs to be tested in an animal model. Testing will help ensure that the cell product is safe and efficacious. This is the primary purpose of this proposal. CELLS2 will test the clinical-grade stem product in a mouse model of septic shock and measure its effect on organ dysfunction, infection and survival. This will be an important and necessary study prior to using these cells in a clinical trial to treat patients with septic shock.

 

 

Dr. J.J. Wang
Dr. C. McCartney
Dr. S. Choi
Sunnybrook Health Sciences Centre

Determining the minimal effective volume (MEAV 95) for interscalene brachial plexus block for surgical anesthesia

Interscalene block (ISB) is a reliable method for shoulder anesthesia and has consistently demonstrated superior pain relief after shoulder surgery. However, patients may experience complications such as blurred vision, hoarseness and difficulty breathing with standard volumes of local anesthetics. Patients with respiratory diseases are precluded from this anesthetic technique because of the potential effects on breathing and the exposure to the risks of general anesthesia and opioid medications.

It has been demonstrated previously that ultrasound-guided ISB can reduce the volume of local anesthetic required for pain control after shoulder surgery. The next step is to determine if the volume of local anesthetic required for anesthesia can also be reduced. If a lower required volume can be demonstrated for anesthesia this may allow patients previously unable to benefit from ISB to have this technique. This in turn would allow vulnerable populations such as patients with obesity and respiratory disease to benefit from ISB and avoid general anesthesia and opioid-based pain relief. In order to do so an up-down methodology will be used to find the minimum volume of the local anesthetic ropivacaine 0.75% required to allow shoulder surgery to take place in 95% of patients.

 

 

Dr. R.E. Waxman
Centre for Addiction and Mental Health

Education’s impact on healthy seniors’ attitudes and health care preferences regarding different stages of Alzheimer’s disease

This pilot study’s goals are to evaluate and compare the impact of brief education about Alzheimer's Disease (or AD) on healthy elderly people’s attitudes and preferences for medical interventions for common, serious health problems that typically occur during different stages of AD. Of particular interest will be subjects' views about less well-known behavioural and psychological symptoms (or BPSD) of AD (e.g., aggression, psychosis, and apathy). Research subjects’ perspectives will be gathered using a series of treatment choice grids, a questionnaire about beliefs, and focus groups.

The rationale for this study is that public knowledge about certain aspects of dementia, in particular BPSD, is lacking. Family members and physicians tend to be unreliable substitute decision makers for incapacitated patients. Decision-guiding advance directives are infrequently written.

Three hypotheses will be tested: (1) education about mild, moderate, and advanced AD will result in significant changes in subjects’ treatment/care preferences in the moderate and advanced stages of AD, (2) education about BPSD will result in significant changes in subjects’ preferences in all three stages of AD, and (3) a majority of research subjects will prefer pharmacological options despite their potential cardiac and neurologic adverse effects to manage BPSD.




April 1 to June 30, 2012

In the second quarter of 2012, the Foundation approved grants for the following projects:

 

 

Dr. L. Braga
McMaster University

ALPHA: Antibiotic prophyLaxis versus Placebo in infants diagnosed with Hydronephrosis Antenatally: a prospective, randomized controlled trial

Hydronephrosis is a condition in which the collecting tubes inside the kidney are stretched or swollen with accumulation of urine. Hydronephrosis can be caused by a narrowing at the point where the ureters (tubes that carry urine from kidney to bladder) join the kidneys. This narrowing may slow the urine flow out of the kidneys into the bladder, and the accumulated urine can predispose these babies to urinary tract infections (UTI).

The purpose of this study is to determine whether the use of preventive antibiotics lowers the risk of UTIs in infants with hydronephrosis versus no treatment. Currently, physician’s preference determines whether an infant is treated with antibiotics or none at all. To answer this clinical question, a blinded, randomized controlled trial (RCT) will be used to determine whether an infant will receive antibiotic treatment or a placebo (no antibiotic). Randomization means the treatment option will be determined by chance and blinded means the doctor, parents and research personnel will not know which treatment option the patient will receive. This will ensure that all results obtained from the study are free of bias and will determine whether preventive antibiotics are indeed necessary in the treatment of infants with hydronephrosis.

 

 

Dr. T. Cil
University Health Network

Visual imagery and mental rehearsal in surgery

Mental rehearsal, or the action of systematically imagining objects and movements, is a training technique that has been studied extensively in sports psychology. It has been validated and successfully applied in professional sports for over three decades, but use of visual imagery and mental rehearsal in surgery has not been explored.

The goal of this study is to better understand the role that these cognitive processes may play in the acquisition and performance of surgical skills and certain types of surgery. In this exploratory study, qualitative methodology is used to examine the use of mental practice in surgical preparation by surgeons. One-on-one semi-structured interviews will be conducted with 24 surgeons representing different levels of experience and subspecialties. Data will be coded and analyzed using a grounded theory approach.

The findings of this study will be valuable in understanding aspects of surgical planning and judgment. Future applications may include incorporation of these practices into traditional learning paradigms in surgical training.

 

 

Dr. E. Cohen
Hospital for Sick Children

Intrapleural DNase and Tissue Plasminogen Activator in pediatric empyema (DTPA trial)

Bacterial pneumonia can be complicated by the development of a pleural effusion and empyema in children. The incidence of pleural empyema in children has increased significantly in the last 10 years. Short term morbidity for this condition is substantial, but unlike in adults, the long term outcome of this condition for children in developed countries is favourable.

Chest drainage with intrapleural fibrinolytic instillation (using tissue plasminogen activator – tPA) has been shown to be an effective therapy for reducing the duration of illness, but prolonged hospitalization is still common. Recent data from adults suggests that combining intrapleural DNase with tPA maximizes effective drainage and improves outcomes; however, there are no published studies on children.

This proposal is a multi-centre randomized controlled trial comparing the time to discharge from hospital after chest drain insertion in previously well children who present with pleural empyema, treated with intrapleural DNase and tissue plasminogen activator (tPA) via chest drain for three doses over 48 hours compared with three doses over 48 hours of tPA alone. Other outcomes related to effectiveness, safety and cost will be assessed as well.

 

 

Dr. N. Daneman
Dr. R. Fowler
Sunnybrook Health Sciences Centre

Optimizing duration of antibiotic therapy for bloodstream infections

Bloodstream infections affect 15% of critically ill patients and triple their risk of death. Antibiotic overuse is also a common and serious problem in critical care, in that 30-50% of antibiotic use is unnecessary or inappropriate, and results in avoidable drug side effects, Clostridium difficile colitis, increased costs, and spiraling antibiotic resistance rates.

The greatest contributor to antibiotic overuse is excessive durations of treatment. Extensive research has demonstrated that shorter duration is as effective as longer duration antibiotic therapy for many infectious diseases, but this question has never been directly studied for bloodstream infections. A review of the literature and survey of Canadian infectious diseases and critical care physicians support the need for a trial comparing shorter (7 days) versus longer (14 days) antibiotic therapy for bloodstream infections. Prior to performing this trial a prospective observational study will: 1) confirm variability in current treatment practices; 2) identify which patients and pathogens are appropriate to include in a future trial; and 3) confirm that benefits of antibiotics are achieved within the first week.

By defining the optimal duration of treatment for bloodstream infections, this research will maximize clinical cure of individual patients, while minimizing adverse consequences of antibiotics.

 

 

Dr. D.H. Delgado
University Health Network

Association of human leukocyte antigen-G polymorphisms and clinical outcomes post transplantation

Transplantation is currently the treatment of choice for patients with end-stage heart, lung, liver or kidney disease failing maximal medical therapy. Early morbidity is predominantly the result of acute rejection. Long-term survival remains limited by chronic graft rejection.

The Human Leukocyte Antigen-G (HLA-G) is a molecule that has been extensively studied in the context of cancer, infections and transplantation. HLA-G has been implicated in the rejection process after transplantation. Patients with high levels of HLA-G in the blood develop considerably less rejection. Unfortunately blood levels may fluctuate over time and are influenced by multiple factors.

Blood levels of HLA-G are determined by the presence of specific genes. The diversity in the HLA-G gene (polymorphism) has recently been investigated in transplantation. The purpose of this project is to evaluate the association between multiple HLA-G polymorphisms and organ rejection in a large cohort of adult patients post heart, lung, liver and kidney transplantation, and to determine the association between donor/recipient HLA-G polymorphisms and rejection.
Identifying efficient tools to stratify patients who are at risk of developing acute or chronic rejection are important in medical advancement, and may help monitor a patient’s response to adjustments in medical therapy.

 

 

Dr. M.G. Fehlings
University Health Network

Enhancing recovery following cervical spinal cord injury by modulating inflammation with IgG

Acute spinal cord injury (SCI) causes devastating impairment and has dire psychological and economic consequences. Currently, there are few effective treatment options to complement surgical and rehabilitation measures undertaken by physicians and health care practitioners.

Inflammation following SCI can increase damage and worsen functional impairment. Promising preliminary data has shown that immunoglobulin G (IgG) improves functional recovery following SCI, however the optimal dose has not been established, the mechanisms of action not sufficiently defined or how late it can be given following injury been explored. The use of IgG as an immunomodulatory therapy for SCI is attractive, as IgG is already approved for the treatment of clinical disorders such as autoimmune neuropathies and Guillain-Barre syndrome. This is expected to significantly reduce the cost and time associated with clinical translation for application to SCI. Importantly, the clinical translation for SCI is critically dependent on a better understanding of the mechanisms of action.

Given this background, it is hypothesized that IgG will reduce inflammation, promote sparing of neural tissue and enhance recovery of locomotor function after SCI when given in a delayed fashion post-injury. The use of IgG could represent a substantial breakthrough in the current treatment for SCI and will lead to clinical trials of this novel strategy.

 

 

Dr. G. Hovhannisyan
Dr. J. Emili
McMaster University

Syndromic management of gonorrhea and chlamydia in patients with vaginal discharge at the Public Health Sexual Health Clinics in Hamilton, ON

World Health Organization and the Canadian Guidelines on STIs recommend empiric treatment of gonorrhea and chlamydia in patients presenting with vaginal discharge if they are at high-risk for STIs. However, the syndromic approach has never been evaluated in a Canadian setting. While the conformity of physicians to the guidelines is not known, at least a few public health units, including
Hamilton Public Health, practice syndromic management, because most clients attending STI clinics are from high-risk groups and may not return for a follow-up visit.

A retrospective chart review will be conducted between 2009-2011 to study the risk factors for gonorrhea and chlamydia; to determine the proportion of cases who are lost to follow-up; and to evaluate the performance of the syndromic approach in terms of sensitivity, specificity and overtreatment rate in public health STI clinics in Hamilton, ON.

Demographic and behavioral risk factors, clinical and laboratory data will be collected to identify important predictors for gonorrhea and chlamydia, and to evaluate the performance of the syndromic approach. The study database will be linked to Integrated Public Health Information System to define the proportion of cases of gonorrhea and chlamydia lost to follow-up.

 

 

Dr. K.J. Jerzak
Dr. K. Zbuk
McMaster University

Serum and urine markers of metabolic dysfunction in colorectal cancer: a pilot study

The key to conquering cancer is finding aspects of cancer cells that make them unique compared to normal cells. Most of the focus so far has been on structural parts of cancer cells, including proteins, fats and DNA. Recent research shows great potential for targeting the metabolism (the process of energy production) of cancer cells in the treatment and prognosis of cancer patients.

Most cells in our body use oxidative phosphorylation to make energy, but cancer cells favour glycolysis. The goal of this study is to measure small molecule “markers” of glycolysis in the blood and urine of patients with early and late stage colorectal cancer (CRC). Two blood tests (anion gap and osmolar gap) and one urine test (24 hour urine citrate) will be measured as “biomarkers” of glycolysis.
For this pilot study, levels of all three laboratory tests in patients with early stage and late stage CRC will be compared to each other and to normal values.

If there is a significant difference in patients with early stage and late stage disease, these tests may ultimately help diagnose metastatic (widespread) cancer early, prior to detection on CT scans and X rays. Future, larger studies would be planned to determine whether these markers also have the potential to predict patient survival and response to chemotherapy.

 

 

Dr. D. Johnson
Dr. S. Sharma
Queen’s University

Systemic absorption of bevacizumab and ranibizumab in humans treated for choroidal neovascularization secondary to age-related macular degeneration

Age-related macular degeneration (AMD) is the most common cause of blindness in developed countries and affects an estimated 8 million people worldwide. The “wet” or neovascular form of AMD is characterized by the abnormal growth of blood vessels underneath the retina which can leak and hemorrhage to cause severe vision loss. Of several available interventions for this form of AMD, intraocular injections of the vascular endothelial growth factor (VEGF) inhibitors bevacizumab (Avastin) or ranibizumab (Lucentis) are the standard of care for the treatment of wet AMD.

Despite their relative success in stabilizing or improving vision loss, a recently published randomized clinical trial comparing the efficacy of the two agents highlighted a trend for an increased rate of severe systemic adverse effects in patients who had been randomized to bevacizumab injections. While it is hypothesized that these trends are the result of greater systemic absorption of bevacizumab compared to ranibizumab in patients receiving antiVEGF therapy by intraocular injection to treat AMD, no study to date has unequivocally demonstrated this. Therefore, the purpose of the proposed study is to measure and compare the amount of antiVEGF absorption into the bloodstream that occurs following intraocular injections of VEGF inhibitors in patients with wet AMD.

 

 

Dr. S. Lin
Dr. L.J. Morrison
St. Michael’s Hospital

Therapeutic hypothermia: the impact of processes of care on outcomes after cardiac arrest

Cardiac arrest is a common and deadly medical emergency. Up to 45,000 cardiac arrests occur each year in Canada and less than 5% of victims survive. Many patients who do not die immediately develop a complex disease called post-cardiac arrest syndrome, which often proves fatal. Until recently, treatment options have been limited.

Two studies have shown that cooling the body after cardiac arrest improves survival rates and brain function. However, there are many questions about how to best cool patients that remain unanswered, particularly when, where, how and how long to cool patients. The objective of this proposal is to answer the questions about how best to cool the body, and how this can affect patient survival and brain function.

Using data from a large network of 37 hospitals throughout eight southern Ontario regions, statistical models will be constructed that will use improved survival and brain function to answer when, where, how and how long to cool the body of patients after cardiac arrest. The answers to these questions may potentially improve the quality of care provided in all hospitals and increase the number of patients that survive with improved brain function after cardiac arrest.

 

 

Dr. C. McCartney
Dr. S. Choi
Sunnybrook Health Sciences Centre

OPRA (Optimizing Pain and Rehabilitation after knee Arthroplasty)

Knee replacement (TKA) is a common surgical treatment (30,000 p.a. in Canada) that can reduce pain and improve function. Severe acute and chronic pain is a significant problem after TKA with >30% suffering pain one year after surgery. Acute pain is associated with development of chronic pain. 

The best method for pain control after TKA appears to be continuous femoral nerve block (FNB) where a small catheter is placed and local anesthetic infused after surgery causing numbness to the surgical site. A single injection technique also exists and may provide similar benefits. Both techniques require training and are associated with side effects such as weakness that can inhibit rehabilitation.

A newer technique with injections of local anesthetic into the joint after surgery (Local Infiltration Analgesia (LIA)) is becoming common and does not cause weakness and can be done quickly at the end of surgery. Preliminary studies demonstrate that pain control after LIA may not be as effective as the FNB techniques.  Currently we do not know if the femoral nerve block, continuous femoral nerve block or LIA technique is superior for pain relief and a high quality study is required to compare these methods after TKA.  The aim of this multi-centre randomized clinical trial is to determine the optimal perioperative pain relief method to optimize pain control and rehabilitation after total knee arthroplasty (TKA).

 

 

Dr. V.A. McCredie
Dr. A.J. Baker
St. Michael’s Hospital

Observational study of cerebral tissue oxygen saturation during blood transfusion in severe traumatic brain injured patients

Severe traumatic brain injury (sTBI) continues to be a major problem in Ontario, in the developed world and now increasingly in developing countries. The consequences of sTBI include the largest number of life years lost from any cause and one the highest causes of disability. Victims are usually previously active and productive while survivors require extensive rehabilitation. Distinct in sTBI is the observation that brain injury continues for hours to days after the initial trauma. The understanding and prevention of this so-called secondary injury represents the major focus of their critical care as well as the potential source of the observed wide variation in outcome for similarly injured patients.

This secondary injury is thought to be closely linked to insufficient oxygen and blood supply to the brain arising from a number of physiological changes. As well, many of these patients are relatively anemic from the traumatic episode and it seems physiologically rational to transfuse packed red blood cells (pRBCs). However, there are several lines of evidence that suggest that transfusion of pRBCs can be harmful in many forms of critical illness and should only be undertaken at more severe levels of anemia. Thus there is a diverse opinion on the benefits of transfusion in sTBI and an urgent need to understand the neurophysiologic effects.

This proposal aims to provide some objective, non-invasively achieved, physiologically relevant data in order to provide some rational basis for decision-making for transfusion in sTBI. Specifically this proposal is an observational study of transfusion and brain tissue saturation in sTBI patients. The results will illustrate to what degree brain tissue oxygenation is critically dependent on the degree of anemia in sTBI and help in the decision of whether transfusion might be helpful.

 

 

Dr. N.I. Perlis
Dr. M. Krahn
University Health Network

Quality of life and utility elicitation in bladder cancer patients

 “Utility” is a global measure of health status that reflects respondents’ overall preference for various health states. Utilities are used in clinical studies to measure health outcomes, and in population surveys to measure population health. Utility is most frequently used in decision and economic models in order to capture quality-of life (QOL). However, the utilities of bladder cancer states are unknown because they have never been measured.

This study proposes to administer psychometric QOL instruments and elicit bladder cancer utilities using several methods from 250 patients with bladder cancer of varying severity and duration. By analyzing these patient centred, comprehensive QOL data we will have a better idea of the quality of life that faces bladder cancer patients. Our objective is to explore patients’ experiences throughout the entire continuum of bladder cancer diagnosis and management.

 

 

Dr. N. Singh
Dr. A.R. Moody
Sunnybrook Health Sciences Centre

The ability of routine clinical high resolution 3-Tesla MR imaging of carotid intraplaque hemorrhage to identify vulnerable cardiovascular and cerebrovascular patients

Stroke and heart attack vascular events are the leading causes of death in Ontario. The early identification and treatment of patients who will go on to have these events saves lives and improves quality of life. Clinicians currently rely on the degree of narrowing of carotid and coronary arteries due to atherosclerotic plaque to identify patients who might go on to have an event. However, this measure is limited since some patients with low grade narrowing have events, while other patients with high grade narrowing may never have events.

Instability of artery plaque, rather than artery narrowing, is increasingly thought to better identify patients at risk of events. MRI advances allow for visualization of plaque features of instability such as the presence of bleeding or intraplaque hemorrhage. This study primarily aims to assess the relationship of MRI detected intraplaque hemorrhage and vascular outcomes (i.e., cardiovascular and cerebrovascular events). It is hypothesized that MRI detected intraplaque hemorrhage is associated vascular outcomes. This relationship will be investigated using a large (~ 1000 patient) data-set acquired over four years as part of routine care practice to also demonstrate the clinical utility of high resolution MRI.

 

 

Dr. T. Wang
Dr. A. Grin
St. Michael’s Hospital

Correlation of HER2 status in biopsy and resection specimens of gastric and gastroesophageal junction adenocarcinoma

A portion of stomach and gastroesophageal (GEJ) cancers over-produce a protein known as HER2 which is involved in cancer progression. A synthetic drug known as trastuzumab (Herceptin) has been shown to improve survival in patients with stomach and GEJ cancers that over-produce HER2. Ontario currently funds treatment with trastuzumab in patients with advanced stomach cancer that over-produce HER2, however, the tests for HER2 are sometimes only performed on small biopsy specimens, and may not be representative of the whole cancer. Thus, false positive and negative results may be possible, and patients who may benefit from trastuzumab may be denied.

100 cases of stomach and GEJ cancer have been identified where both a biopsy and fully surgically removed cancer specimen are available. This study proposes to test both specimens for HER2 expression to explore how common these inaccuracies can occur, and try to identify risk factors for inaccurate results.






January 1 to March 31, 2012

In the first quarter of 2012, the Foundation approved a total of $869,000 in new grants, for the following projects:

 

 

Dr. K. Boutis
Hospital for Sick Children

Salter-Harris I fracture of the distal fibula: clinical suspicion versus reality

For almost 50 years, doctors have believed that growing children with twisting ankle injuries and normal x-rays do not have ankle sprains. Instead, they thought these children get a fracture of the growth centre in the fibular (calf) bone. However, preliminary research shows that almost all of these children believed to have a fracture actually do have sprains.

It is important to be sure if a child has a fracture or a sprain because the treatment for each of these is completely different. Children with sprains are encouraged to use their ankle as soon as possible, while those with fractures are put in a cast for 4 weeks. Moreover, treating ankle sprains like fractures needlessly costs the Canadian health care system at least 3 million dollars every year.

In this study, children from 2 emergency departments (ED) believed to have an ankle fibular growth centre fracture will get an MRI to determine the percentage with a fracture versus a sprain. The main goal is to prove that the overwhelming majority of these children will have sprains, not fractures. If correct, thousands of children will be spared unnecessary cast treatment and money will be saved in the health care system.

 

 

Dr. N. Dehghan
Dr. R. Jenkinson
Sunnybrook Health Sciences Centre

Early weightbearing and mobilization versus non-weightbearing and immobilization after ORIF of unstable ankle fractures: a randomized controlled trial

Indications for surgical intervention in patients with acute ankle fractures are relatively clear. However, the post-operative rehabilitation protocol with respect to weight bearing and range of motion (ROM) remains controversial. Conventionally the post-operative protocol after open reduction internal fixation (ORIF) includes non-weight bearing and cast immobilization for six weeks. However, a more contemporary approach uses functional bracing and early weight bearing, which is thought to expedite rehabilitation and return to function. The goal of this study is to compare these postoperative protocols in a prospective randomized controlled clinical trial.

The primary research question is whether post-operative treatment with early protected weight bearing improves prognosis for early return to work and improved functional outcome, compared to traditional post-op ankle immobilization in a non-weight bearing cast. Secondary research questions include the rate of adverse events (wound healing, infection, hardware failure) with early weight bearing and ROM comparable to rates with traditional post-op ankle immobilization.

The null hypothesis is that there is no difference in terms of return to work, functional outcome, or adverse events when patients are treated with either post-operative regimen. However, we hypothesize that the early weight bearing group will have earlier return to function and a similar low rate of adverse events.

 

 

Dr. P. Deshpande
Dr. V. Shah
Mount Sinai Hospital

Effect of maternal skin-to-skin contact (SSC) in the delivery room on the skin colonization of preterm infants: a pilot randomized controlled study

Preterm babies are at increased risk of infection during their hospital stay. Soon after birth they get colonized with bugs that are present in the environment [human contact (personnel working in the hospital), incubators etc]. Provision of maternal skin-to-skin contact (SSC) in the delivery room may lead to exposure to bugs that are present on the mother (community acquired) which may be less harmful and lead to less infection.

This study proposes to assess the effect of maternal SSC in the delivery room on the type of organisms that are then present in preterm infants on day 7 of life. After birth, infants will receive maternal SSC or no contact for at least 30 minutes in the delivery room. On day 7 of life, skin swabs will be obtained from the armpit, groin and navel in both groups, pooled and analyzed for bacteria. Further, swabs from the mouth and rectum will be taken and analyzed separately. Prior to SSC or no SCC, nasal and rectal swabs will be obtained from the mother and analyzed for bacteria.

 

 

Dr. M. Ghert
Dr. M. Bhandari
McMaster University

Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY): a pilot randomized multi-center clinical trial

The most effective antibiotic regimen in preventing postoperative deep infections following limb reconstruction for tumor surgery remains controversial and the current state of practice varies widely, particularly with respect to duration of antibiotics.

A two-arm randomized controlled multicenter pilot trial is proposed in which patients will be randomized to receive either 24 hours or 5 days of postoperative antibiotics. The primary endpoint will be deep infection within one year of surgery. The goal of this pilot is to determine the feasibility with respect to recruitment, data quality management, follow up and compliance of a larger definitive trial. The ultimate goal for this trial would be to develop clinical guidelines for post-operative management of Orthopaedic Oncology patients.

 

 

Dr. T.K.Y. Ip
Dr. S. Mehta
Mount Sinai Hospital

A phase 1 study: the determination of the maximum tolerable dosage of nebulized sodium nitroprusside in adult acute lung injury

Acute lung injury (ALI) is a syndrome characterized by acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension. ALI is responsible for significant mortality and morbidity in the critically ill population. Novel rescue therapies used to support oxygenation in severe ALI include inhaled nitric oxide and high frequency oscillatory ventilation; however, neither have been shown to reduce mortality and both are limited by logistical and financial challenges.

Inhaled sodium nitroprusside (iSNP) is a vasodilator which causes local vasodilation of pulmonary capillaries surrounding functional alveoli, resulting in improved oxygenation by redistributing pulmonary blood flow to areas with better ventilation-perfusion ratios. As iSNP can be administered by a low-cost nebulizer and is relatively inexpensive compared to other novel rescue therapies, this modality may be an alternative therapy for patients with severe hypoxemia. Two pediatric studies support the use of iSNP in ALI; however, iSNP has not been studied in the adult ALI population. To determine whether iSNP can improve oxygenation in adult ALI, the maximum tolerable dose (MTD) must first be determined.

This study aims to determine the MTD of iSNP in adult ALI through an open-label, nonrandomized, single centered, dose escalation study design, whereby subjects will receive iSNP for thirty minutes and have various physiologic variables recorded.

 

 

Dr. K.K. Koo
Dr. M.O. Meade
Western University

One-day point prevalence of acute rehabilitation in Ontario intensive care units: rates of, barriers to and facilitating factors for mobilization

Bed rest and sedation during life support are common practice in intensive care units (ICUs). As a consequence, the muscle wasting that occurs can lead to significant long-term disability. Studies show that 46% of ICU patients develop neuromuscular complications and 28% of these survivors sustain debilitating muscle weakness.

Research conducted in medical ICUs suggest that early mobilization in ICU patients is safe, cost effective and can improve outcomes. Recently, a national survey among physiotherapists and physicians illustrated multiple perceived institutional, provider and patient level barriers to mobilization in Canada
ICUs.

The objectives for this study are to determine: 1) actual rates of immobility in patients who should be mobilized but are otherwise not, 2) facilitating factors for mobilization, 3) barriers to immobilization, 4) current mobilization practices, 5) who the participants of acute rehabilitation are & their roles. This work will identify gaps between the perceived and actual barriers to, and facilitating factors of mobilization in critically ill patients. The results of this study will build a foundation to guide future educational and research initiatives to promote ICU rehabilitation in Ontario.

 

 

Dr. J.C. Marshall
St. Michael’s Hospital

Cellular and molecular mechanisms of prolonged neutrophil-mediated inflammation in trauma and sepsis: the role of PBEF/Nampt/Visfatin

Patients suffering from serious traumatic injury or infection are at risk of developing the Multiple Organ Dysfunction Syndrome (MODS) - the leading cause of death in the intensive care unit (ICU).

Neutrophils – white blood cells of the body’s defenses against infection – play a central role in causing the tissue injury of MODS. We were the first to show that neutrophils from critically ill patients remain active, because their normal tendency to die through a suicide program known as apoptosis is impaired.
We hypothesize that prolonged neutrophil survival contributes to organ injury. We have shown that a protein called Pre-B Cell Colony Enhancing Factor (PBEF) is increased in critically ill patients, and prevents normal neutrophil apoptosis.

Building on preliminary studies of PBEF function, neutrophils from critically ill patients who have sustained trauma or serious infection will be used to determine whether the survival activity of PBEF results from its ability to stimulate synthesis of an intracellular molecule called NAD, whether PBEF interacts with the cell receptor for insulin, and whether PBEF biologic function is altered by insulin. Together these studies will point to potentially effective new strategies to reduce organ failure and so to improve outcomes for critically ill Canadians.

 

 

Dr. K. Menon
University of Ottawa

Steroid use in pediatric fluid and/or vasoactive infusion dependent shock (The STRiPES Study)

Approximately 20,000 children per year in North America present to emergency departments, pediatric wards and intensive care units with shock. The treatment of these patients with steroids has a strong scientific rationale; however, the available studies on this subject (primarily in adult populations) have drawn conflicting conclusions. These studies have assessed different patient populations, steroid doses and durations and have provided limited information on the side effects associated with steroid use. Given this variability, it has been difficult to develop consistent guidelines for all critically ill children with shock. The management of these patients remains highly variable with many critical care physicians having strongly held beliefs both for and against the use of steroids in this population.

A multi-centre chart review is proposed to describe 1) the characteristics of patients for whom steroids are currently prescribed; 2) the dose and duration of steroids prescribed; and 3) the association of steroid use with important clinical outcomes in children with fluid and/or vasoactive infusion dependent shock. This information will allow us to establish the current standard of care for steroid use in the management of these patients and provide the background for a well-designed study that ultimately impacts clinical practice.

 

 

Dr. N. Selzner
Dr. G. Levy
University Health Network

The role of the novel FGL2-FcγRIIB inhibitory pathway in human viral hepatitis

Viral hepatitis is a serious world health problem affecting over 1 billion people worldwide. Presently the lack of highly effective treatments results in many patients requiring liver transplantation or death. Our laboratory has defined the role of a unique molecule FGL2 and its receptor fc-gammaR and its role in the pathogenesis of both experimental and human hepatitis.

The studies proposed in the present proposal will test the hypothesis that measuring levels of fgl2 in plasma will identify individuals that will go on to develop chronic disease and inhibition of binding of fgl2 to its receptor will allow the host with both acute and chronic disease to develop an appropriate immune response and clear the virus. The studies will provide rationale for generation of new therapies to improve the treatment of patients with acute and chronic viral hepatitis by targeting fgl2.

 

 

Dr. J. Trier
Dr. N. Dudek
University of Ottawa

Defining success and satisfaction with functional abilities after upper limb amputation

There are currently no clear definitions in the literature of functional success or satisfaction for people with an arm amputation. In the past, the literature has equated success with using a prosthesis, but there is no clear evidence that prosthesis use in arm amputees increases satisfaction with functional abilities.

The purpose of this study is to determine how people with an arm amputation define success and satisfaction with their functional abilities. A qualitative research methodology using modified grounded theory will be employed.
Participants will be recruited from The Ottawa Hospital Rehabilitation Centre’s outpatient amputee clinic. Eligible patients will be invited to participate in a semi-structured interview. Interviews will be recorded and transcribed. Three individuals will identify key issues and themes.

Given that achieving functional success is the cornerstone of rehabilitation programs, it is paramount to better understand how individuals with an arm amputation define success and satisfaction with their function. A qualitative research approach will enrich our understanding of the factors that patients feel contribute to success. This knowledge could prove to be invaluable when developing and evaluating upper extremity amputee rehabilitation programs, as well as counseling patients about prosthetic options and community re-integration.

 

 

Dr. B. Yanagawa
Dr. S. Verma
St. Michael’s Hospital

Elucidating the role of Birt-Hogg-Dube (BHD) in adverse cardiac remodeling

A characteristic of hearts that exhibit elevated size/volume is an increase in the thickness of the heart muscle walls. This is an initial adaptive strategy to normalize wall stress and maintain heart function. Increases in heart size/volume can result in heart failure, heart disease, stroke, and sudden cardiac death.

The evolutionary conserved mammalian target of rapamycin (mTor) protein is a critical regulator of how heart cells grow, multiply, survive and function in response to the increase in heart size/volume. However, how mTor itself, and therefore the activities it subsequently controls, is regulated remains poorly defined.

Birt-Hogg-Dube (BHD) is a tumor suppressor gene and mutations for BHD are linked to the BHD syndrome, a condition which predisposes to higher risks of developing some forms of skin and kidney cancers. The role of BHD in the heart is unknown. Considering that a primary role of BHD is to inhibit mTor activities, our primary hypothesis is that BHD is a novel and yet unrecognized negative regulator of mTor activity and may therefore play an important role in the protective response to pressure-driven increases in heart volume/size. We propose that BHD functions to limit adaptive remodeling, to induce heart cell death and to further heart failure via an mTor-dependent signaling pathway.