The Physicians’ Services Incorporated Foundation This site is primarily for individuals with an interest in the research programs of the Foundation

Report on Granting Activities

April 1 to July 1, 2010

The Foundation approved grants with a total value of $1,572,200 in the second quarter of 2010, for the following projects:

Dr. B. Alolabi
Dr. G.J.W. King
University of Western Ontario

Coronoid fracture repair and reconstruction of the elbow

The direct and indirect costs of musculoskeletal conditions in the U.S. were estimated to be around 849 billion dollars in 2004. The loss of productivity associated with these injuries accounted for 40% of the cost. Although upper limb disorders only comprise 11% of these impairments, they frequently restrict activities for longer periods than disorders of the back and lower extremities; therefore, their costs tend to be higher. Disorders of the elbow, which result in stiffness or instability, are a significant cause of patient disability. Despite advances in understanding the biomechanics of the elbow, and in the diagnosis and treatment of its disorders, there are many questions that have yet to be resolved and their management remains unsatisfactory.

This project will examine the effects of surgical repair of coronoid anteromedial facet fractures and of prosthetic coronoid replacement for type-II transverse coronoid fractures on elbow kinematics and stability.

Dr. D.J. Bagli
Dr. A. Lorenzo
Hospital for Sick Children

Uropathogenic E.coli (UPEC) infection-induced alterations of the uroepithelial cell epigenome as a marker for urinary tract infection risk

Many patients have medical or anatomical conditions for which urinary tract infection (UTI) poses significant health risk. Since it is unknown which such patients will actually develop UTIs, current standard of care involves prolonged treatment with antibiotics or pre-emptive surgery for the underlying abnormality. Since no biological marker exists that can predict which patients are prone to recurrent UTI, many patients are likely being unnecessarily overtreated by antibiotic prophylaxis or surgery.

DNA methylation results in permanent down regulation of gene expression. Pathogen induced methylation and down regulation of genes that are involved in regulation of cell proliferation, DNA repair and immune surveillance is being tested as a cancer marker. The investigators infected human uroepithelial cells with uropathogenic vs. non-pathogenic bacteria and discovered hyper-methylation and decreased expression of a gene, CDKN2A(p16), that regulates cell proliferation in cells infected with uropathogenic bacteria. They will now test whether methylation of CDKN2A is increased in patients with a history of recurrent UTI vs. healthy individuals, and whether CDKN2A methylation can be used as a biomarker to predict which patients may be biologically prone to UTI recurrence. Such a marker could allow customized antibiotic/surgical treatment to those who really need it, and save the health system substantial costs.

Dr. L. Calder
University of Ottawa

Improving the safety of patients who present to the emergency department with respiratory distress: An analysis of adverse events

In emergency medicine, the decision of who to admit versus discharge can be a difficult one. Patients who are short of breath often come to emergency seeking treatment. This study will look specifically at patients diagnosed with pneumonia, flare-up of chronic lung disease (COPD) and water on the lungs (congestive heart failure). The investigators are seeking to find out why these patients return to emergency after being sent home, and if this is due to a problem with how they were diagnosed. These cases will be broken down in terms of how the diagnosis was made, and preventable problems will be identified. In doing so, ways of preventing errors in diagnosis will be proposed, which will enhance patient safety for short of breath emergency patients.

Dr. A.F. El-Khuffash
Dr. P. McNamara
Hospital for Sick Children

The use of echocardiographic and biochemical markers to predict low cardiac output following patent ductus arteriosus ligation in preterm infants

The Ductus Arteriosus (DA) is a wide muscular blood vessel joining the pulmonary artery (main artery to the lungs) to the aorta (main artery to the body) and allows blood to be diverted from the lungs into the aorta during fetal development, since the baby does not breathe until after delivery. The DA normally closes after birth, but if it remains patent (PDA: patent ductus arteriosus), blood continues to flow from the aorta to the pulmonary artery with decreased oxygenated blood to the body. Preterm infants may have many complications, resulting in long term lung and brain injury or death, which have been associated with a PDA. Surgical closure of the PDA is an option if medical treatment fails. Some preterm infants, however, may deteriorate medically following this surgical procedure, due to poor heart function.

There is evidence that starting treatment early, before the deterioration becomes clinically detectable, may improve short term outcomes in these babies. In this study, the investigators aim to test the role of measuring cardiac troponin t (cTnT), and N-terminal pro-B-type natriuretic peptide (NTpBNP) before surgery in predicting the development of poor heart function after surgery. This will potentially allow for treatment to start immediately post-surgery for those who need it.

Dr. A.K. Ellis
Queen’s University

Predicting allergic risk at birth through cord blood analysis

Allergic diseases have reached epidemic proportions in Canada; almost 40% of Canadians are now affected by at least one allergic condition. To slow this ‘epidemic,’ we must better understand what predisposes children to allergies. It is known that having a mother with allergy places a child at higher risk, but the reasons remain unclear.

In this study, the investigators will look for differences in the immune systems of babies at high risk for allergy compared to those that are low risk, and track these children to see if they develop allergy. The goal is to find biomarkers in umbilical cord blood that will help predict who is at risk for developing allergies in the future. In this way, high risk children will be identified for early intervention and preventative strategies to reduce the burden of allergic disease, both in the affected children and in the Canadian population as a whole.

Dr. M.G. Fehlings
M.S. Shoichet, Ph.D.
Toronto Western Hospital

A bioengineered approach to enhance recovery following severe traumatic spinal cord injury

Spinal cord injury (SCI) causes devastating impairment. In up to 30% of cases, the condition deteriorates weeks to years following injury, due to post traumatic syringomyelia (PTS), where scarring around the cord leads to cystic degeneration and neurological compromise. Current surgical treatment for PTS is unsatisfactory, as the scarring leads to persistence of the fluid-filled cysts.

In studies previously supported by P.S.I., the investigators examined the use of HAMC, a bioengineered polymer, as a means to deliver anti-apoptotic compounds to reduce post-traumatic cell death after SCI. During the course of this work, it was discovered that HAMC itself has anti-inflammatory properties, and promising preliminary data indicate that HAMC reduces inflammation, scar formation, and appears to improve neurobehavioural recovery in animals with severe SCI and PTS. Given this background, the investigators anticipate that the use of HAMC could represent a substantial breakthrough in the current treatment of SCI and PTS, and will lead to clinical trials of this novel strategy.

Dr. R.S. Goldstein
West Park Healthcare Centre

Does breathing helium-hyperoxia increase the tolerance of one-legged exercise in ventilatory limited patients with chronic obstructive pulmonary disease?

COPD is a lung disease. Regular exercise can help patients with COPD. Exercise training is the most important part of a respiratory rehabilitation program; therefore, patients with COPD go to respiratory rehabilitation. However, COPD patients have a hard time with exercise training. Their lung disease limits their ability to breathe. One way to improve their exercise program is to train with one leg at a time; another way is to make their exercise easier by breathing a mixture of helium and extra oxygen. It is not known whether putting the two methods, one-legged and helium, together will improve their exercise program even more.

This study will assess whether breathing helium during one-legged exercise improves exercise endurance. If it does, there may be a reason for combining one-legged exercise with breathing helium as part of a respiratory rehabilitation program.

Dr. J. Hall
Dr. M. McKee
St. Michael’s Hospital

A multicentre, randomized trial of conservative treatment versus operative plate fixation for acute, displaced fractures of the distal clavicle

At the present time, the optimal treatment method for acute, displaced fractures of the distal clavicle remains unclear. There are not Level 1 studies of randomized trials to guide treatment, and surgical intervention is based on expert opinion and retrospective reviews. There is an urgent need for a properly powered, randomized, controlled trial to evaluate the differences in patient outcome following either non-operative or operative treatment for displaced Type II distal clavicle fractures.

This study will define predictive factors for non-operative and operative care of individuals with acute, displaced Type II distal clavicle fractures, and will provide the practicing orthopaedic trauma surgeon with Level 1 evidence upon which to base treatment decisions.

Dr. S. Haykal
Dr. T.K. Waddell
Toronto General Hospital

Defining the structural integrity of decellularized tracheal allografts

Cancer, trauma and narrowing following surgical resection of the airway is a major problem in head and neck and thoracic surgery. These patients often require permanent artificial airways to allow them to breathe and speak. Recently, the concept of transplanting an airway from a donor has been proposed as a potential solution for this problem. The donor airway’s original cells are initially removed in order to avoid giving the recipient immunosuppressive medication, and then repopulated with the recipient’s own cells.

This study focuses on determining if the original stiffness and structure of this airway will be maintained despite the removal of its original cells. This significantly advances the current area of research, as this will ensure that further narrowing and scarring does not happen following airway transplantation.

Dr. R. Holtby
Sunnybrook Health Sciences Centre

Impact of autologous platelet rich plasma on enhancing repair of rotator cuff tendons: A multicentre, randomized controlled trial

Rotator cuff tears are common and cause significant pain and disability. Despite advances in rotator cuff surgery, there is still a significant incidence of residual weakness and recurrent cuff tears after surgery. As a result, recent studies have focused on biologic enhancement of the healing process. One way of enhancing healing is through the use of Platelet Rich Plasma (PRP), a fraction of the patient’s own blood which is rich in growth factors. Based on studies of other pathologies, the investigators expect better rotator cuff healing with the use of PRP following arthroscopic rotator cuff surgery.

The results of this innovative study will add to the state of knowledge by providing evidence on whether augmentation of rotator cuff repair with biological factors is an effective way of improving health-related quality of life.

Dr. T. Joy
University of Western Ontario

Sitagliptin for the treatment of non-alcoholic steatohepatitis in patients with type 2 diabetes

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in both adults and children in the western world. The spectrum of NAFLD ranges from simple fat deposition in the liver to a more aggressive form called non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis. ~50% of patients with type 2 diabetes (DM2) have NAFLD. Moreover, those with DM2 often have more severe NASH, primarily attributed to insulin resistance (IR), the phenomenon where the body is unable to appropriately use available insulin. Mortality from cardiovascular disease (CVD) is significantly increased among those with NAFLD/NASH. Currently there are no specific therapies for NASH, and medications that have been tried either cause weight gain or are contraindicated in significant liver disease.

Sitagliptin is a new medication for DM2. It has several beneficial effects such as improving insulin secretion, being weight neutral, having a low incidence of hypoglycemia, and being safe in individuals with significant liver dysfunction. Based on these and other effects, sitagliptin may be a potentially useful therapy for patients with both DM2 and NASH.

This study will evaluate the effects of sitagliptin on liver disease and hormones and parameters related to IR and CVD risk in patients with DM2 and NASH.

Dr. K. Khalili
Mount Sinai Hospital

Detection of occult bowel hemorrhage using gadofosveset trisodium-enhanced MRI

Bowel hemorrhage usually occurs from the stomach or colon, parts of the bowel that are accessible by endoscopy. However, in some patients the site of bleeding remains unknown after endoscopy. Unfortunately, there is no reliable single method of detecting the site and cause of bleeding in these patients, who then undergo multiple, and often invasive, examinations.

The investigators have devised a method of bowel imaging with MRI using gadofosveset trisodium, a unique new contrast agent. Gadofosveset trisodium, unlike all other MR and CT contrast agents, remains in blood circulation for up to one hour, allowing for long observation and time for the agent to accumulate at the bleeding point. It is advantageous to other tests in that it is non-invasive, has no radiation, and has less associated risk. In this pilot study, the investigators will determine whether gadofosveset-MRI is acceptable to patients and technically feasible. If successful, a large-scale study will be designed to determine if gasofosveset-MRI can replace the current battery of tests performed to diagnose the cause of bowel hemorrhage.

Dr. P. Luke
University of Western Ontario

Dendritic cell therapy combined with soluble CD83 to prevent allograft rejection

Although transplant survival has improved over the past two decades, the long-term side effects of immunosuppression lead to cancer, infection and transplant damage. Recently, biologic therapies have been explored in order to improve immunotherapy by reducing rejection rates and limiting of immunosuppressive drugs required. Antigen-presenting cells called dendritic cells (DCs) have been shown to modify immune responses. Infusion of immature DCs can make the host’s immune system unresponsive to the transplanted organ, whereas mature DCs can cause transplant rejection.

This study aims to improve transplant survival through transfusion of immature DCs, along with an agent called sCD83 that prevents the DCs from becoming mature within the transplant recipient. The immature DCs will then be able to prevent transplant rejection and prolong transplant survival.

Dr. M. Nadeau
Dr. C. Bailey
University of Western Ontario

Soft tissue injury model of the cervical spine following unilateral facet dislocation

Unilateral facet injuries are relatively common in the sub-axial cervical spine. They include a spectrum of injuries, such as subluxations, dislocations and fractures; however, the range of instability varies greatly depending on the pattern of injury produced. Hence, the treatment for unilateral facet dislocations is variable and there is little in the way of established guidelines to direct and describe the most appropriate treatment. This is partially due to a lack of biomechanical studies focused on evaluating changes in spinal stability following various injury patterns. The extent of anatomical disruption secondary to unilateral facet injury is poorly understood, and few studies have been able to quantify the associated instability. This knowledge would allow physicians to better evaluate which treatment is most appropriate.

The objective of this study is to create an experimental model representing a unilateral facet dislocation of the spine. The nature of this injury is poorly understood, and improving knowledge surrounding the injury mechanism will ultimately lead to improved treatment.

Dr. A. Niazi
Toronto Western Hospital

The use of web-based interactive 3D anatomic models for teaching ultrasound guided neuraxial nerve blocks

Neuraxial nerve blockade is the technique of blocking nerve activity in the spine with local anesthetics to prevent pain during surgery, or relieve chronic pain. Neuraxial blocks are challenging, as the needle must be inserted between the bones of the spine to reach the spinal cord and nerves. Recently, ultrasound has been used for checking the spinal anatomy before the block, and guiding the needle insertion, reducing the time and number of attempts to achieve successful nerve blocks. This use of ultrasound introduces a new skill in delivering neuraxial blockade, creating a need for new teaching aids for physicians learning this skill.

Translating the two-dimensional ultrasound images into the three-dimensional anatomical structures of the spine is difficult. To allow students to understand the anatomic structures seen in ultrasound images, this study will create an online teaching module synchronizing video recording of the spinal ultrasound images with three-dimensional anatomical models of the structures seen in the ultrasound images. Ultimately, the module will be made freely available on the Web for medical educators and physicians being trained around the world.

Dr. N. Paul
Dr. P. Rogalla
University Health Network

The impact of obesity on image quality and patient radiation dose during thoracic computed tomography

Canadian obesity adds additional strains to an overburdened health care system. Increasing tube kilovoltage and current required for larger subjects causes significant increases in patient radiation dose and potential increased risk of harmful irradiation side effects. This is particularly evident in computed tomography (CT) due to the dramatic increase in utilization of relatively high dose protocols in CT coronary angiography and CT pulmonary angiography. Assessment of patient radiation dose is complicated, and currently there is no convenient, accurate or robust strategy for assessment of patient dose associated with a particular protocol.

The two primary objectives of this study are a) to determine the influence of obesity on radiation dose and image quality of thoracic CT; and b) to establish dose thresholds at different body mass indices that maintain conspicuity of lung lesions. This study will generate accurate evidence-based data to provide a gold standard that will be used to establish required radiation dose thresholds for diagnostic thoracic computed tomography and to compare different protocols.

Dr. D. Piquette
Sunnybrook Health Sciences Centre

Guided acute resuscitation: Does education depend on trainees’ interactions and participation? (The GUARDED TIP study)

Patient safety concerns and increased patient acuity have re-shaped postgraduate medical training conditions. These changes have put pressure on senior physicians supervising residents’ clinical activities to get more involved in patient care. Direct supervisor involvement, by altering the nature of the supervisor-trainee interactions and resident participation in patient care, could affect resident learning.

The main objectives of this qualitative study are to better understand: 1) how a closer level of supervision during acute resuscitation episodes affects the interactions between the residents, their supervisors, and their clinical environment; and 2) how these changes affect resident understanding of specific resuscitation episodes. The study will identify factors that could be targeted by educational interventions in order to optimize resident learning when patient safety forces supervisors to directly intervene in patient care.

Dr. D.B. Rootman
Dr. H. Yucel
St. Michael’s Hospital

Cavernous hemangioma of the orbit as vascular malformation: Clinical features, imaging, histology, histogenesis and flow dynamics

Cavernous hemangioma has been defined as a “benign, slowly enlarging encapsulated neoplasm”. It is often considered the most common benign orbital neoplasm in adults, representing approximately 5% of all orbital tumours. Despite the designation as a benign neoplasm, a closer look at the comparative histology, imaging characteristics and clinical behaviour of cavernous hemangioma tends to dispute this notion.

The purpose of this investigation is to present a thorough clinical-radiologic-pathologic description of cavernous hemangioma in order to confirm their nature as non-neoplastic, and reconcile these entities with modern literature concerning vascular malformations. Through a description of their clinical behaviour, flow characteristics and histopathologic features, this study intends to firmly place orbital cavernous hemangiomas within the wider classification of vascular malformations. The ultimate goal of the research is to foster interdisciplinary research, communication and understanding in order to better identify and manage slow flow vascular malformations in general, wherever they may occur in the body, and thus to improve diagnosis and management for a wide range of patients.

Dr. R.F. Spitzer
Hospital for Sick Children

Use of ACASI to gather information on risk behaviours in a referral population of pregnant Canadian adolescents

The Hospital for Sick Children has a specialized, multidisciplinary program to care for pregnant adolescents. It has been noted that many of these patients are involved in high risk social behaviours, be they related to consumptions, abuse or exposure to violence. Anecdotally, it is found that many of these behaviours do not come to light unless a crisis develops, despite a thorough history-taking at initial presentation.

The investigators propose to use a novel interviewing methodology, ACASI (auto computer-assisted self interview) which is self-administered and therefore removes the perceived stigma of a traditional interview, and to compare the responses received to those obtained in the traditional history taken at the first encounter with the pregnant teen. ACASI has been known to elicit more evidence of stigmatized behaviours in an adolescent population than traditional interviewing methods. The findings from this study could have widespread implications to improve the care and programs offered to pregnant adolescents, to minimize their risk behaviours and improve their and their children’s health.

Dr. K.C-Y. To
Dr. C.M. Clase
McMaster University

Oral cholecalciferol (Vitamin D3) therapy in prevalent hemodialysis patients: A randomized placebo controlled pilot study

Vitamin D is a prohormone obtained from diet and sun exposure that is activated sequentially by a two-step hydroxylation reaction in the liver [to 25(OH)D] and in the kidney via 1?- hydroxylase to the active hormone, calciferol [1,25(OH)2D]. Besides the kidney, many other tissues express 1?- hydroxylase activity capable of Vitamin D activation. This local tissue activity is important for maintenance of health and relies on adequate circulating 25(OH)D levels. Not only are dialysis patients deficient in the active form of Vitamin D due to kidney failure, but they are also deficient in its precursor, 25(OH)D. Low levels of 25(OH)D have been associated with higher rates of death and cardiovascular disease both in the general population and in patients with renal failure. Despite this, there is a lack of randomized controlled trials (RCTs) examining the effects of nutritional Vitamin D in dialysis patients.

The investigators hypothesize that long-term supplementation with nutritional Vitamin D in dialysis patients reduces mortality and cardiovascular outcomes. Before embarking on a large scale RCT, this small pilot study will be undertaken with the goal of determining the feasibility and barriers to successful randomization and adherence to treatment protocols which will inform subsequent studies, as well as the effect of cholecalciferol compared with placebo in raising serum Vitamin D levels.

Dr. K.N. Vogt
Dr. N. Parry
University of Western Ontario

The use of gentamicin-impregnated collagen implants to prevent surgical site infection in colorectal surgery: A randomized controlled trial

Surgical site infections (SSIs) are the most common nosocomial infection among surgery patients, and can have a significant impact on both patients and resources. Despite best practices, SSIs will occur after 10 – 35% of colorectal surgeries. The use of implants containing a high concentration of antibiotic delivered to the local surgical site has been previously suggested to reduce the rate of SSI.

This trial is being undertaken to determine if the use of a gentamicin-impregnated collagen implant left at the surgical site can reduce the incidence of SSI in patients undergoing elective colorectal resection. If this intervention is shown to be effective in the prevention of SSI in this high risk population, significant benefit with respect to both patient morbidity and resource utilization may be achieved.

Dr. K.W-Y. Wong
Dr. C.R. Forrest

CLEFT-Q: Development of a patient-reported outcome measure for cleft lip and palate

Patients with cleft lip and palate (CLP) undergo a series of procedures from birth to adulthood aimed at improving function and appearance. Outcomes of the treatment process have typically been assessed objectively by the health care team. Appearance and function have significant impact on quality of life (QOL) as interpreted by the patient and this should be an important indicator of treatment success, but there currently is no dedicated patient-reported outcome measure (PROM) for patients with CLP.

The goal of this study is to complete the first step in the development of a PROM to assess QOL and satisfaction with care in pediatric patients with CLP. The steps required to develop a PROM have been outlined in guidelines accepted by the Scientific Advisory Committee of the Medical Outcomes Trust. The three main steps are: 1) item generation; 2) item reduction; and 3) psychometric evaluation or validation of the instrument. This study aims to complete the first step, item generation, which involves data gathering through a literature review, qualitative interviewing with patients, and expert opinion.

Dr. V.T. Yin
Dr. P. Kertes
Sunnybrook Health Sciences Centre

Antibiotic resistance of ocular surface flora after continued use of topical antibiotics post intravitreal injection

There is currently no established standard of care for the use of prophylactic antibiotic post intravitreal injection for the treatment of Wet Age-Related Macular Degeneration (ARMD). The majority of ophthalmologists currently advocate for 3 days of topical fluoroquinolone (Vigamox or Zymar) post injection. However, in view of the need for monthly re-treatment in Wet ARMD, the danger of developing more resistant organisms may lead to antibiotic resistant endophthalmitis.

The purpose of this study is to determine if antibiotic susceptibility of the ocular surface flora changes after repeated use of topical antibiotics for 3 days post intravitreal injection in treatment of Wet Age-Related Macular Degeneration. The investigators expect to show that with repeated monthly topical antibiotic use there is an increase in antibiotic resistance of ocular surface flora.

January 1 to April 1, 2010

The Foundation approved grants with a total value of $694,300 in the first quarter of 2010, for the following projects:

Dr. E. Anagnostou
Bloorview Kids Rehab

A pilot, does finding study of pioglitazone in children with ASD

Autism is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors/restricted interests. Its etiology is not clear, although genetic factors seem to play an important role. In terms of the neurobiology of the disorder, in addition to structural changes related to connectivity, investigators have reported abnormalities in inflammatory responses and oxidative stress.

Pioglitazone is a Peroxisome Proliferator-Activated Receptor (PPAR) agonist: it is indicated for the treatment of type II diabetes, given its ability to modulate insulin sensitivity. Recent data also suggests that pioglitazone dampens microglia activation in the brain and decreases pro-inflammatory cytokines, as well as reduces oxidative stress and promotes mitochondrial biogenesis. As such, it may be a promising compound for the treatment of children with autism.
A case series has reported some favourable effects. Pioglitazone was listed as one of the medications requiring further assessment at the IACC update. There are currently no pioglitazone studies for autism listed at Clinicaltrials.gov. This investigator propose a pilot, single blind, dose finding study of pioglitazone in children with autism with the ultimate goal of identifying appropriate dosing and outcome measures for a follow-up larger placebo controlled clinical trial.

Dr. C. Birken
Hospital for Sick Children

PROMOTE: Preschoolers at Risk-Obesity and Cardiometabolic Risk Factors: Towards Early Identification

Over 25% of preschool children in Canada are overweight or obese, and the metabolic syndrome comprises a cluster of factors including obesity, abnormal insulin, blood pressure, and cholesterol that is associated with diabetes and heart disease in adulthood. Cardiometabolic factors in adolescents were shown to increase risk of diabetes in adults, and large gaps in knowledge exist on these factors in preschool children.

The objectives of this study include to characterize cardiometabolic factors in preschool children, understand the relationship between these factors and obesity, and the influence of familial/lifestyle factors on these relationships. Early identification of these factors in young children can lead to directed obesity prevention interventions.

Dr. D.J. Cook
Dr. M. Trymainski
University Health Network

Differential gene expression in the non-human primate and rat: whole genome differential gene expression in the immediate-early phase following stroke

Stroke has been successfully treated using several therapies in rodent and lissencephalic primate models but not gyrencephalic primates or humans. One reason for this difference may be a difference in the molecular response to stroke in each species. To elucidate the differences in gene regulation between species in the immediate and early phases following stroke, these investigators propose a comparison of responses utilizing whole genome microarrays over a time course.
Differences in gene regulation following stroke identified in this project may provide an explanation for the discordant results in rodents and humans; furthermore, these differences may act as putative targets for stroke therapy to be explored in the future.

Dr. M.S. Freedman
Hospital for Sick Children

Is Electrolyte Maintenance Solution Administration Required in Low-Risk Children with Gastroenteritis?

Gastrointestinal infections account for approximately 150,000 outpatient visits and 20,000 hospitalizations annually amongst Canadian children under five years of age. Oral Rehydration Therapy (ORT) is routinely recommended for low risk children with minimal/mild dehydration, which includes the use of an Electrolyte Maintenance Solution (EMS) to replace all losses. No clinical evidence, however, exists that it is necessary to use EMS in low-risk children with minimal/mild dehydration. The cost of EMS combined with its poor palatability may act as a barrier to adequate fluid intake.

This study aims to determine if the treatment failure rate in low-risk children who present to an Emergency Department with minimal/mild dehydration is higher amongst children who are advised to perform ORT with their favourite liquids compared to those who are encouraged to replace losses with an EMS. Secondary outcomes include present weight change at follow-up, proportion receiving intravenous hydration, proportion hospitalized, and frequency of diarrhea and vomiting episodes.

Dr. R. Ilan
Queen’s University

Video-based study of communication during handovers: How do intensive care physicians use SBAR?

Hospital handovers are crucial and commonplace, and health professionals must frequently exchange information about, control over, and responsibility for their patients. Communication breakdowns during handovers have been associated with patient harm and system inefficiencies.

To improve patient safety, research groups and patient safety organizations have already been promoting handover best practices. In particular, using standardized procedures such as - SBAR, a mnemonic reminding participants that every handover should include the patient‘s Situation and Background, and the clinician‘s Assessment and Recommendation, have been recommended worldwide. However, using SBAR has never been shown to improve handover‘s effectiveness or patient safety. Furthermore, it is remarkable how little is known that could provide a basis for improving handover practices.

This investigator recently created a corpus of digital video to be used for physician handover research. In a preliminary study, Dr. Ilan found that experienced physicians did not consistently cover SBAR elements in their handovers.

The objective of this study is to expand current understanding of communication during handovers between experienced intensive care unit physician, and it will determine the structure and content of handovers, in particular the presence of SBAR elements.

Dr. M. Lines
Dr. K. Boycott
University of Ottawa

Gaining insight into human craniofacial development through the identification of a novel gene for mandibulofacial dysostosis

Mandibulofacial dysostosis (MFD) is an inborn error of craniofacial development with important surgical and cosmetic implications for patients, and it is characterized by underdevelopment of the facial bones, jaw, and ear canals, and is the key finding in Treacher Collins syndrome (TCS)- a common genetic condition. MFD is also a feature of other syndromes for which the responsible genes have not yet been identified.

These investigators have characterized a new syndrome in ten patients, in whom MFD is associated with growth retardation, microcephaly, developmental delay, cleft palate, and characteristic ear anomalies (MFD with microcephaly; MFDM). To date, the gene responsible for MFDM remains unidentified; however, using genomic microarray analysis, Drs. Lines and Boycott have determined that one of ten patients with MFDM has a complex rearrangement involving gains and losses of DNA from submicroscopic regions of chromosomes 17q21 and 4p12. The 17q21 region involved contains multiple genes, including several plausible candidate genes for this disorder; the 4p12 region contains no genes.

In this study, the investigators propose sequencing of candidate genes within the 17q21 critical region with the aim of defining the genetic lesion responsible for MFDM. This will allow clinical mutation testing in this expanding patient population, and it will further current understanding of brain and skull development.


Dr. M. Selzner
University Health Network

Ex Vivo Human Liver Perfusion: Assessment and Repair of Marginal Liver Grafts for Transplantation

The increasing demand for liver transplantation has resulted in a dramatic organ shortage with a waiting list mortality exceeding 20%. An attractive strategy to increase the availability of liver grafts is the use of marginal livers, such as fatty livers and livers from older donors. The use of these grafts for transplantation is currently limited since the current cold static preservation technique does not allow the estimation of graft function and injury and is not suitable to induce repair mechanisms.

This investigator has developed a novel model of normothermic ex vivo liver perfusion, which allows the preservation of livers at physiologic temperatures (37°C) with intact cellular metabolism. This model allows the investigator to determine liver function and graft injury prior to transplantation. In addition, it offers the unique possibility to induce repair mechanisms and the potential to restore the quality of marginal grafts ex vivo.

The aims of this study are to use normothermic ex vivo perfusion of human livers as a novel technique for liver preservation, assessment, and organ repair and define markers of graft injury and function that predict post transplant outcome. In addition, during ex vivo perfusion Dr. Salzner will inhibit mediators of cell death to decrease liver injury at the time of reperfusion.