Foundation Funded Projects for 2013

 

October 1 to December 31, 2013

July 31 to September 30, 2013

April 1 to June 30, 2013

January 1 to March 31, 2013

 

October 1 to December 31, 2013

 

 

Dr. M. Carter
Hospital for Sick Children

Investigating the "Two-Hit Hypothesis" for neurodevelopmental disorders associated with recurrent copy number variants 22q11.2 microduplication and 15q11.2 microdeletion

Copy number variants (CNVs) are found in everyone’s DNA. They are extra or missing pieces of genetic information. It is known that some CNVs are harmless, and some cause human disease and/or neurodevelopmental or psychiatric disorders (for example, attention deficit-hyperactivity disorder, autism spectrum disorder, depression).

In this proposal, two specific CNVs are being studied: a small deletion (missing piece) of chromosome 15 and a small duplication (extra piece) of chromosome 22. These two CNVs are found more often in people who have medical or neurodevelopmental problems than in people without these problems. Yet, enough is not known about the people who have them. If these people are studied, we will learn more about what they are at risk for. This will help doctors give accurate information to parents when their child is diagnosed with one of these CNVs.

People can have many different types of CNVs in their DNA. This team will also study whether having more CNVs, or particular CNVs, influences what medical, developmental and psychiatric problems these people have. It is suspected that a relationship between having more CNVs and having more problems will be found.

 

 

Dr. M.M. Chiavaras
McMaster University

Impact of platelet rich plasma over alternative therapies in patients with lateral epicondylitis (IMPROVE): a multicenter, randomized trial comparing autologous platelet rich plasma (PRP) versus autologous whole blood versus dry needle tendon fenestration on pain and quality of life in patients with lateral epicondylitis

Lateral epicondylitis (LE) or “tennis elbow” is the most common cause of lateral elbow pain, affecting up to 15 million people in North America and an estimated 405,177 Ontarians. LE leads to high morbidity and absence from work. The costs associated with LE are enormous and include lost productivity from work and health care costs. Many treatment options exist however they lead to conflicting results with no clear consensus on the optimal treatment.

Autologous blood concentrates (i.e. Plasma Rich Protein or PRP) for the treatment of tendinosis have been shown to increase the concentration of growth factors to the region, potentially augmenting the natural healing process. PRP has become a multimillion dollar industry; however, there is no definitive evidence that it is more effective than cheaper therapeutic alternatives. A randomized controlled, blinded, 4-arm pilot study is proposed comparing PRP, whole blood, dry needle fenestration, and physical therapy exercises alone.

Primary outcome measures for the 2 year pilot study are to demonstrate feasibility of recruitment and adherence to the protocol. Findings from this pilot study will be used to guide the sample size required for a larger trial that will provide definitive evidence on the optimal treatment for tennis elbow.

 

 

Dr. N. Dudek
University of Ottawa

Feedback to supervisors: is anonymity really so important?

Feedback is an essential part of learning. Physicians teach medical learners during the clinical component of their training by providing supervision. Physicians receive assessments on the quality of their clinical supervision from trainees. These assessments make up the majority of feedback that physicians receive. They are encouraged to use this information to improve their teaching performance.

Research has identified several features of effective feedback that suggest an open process. However, the majority of feedback provided to clinical supervisors is anonymous given concerns regarding feedback provision to someone in a position of power. Evidence for and against anonymous feedback is limited and does not strongly suggest one over the other. To our knowledge no medical school or residency program with an open feedback system has been systematically studied to look at the advantages and disadvantages of such a system. The University of Ottawa’s Physical Medicine and Rehabilitation Residency Program uses an open approach for resident-to-faculty feedback.

The objective of this project is to describe the strengths and weaknesses of open feedback. The University of Ottawa’s PM&R program will be used as a holistic, single-unit case study within which open feedback will be studied using qualitative methodologies.

 

 

Dr. N. Duggal
Dr. M. Goodale
Western University

Neural plasticity associated with the loss and recovery of vision in patients with pituitary tumours before and after medical or surgical intervention

Visual loss is a significant health problem in Canada and its incidence is rising. In 2007, it affected 2.5% of Canadians at a cost of $15.8 billion and is expected to increase to 4.0% by 2032. The goal of the proposed study is to use functional magnetic resonance imaging (fMRI) to explore the potential for brain recovery in patients with reversible visual loss.

Pituitary tumours, a prevalent problem affecting 0.2% of the population, provides a unique model of reversible visual loss. The optic chiasm, located immediately above the pituitary gland, can be subjected to mechanical compression by pituitary tumors resulting in visual loss. Visual outcomes following treatment can be unpredictable, depending on the degree to which the visual pathways have undergone reversible versus irreversible injury.

The proposed project will chart neural plasticity related to visual injury and recovery before and after surgical or pharmacological intervention in patients with pituitary tumors using fMRI and visual field perimetry. Our goal is to utilize cutting edge imaging techniques to develop non-invasive prognostic tests that will be used to further tailor the treatment of visual dysfunction in individual patients and be applied broadly to patients suffering from a variety of diseases.

 

 

Dr. E. Fan
Mount Sinai Hospital

The importance of spontaneous breathing efforts in mechanically ventilated patients with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a devastating illness that results in the loss of normal lung function, and these patients often require life support with a breathing machine (i.e., respirator) to support their breathing. Currently, there are no medications for this syndrome, and the only beneficial treatment is setting the respirator to deliver small breaths to the damaged lungs. The use of an artificial respirator for the intentional and controlled delivery of small breaths is often uncomfortable for patients, and they require sedatives/pain medications to prevent them from taking their own breaths.

Alternatively, newer respirators can deliver partial assistance, allowing patients’ to take their own breaths (spontaneous breathing). Spontaneous breathing may also improve blood pressure, oxygen levels, and result in less weakness of the breathing muscles; however patients receiving partial assistance from the respirator may have larger breaths, and offset any benefits of enhanced comfort and lower sedative/pain medication requirements.

This study will determine whether the larger breath sizes during spontaneous breathing on the respirator is associated with important harms in patients with ARDS. The results of this study will help clinicians to determine the safest way to use the respiratory to manage these sick patients.

 

 

Dr. Z. Friedman
Mount Sinai Hospital

Challenging authority during a life threatening crisis: the effect of a teaching intervention adapting aviation safety to medicine: using "Cockpit/Crisis Resource Management" for challenging critical errors by a superior

Effective communication during acute situations can easily break down when different levels of authority within the team are involved. Aircraft crashes which were traced back to similar teamwork failures led to the genesis of “Cockpit Resource Management” (CRM) to train crews to “speak up” when safety concerns arose. This study aims to assess the effect of a targeted CRM based teaching intervention on residents’ ability to effectively challenge clearly wrong clinical decisions made by their staff.

This will be a mixed methods (quantitative and qualitative) study. Second year anesthesia residents will be recruited and randomized to receive a targeted CRM based teaching intervention or a control group which will receive a general teaching session for crisis management. The teaching intervention was designed based on input from 50 resident interviews and contains 4 CRM based communication tools. Subjects will then participate in a simulated crisis (disconnected from the teaching session) that presents them with opportunities to challenge a staff regarding a clearly wrong decision in a life threatening scenario. Sessions will be video-recorded and assessed by 2 blinded assessors.

Positive findings will result in changing the residency curriculum to address the problem of challenging authority and incorporating the tools used in the intervention.

 

 

Dr. S. Husain
University Health Network

Comparison of galactomanan in exhaled breath condensate and bronchoalveolar lavage for pulmonary invasive aspergillosis in immunocompromised individuals

Fungal infection especially mold infections called Aspergillus is the most common and second most common invasive fungal infection in bone marrow transplant (BMT)/acute leukemia patients and solid organ transplant (SOT) recipients respectively, causing death in 38% of infected patients. Its diagnosis using traditional microscopy and culture has a sensitivity of 43%; however a newer diagnostic test which detects a component of Aspergillus called galactomannan showed promise with sensitivity of 88% and 42% in lung fluid (bronchoalveolar lavage fluid – BAL) and blood respectively.

Bronchoscopy for obtaining BAL is an invasive procedure that has a low but significant risk. Recently exhaled breath condensate (EBC), a non-invasively collected sample is being considered instead. The objective of the study is to assess the equivalence of the diagnosis of Aspergillus infection using galactomanan test from BAL and EBC. The optimal cut-off value for galactomannan in EBC will be evaluated before assessment.

Informed consent will be obtained from clinically stable BMT, SOT recipients and acute leukemia patients undergoing bronchoscopy, who are > 18 years and are able to consent. 434 samples of BAL and EBC will be collected and tested for galactomannan. >=90% similarity is anticipated between EBC and BAL galactomannan for diagnosis of Aspergillus infection.

 

 

Dr. J. Laffey
St. Michael’s Hospital

Determination of the therapeutic potential of human mesenchymal stem/stromal cells for sepsis induced ALI/ARDS

When people become critically ill, such as during severe infection, their lungs often fail – this is termed Acute Respiratory Distress Syndrome (ARDS). ARDS is common, and often fatal, with over 30,000 new sufferers annually in Canada. Mortality remains high, comparable to that seen from HIV infection, breast cancer, and asthma, while ARDS survivors subsequently experience a poorer quality of life.

There is no therapy for ARDS and novel therapies are urgently required. Mesenchymal Stem/Stromal Cells (MSC’s) offer significant hope for ARDS and early findings in disease models are promising; however much remains to be learned. The best dosage regimen is not known, while our understanding of the mechanism of MSC action is also unclear. In addition, the ‘therapeutic’ potential of hMSCs, i.e. whether they are they effective when after the lungs are injured, is unclear. Lastly, safety concerns regarding MSCs need to be addressed.

This project is designed to address these questions, so that we can move forward to determining whether MSC’s are effective in actual ARDS sufferers. If successful, stem cell therapies would help save the lives of these sufferers, improving the quality of life of survivors and potentially reduce healthcare costs.

 

 

Dr. D.N. Levin
Dr. A. Hong
St. Michael’s Hospital

A randomized controlled trial of Cesamet (nabilone) for the prevention of postoperative nausea and vomiting in elective outpatient surgery

Untreated, one third of patients undergoing general anesthesia will have postoperative nausea, vomiting, or both (PONV). Patients often rate PONV worse than postoperative pain. PONV increases the risk of aspiration, dehiscence, esophageal rupture, and pneumothoraces. PONV delays discharge, and is the leading cause of unexpected admission after ambulatory surgery. The annual cost of PONV in North America is estimated to be several hundred million dollars. Although strategies exist, there is no known intervention that works for the complete prevention of PONV.

Nabilone is a synthetic cannabinoid currently in use to prevent nausea and vomiting in patients receiving chemotherapy. There is evidence showing efficacy, safety, and tolerability of nabilone in this population. There has been success in the past translating treatments for chemotherapy-induced nausea and vomiting to use in the perioperative environment.

It is hypothesized that nabilone, given prophylactically, will lower the incidence of PONV. This proposal includes a double-blind, randomized, placebo-controlled trial of nabilone for a new application in the prevention of PONV in elective outpatient surgery; furthermore nabilone may have secondary benefits in reducing postoperative pain. If efficacious, nabilone would be a valuable tool for the prevention PONV, with the potential to significantly improve morbidity, costs the patient experience related to anesthesia.

 

 

Dr. M.H. Livingston
Dr. S. Jones
Western University

Novel assessment of ingrown toenails treated by excision of the skinfold rather than toenail (NAILTEST): a prospective cohort study of the Vandenbos procedure in children and adolescents

The purpose of this project is to assess the effectiveness of a surgical procedure for ingrown toenails. Ingrown toenails are a common problem in the general population. There are many non-surgical treatments, such as soaking, wearing loose shoes, antibiotics, and specialized braces. Still most people with ingrown toenails eventually need surgery. The most common surgical procedure involves removing all or part of the toenail as well as destroying part of the underlying nailbed. This prevents reoccurrence (where the toenail becomes ingrown again).

In 1959, Vandenbos and Bowers described a procedure that left the nail and nailbed in place and excised the skin only. Two recent studies from Ontario have sparked renewed interest in this technique when they reported a reoccurrence rate of zero. This study seeks to see if these results can be replicated when patients are treated by surgeons and then assessed by a different person after surgery.

This study will also determine infection rate, bleeding, formation of excessive scar tissue, altered growth of the toenail, healing time, length return to activities, cosmetic result, and patient satisfaction. The participants in this study will be adolescents treated by a group four Pediatric General Surgeons in London, Ontario.

 

 

Dr. D. Orlich
Dr. J. Sherbino
McMaster University

Does a just-in-time mobile simulation module improve success and time to completion in surgical cricothyroidotomy?

This study will aim to evaluate the utility of a 90 second just-in-time learning video that details the knowledge and skills necessary for proper surgical cricothyroidotomy, on improving time to completion and correct tube placement in a porcine cadaver.

It will be a randomized control study involving emergency medicine residents and staff. Control participants will not receive any instruction prior to being asked to perform surgical cricothyroidotomy on a porcine neck specimen, while intervention group participants will be shown the just-in-time learning video before the same simulation. The simulation session will be timed from initial skin contact to insufflation of a balloon attached to the porcine trachea. After completion, the specimen will be dissected to determine correct tube placement.

The aim is to enroll 74 subjects, which will give a power of 86.7% to detect an improvement from 90 to 60s in mean placement time and a power of 80% to detect an improvement from 70 to 95% for successful placement. Regression analysis will be used to compare subgroups based on age, year of study or time spent as faculty, and prior cricothyroidotomy exposure, to determine if the intervention had different effects on each subgroup.

 

 

Dr. A. Tucker
Dr. R. Bicknell
Queen’s University

Treatment of adhesive capsulitis: a randomized placebo-controlled trial comparing arthrographic joint distention with steroid and local anesthetic versus arthrographic joint distention with local anesthetic alone

Frozen shoulder or adhesive capsulitis is a common cause of shoulder pain, estimated to affect 25% of the general population. Many forms of treatment have been advocated for frozen shoulder including physiotherapy, injection with steroid, distension arthrogram with steroid, manipulation under anesthetic and arthroscopic releases. There is no general agreement in favour of one form of treatment, and the response to a particular treatment varies in different series.

A few randomized controlled trials appear in the literature. Most of these showed improvements with steroid use, but the results were not always statistically significant. One randomized control trial reported superior results in favor of arthrographic joint distension with steroid compared to a saline placebo. It is believed there have been no other similar randomized trials to support these results.

The objective of this study is to determine if arthrographic distension of the shoulder joint with steriods is an effective treatment modality for adhesive capsulitis as compared to injection with local anesthetic and contrast alone. The study design is a placebo-controlled, double blind clinical trial where participants will undergo distension arthrogram of the shoulder and be randomized to receive either Triamcinalone (steroid), lidocaine and contrast or injection with lidocaine and contrast alone.

 

 

Dr. M.E. Wilcox
Dr. G. Rubenfeld
Sunnybrook Health Sciences Centre

COGWELL: COGnitive outcomes and WELLness in survivors of critical illness

As survival rates from critical illness improve, strategies to return patients to their baseline cognitive and functional status are important research priorities. Upwards of 9 out of 10 ICU survivors will suffer some degree of cognitive impairment at hospital discharge and approximately half will have decrements that persist for years. While the mechanisms for this newly acquired brain injury are poorly understood, several risk factors have been identified. Unfortunately, it is unclear how to accurately predict long-term cognitive impairment.

Immediate opportunities to improve cognitive outcomes through risk reduction exist. This proposal is to study comprehensively the prevalence of sleep abnormalities and their association with cognitive impairment, as it may yield potential targets for effective therapy; moreover we will examine a well-known genetic risk factor for dementia [APOE 4] that may allow for genetic risk stratification of ICU survivors at greatest risk of cognitive impairment. It is hypothesized that EEG [an established longitudinal marker of brain dysfunction] is a novel and independent predictor of long-term cognitive impairment, and possibly a candidate intermediate end point for future clinical trials.

This study has the potential to identify novel biomarkers and risk factors for post-critical illness cognitive impairment, and will lay the foundation for strategic development of interventions to reduce risk in vulnerable ICU survivors.

 

 

Dr. R. Wu
Dr. R.P. Boushey
University of Ottawa

The evaluation of a rectal cancer decision aid and the factors influencing its implementation in clinical practice

Colorectal cancer is the third most common cancer in North America. Rectal cancer presents a particular challenge to surgical management given the pelvic anatomy and presence of two surgical alternatives for resection of the tumour. Traditionally the decisions on surgery have mostly been dependent on the surgeon. Studies have shown that greater patient involvement in decision making may lead to higher quality decisions congruent with patient values.

To enhance patient involvement in the decisions of rectal cancer surgery, a patient decision aid (PtDA) was developed following the guidelines of the Ottawa Decision Support Framework (ODSF), a well validated framework that directs decision aid development, evaluation and implementation. The rectal cancer PtDA provides patients with evidence-based information on the risks and benefits of the two surgical options and help patients to make decisions aligned with their values and preferences.

Since development, the decision aid has not been formally evaluated. The current study will be the next stage in 1) evaluating the effect of the rectal cancer PtDA on patients’ choice and decision making process through a before and after study, and 2) exploring the facilitators and barriers of implementing the PtDA into a colorectal cancer clinical setting as perceived by the surgeons and nurses through a web-based survey.






July 1 to September 31, 2013

 

Dr. H. Abrams
Dr. C. Bell
University Health Network

The Isolation Project: evaluating the impact of isolation precautions on systems outcomes and cost of care

A retrospective cohort study will be conducted to investigate the impact of isolation precautions on consecutive General Internal Medicine patients who were admitted to three academic hospitals – Toronto General Hospital, Toronto Western Hospital and Mount Sinai Hospital – from January 2008 to December 2012.

The study can be divided into two components. For Part 1, cohorts will be matched on propensity score to evaluate the impact of patient isolation on systems outcomes such as 30-day hospital readmission rate, length of stay, standardized mortality ratio, selected patient adverse events and discharge destination. For Part 2, cohorts will be matched based on discharge diagnosis and Resource Intensity Weight to compare the cost of hospital care for isolated versus non-isolated patients.

Integrated and end-of-grant knowledge translation (KT) strategies will be used to promote the uptake of our research and improve the care of isolated patients. Knowledge of isolation as a risk factor for hospitalization-induced functional decline would encourage the development of novel interventions and risk-mitigation strategies for patients placed in isolation. In addition, these results could also influence institutional remuneration schemes so that hospitals are properly compensated, and therefore, able to fully care for isolated patients.

 

 

Dr. M. Bhandari
Dr. P.J. Devereaux
McMaster University

HIP fracture accelerated surgical treatment and care track (HIP ATTACK) trial

Worldwide millions of adults (>35,000 Canadians) annually suffer a hip fracture. Hip fractures primarily occur in the elderly and have devastating consequences. Many patients suffering a hip fracture will die or suffer a major complication within 30 days. There is preliminary evidence that suggests early surgical treatment of a hip fracture may improve patients’ outcomes; however, standard care in Canada is that most patients typically wait more than 24 hours to have surgery.

The study objective is to assess the impact of accelerated surgical care (i.e., goal of surgery within 6 hours of diagnosis) versus usual timing of surgery on the 30-day risk of a composite of major perioperative complications in adults with a hip fracture, in a randomized controlled trial. 260 patients will be randomized to receive accelerated medical clearance and surgery (goal of surgery within 6 hours of diagnosis) or standard care. Consenting patients aged >45 years, who are diagnosed during working hours on week days with a hip fracture requiring surgery will be included. Study personnel will follow patients throughout their hospitalization, at 30 days, and 1 year after surgery.

 

 

Dr. J. Catapano
Dr. G.H. Borschel
Hospital for Sick Children

Enhancement of nerve regeneration with aminopropyl carbazoles following nerve injury

Obstetrical brachial plexus palsy, which is more common than Down’s syndrome, can result in severe nerve injuries leaving the child with lifelong paralysis and numbness. Despite advances in surgical reconstructive methods, outcomes remain poor. Presently, we lack a pharmacologic means of improving recovery, and treatment of neonatal nerve injury remains surgical.

The spinal cord and peripheral nerves are the means by which the brain is able to transmit messages to control movement and receive signals from sensation. Motor neurons, residing within the spinal cord, and sensory neurons, residing just outside the spinal cord in the dorsal root ganglia, are necessary to this process. In rat studies, neonatal nerve injuries have been shown to cause death of 70% of neonatal neurons, impairing the ability for the peripheral nervous system to repair and regenerate. Preliminary studies have demonstrated the compound P7C3 to rescue neurons following nerve injury, resulting in dramatically improved muscle force, sensation, and functional recovery.

The objective of this study is to improve neuron survival by administering P7C3 after nerve injury and investigate whether improved neuron survival translate to improved behavioural and functional outcomes. These studies will be studied in a rat model as a direct patient surrogate and could offer new hope to newborns with nerve injury.

 

 

Dr. N. Ferguson
Dr. E. Fan
University Health Network

Strategies for optimal lung ventilation in ECMO for ARDS: The SOLVE ARDS Study

Artificial life support with a respiratory (ventilator) may be life-saving for patients with lung failure, especially those with the acute respiratory distress syndrome (ARDS); however in recent years, doctors have recognized that the ventilator itself can worsen lung failure, particularly in the sickest patients. As a result, there has been a growing interest in the use of an artificial lung device called extracorporeal membrane oxygenation (ECMO) for the management of patients with severe ARDS.

While being supported with ECMO, the lungs can rest and potentially avoid additional injury from the ventilator; however it is currently unclear how best to set the ventilator to minimize any further damage to the lungs of patients with severe ARDS supported with ECMO. This study will help to determine the optimal settings for the ventilator in these critically ill patients on ECMO to avoid any ventilator-induced lung injury (VILI).

The results of this study may help inform clinicians caring for patients with severe ARDS supported with ECMO on how to further improve outcomes in these patients.

 

 

Dr. N. Goldenberg
Dr. J. Laffey
St. Michael’s Hospital

The role of cystic fibrosis transmembrane conductance regulator and transient receptor potential channels in hypoxic pulmonary vasoconstriction

The lung is where oxygen enters the blood and carbon dioxide is removed. Normally, neither inhaled air nor blood flow spread uniformly throughout the lung. The lungs use the process hypoxic pulmonary vasoconstriction (HPV) to match blood to air, thereby optimizing gas exchange. Vessels that supply areas that receive little air constrict in order to minimize flow to poorly aerated lung regions. This process is critically important in the healthy lung; however Cystic Fibrosis and chronic obstructive pulmonary disease result in lungs that are globally oxygen starved.

In disease, low oxygen in the lung leads to blood vessel constriction throughout. This process may be linked to pulmonary hypertension and heart failure; two devastating conditions resulting in shortness of breath and death. This research will examine how specific membrane proteins respond to low oxygen by causing blood vessel constriction. One protein - known as CFTR - is the dysfunctional component in patients with Cystic Fibrosis. It is believed that CFTR plays a critical role in the molecular basis of HPV by acting as a magnet to draw other proteins into one domain of the cell membrane where they work together to cause blood vessel constriction.

 

 

Dr. J.J. Graham
Dr. J. Weinstein
St. Michael’s Hospital

Renal denervation for resistant hypertension: renal mechanisms, efficacy and safety

“Resistant Hypertension” (RH) is used to describe hypertensive patients who are not treated to target despite ≥3 anti-hypertensives or those at target on ≥4 anti-hypertensives. The prevalence is increasing and is associated with a 3-fold rise in the risk of subsequent adverse events, including kidney disease.

Increased renal sympathetic activity is observed in patients with RH. Recently, catheter-based renal sympathetic denervation has been shown to be an effective therapy for RH patients. This has been rapidly adopted in many countries as a treatment for RH, however the rapid adoption has resulted in unanswered questions regarding mode of action.

This grant application will attempt to answer some of these unresolved issues. The objectives of this study are to evaluate the effects of renal denervation therapy for resistant hypertension on the kidneys’ ability to handle sodium excretion; to assess the efficacy and safety of this therapy using MRI (renal MRI to assess safety, cardiac MRI to assess efficacy); and to ascertain whether any observed effects of this therapy are – at a cellular level - due to changes in expression of regulatory proteins. As a result of our study, a better understanding of the pathophysiological mode of action of this novel therapy is expected.

 

 

Dr. J. Harrold
Dr. R. Zemek
University of Ottawa

Epidemiology, risk factors, and characterization of neonatal visits to Ontario emergency departments

Newborns present frequently to Emergency Departments (ED) for care. Despite the high rate of usage, there are no large population-based studies examining why an infant requires an ED visit during the neonatal period (first 28 days of life).

The objective of this study is to describe and characterize the utilization of EDs in Ontario by neonates, including descriptive epidemiology, risk factors, and reasons for the visits, as well as the frequency of health services utilization. It will be the first population-based exploration of the utilization of EDs by neonates in Ontario, and to our knowledge, in Canada.

A predictive model for ED visits in the neonatal period will be developed. Results from this study will guide the development of future grant applications to prospectively validate the predictive model and to trial interventions in the hospital and the community to decrease ED use by neonates.

 

 

Dr. S.A. Jamal
Dr. C. Lok
Women’s College Hospital

Exercise in CKD: a pilot study

Broken bones or fractures are common in men and women with kidney disease and can lead to sickness and death. A strong and consistent risk factor for fracture is poor muscle strength.

The purpose of this study is to determine if walking and strength training exercises done at home three times a week for 3 months in 15 patients can improve tests of muscle function compared to 15 patients not participating in a walking and strength training program.

If it is found that this exercise program works to improve tests of muscle function, a larger, longer study to determine will be completed to see if exercise can reduce fractures in men and women with kidney disease.

 

 

Dr. J.K. Jaswal
Dr. D.A. Palma
Western University

Evaluating a novel multidisciplinary approach to teaching in Radiation Oncology

The field of radiation oncology (RO) has undergone a paradigm shift over the past decade. The development of precision radiotherapy techniques, using computed tomography scans (also called CT scans or CAT scans) to target tumors and avoid normal tissues, demand a thorough understanding of human anatomy and radiology. Complex anatomic sites can present major challenges for learners and are not well addressed in many residency programs.

Described here is a unique curriculum for anatomy and radiology instruction using a multidisciplinary approach, and represents the implementation of national program that has been previously tested in a pilot study. Thirty post-graduate trainees from all across Canada will participate in a 3-day course created by a team of physicians and educators. Pre-tests and post-tests will be administered to assess baseline knowledge and accuracy of contouring. Separate questionnaires will be used to gather statistics on demographic information, learning styles and levels of satisfaction with different aspects of the course such as content and delivery. Comparison of pre-test and post-test data will be performed to assess improvements.

It is hypothesized that incorporating anatomy and radiology teaching into the postgraduate RO curriculum is a beneficial educational intervention that will result in measurable improvements in resident performance and will ultimately improve clinical outcomes for our patients.

 

 

Dr. S.R. Johnson
University Health Network

Improving the validity of treatment effect estimates from observational data of uncommon diseases. The scleroderma lung transplant survival model

Scleroderma (Systemic Sclerosis (SSc)) is a disease that can affect the skin, joints, heart, lungs and kidneys. There is no cure. The leading cause of death for Canadians with SSc is end-stage lung disease from high pressure in the lungs called pulmonary arterial hypertension (PAH) or scarring of the lungs called interstitial lung disease (ILD). Lung transplant may be a cure for SSc lung disease, but it has potential risks (infection, death). Whether lung transplant improves survival is not known.

Using a novel research approach, this series of 3 studies will evaluate if lung transplant improves survival in SScPAH and SScILD. Part 1 will study experts’ beliefs about the benefits/risks of lung transplant for people with SSc, and will study factors that determine access to lung transplant and factors that affect survival. Part 2 will study an internet-based method of getting experts’ knowledge about lung transplant and scleroderma survival. Part 3 will study if lung transplant improves survival by comparing the survival of SScPAH and SScILD with other PAH and ILD patients.

This research will be the largest to study if lung transplant improves survival in this deadly disease, and will develop innovative research methods for researchers who study rare diseases.

 

 

Dr. C. Lee
Dr. P. Moayyedi
McMaster University

A prospective randomized double-blind trial of fresh versus frozen-and-thawed human biotherapy for recurrent Clostridium difficile infection

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea in developed countries and the rates of infection continue to rise. Treatment of a primary episode of CDI with metronidazole, or with oral vancomycin in severe cases, is the standard of care, with effectiveness of approximately 85%. Recurrence rates following treatment with metronidazole and vancomycin are approximately 20%, and increase to 40% following the first recurrence and to more than 60% after two or more recurrences.

Fecal transplantation, also known as human biotherapy (HBT), uses stool from a healthy screened donor to restore the healthy bacteria (flora) in the colon, and breaks the cycle of reintroducing antibiotics which prevent reestablishment of beneficial flora in the colon. A number of reports, and extensive experience, indicate that the cure rate of recurrent C. difficile is approximately 90% following HBT. However, HBT is not widely available in Canada, and use of fresh feces for HBT greatly limits the ability to standardize the delivery of healthy bacteria in different clinical settings. A recently published study supports the use of frozen HBT for the management of recurrent CDI, which could dramatically increase the feasibility of offering widespread HBT in Ontario. The feasibility of using frozen HBT offers a number of advantages such as immediate availability, as it can take up to 2 weeks to obtain donor screening laboratory results and the ability to provide consistent treatment across academic and community healthcare centres.

The purpose of this proposed investigation is to conduct a randomized double-blind trial of fresh versus frozen-and-thawed human biotherapy for recurrent Clostridium difficile infection. The primary objective is to determine the efficacy of frozen-and-thawed HBT compared to the fresh HBT.

 

 

Dr. D.M. Liu
Dr. V. Belostotsky
McMaster University

Fibroblast growth factor-23 (FGF-23) and renal function in children with chronic kidney disease

This study aims to explore the development of bone disease in children with chronic kidney disease (CKD). As the kidneys become damaged in chronic kidney disease, changes in levels of vitamin D, calcium, phosphate, and other hormones involved in healthy bone development arise. Fibroblast growth factor-23 (FGF-23) is a hormone that helps the body get rid of excess phosphate. In CKD, FGF-23 levels increase as the disease progresses and as more kidney filters are damaged; however the level of severity of kidney damage at which FGF-23 levels begin to rise is not known.

There have been very few studies that examine FGF-23 in children. This study would examine FGF-23 levels with other routine blood tests, including a marker called cystatin C that can measure kidney function in children between the ages of 18 months and 17 years of age at McMaster Children’s Hospital. Children’s Hospital, London Health Sciences Centre in London, ON will also be involved in this study.

 

 

Dr. K. McIntosh
Dr. W. Paterson
Queen’s University

Is non-cardiac chest pain caused by sustained longitudinal smooth muscle contraction?

Non-cardiac chest pain (NCCP) is a common disorder whose etiology is poorly understood. Some evidence suggests it may be related to sustained esophageal contractions (SECs) of the longitudinal smooth muscle in the esophagus. Previous studies have shown that acid is a trigger for SECs and results in shortening of the esophagus.

This study will evaluate whether patients with NCCP have an exaggerated esophageal shortening response to acid and whether that correlates with symptom production. To test this hypothesis, high-resolution esophageal manometry (HREM) will be used to measure esophageal shortening responses to acid in NCCP patients versus healthy controls. HREM provides an ideal way to measure esophageal shortening, as it shows real time migration of the lower esophageal sphincter.

If the hypothesis proves true, this will provide further insight into the mechanism of NCCP as well as providing a potential therapeutic target in the treatment of these patients.

 

 

Dr. J. Warman Chardon
Dr. K. Boycott
University of Ottawa

Evaluating exome sequencing for the diagnosis of limb girdle muscular dystrophy

Limb girdle muscular dystrophy (LGMD) describes a heterogeneous group of inherited muscle disorders characterized by progressive weakness and physical disability due to ongoing muscle degeneration. This muscle damage is caused by abnormal function of one of at least two dozen genes with many more remaining to be discovered.

Current clinical and molecular testing is often labour intensive, prohibitively expensive and does not identify new genes causing LGMD. A new technology, next-generation sequencing (NGS), can assess thousands of genes simultaneously and may be a more effective and faster genetic test for rare inherited disorders, such as LGMD, at a fraction of the cost compared to current testing. Analysis of protein coding genes by NGS (called “exome sequencing”), can rapidly interrogate known genes as well as identify new genes causing LGMD.

The objective of this study is to A) establish the clinical utility of exome sequencing for the diagnosis of LGMD patients and families living in Ontario and B) assess the cost effectiveness of exome sequencing compared with traditional genetic testing. It is predicted that exome sequencing will facilitate accurate, efficient and timely diagnoses, thereby avoiding unnecessary and expensive investigations, and facilitate pre-symptomatic management of complications and accurate genetic counseling for patients with LGMD.

 

 

Dr. E. Watts
Dr. E.H. Schemitsch
St. Michael’s Hospital

Endothelial progenitor cells for the biological augmentation of rotator cuff repair

Rotator cuff tears of the shoulder remain an unsolved problem in orthopaedics, and represent a substantial clinical burden. Impaired blood flow (vascularity) at the desired site of tendon-bone healing, as in rotator cuff tears, is a well-documented problem. Recent investigation of endothelial progenitor cells (EPCs) in fracture healing has demonstrated that EPC therapy significantly enhances both fracture healing and angiogenesis (blood vessel growth) in numerous animal models.

Given this documented capacity of EPC therapy, it stands to reason that the application of EPCs to a desired site of tendon-bone healing may improve the healing response. The proposed study seeks to address this by investigating the use of EPCs in a rotator cuff repair model. At the time of repair, specimens will be randomized to either receive EPC therapy or simply be surgically repaired.

The hypothesis of this study is that the application of EPC therapy will result in superior tendon-bone healing and strength. The development of a successful biological strategy for the improved healing of rotator cuff tears may result in improved outcomes and function for the many patients that suffer rotator cuff tears.






April 1 to June 30, 2013

 

 

Dr. M.H. Chui
Dr. B.A. Clarke
University Health Network

Genomic analysis of uterine leiomyosarcomas

Uterine leiomyosarcoma is a rare and aggressive cancer with poor survival rates. Understanding the biology of this disease is crucial for guiding selection of drugs for investigation in clinical trials and tailoring treatment to individual patients.

To realize this goal, we have compiled a comprehensive database of all patients with uterine leiomyosarcoma treated at the Princess Margaret Hospital, University Health Network from 1990 to 2012, annotated with tumor and patient characteristics, including survival data. This collection includes pathology and clinical outcome data and tumour tissue for identifying potential drug targets.

Recent advances in genomic sequencing technology have enabled comprehensive analysis of the genetic abnormalities in human cancer. In comparison to other gynecologic malignancies, the molecular genetic changes of ULMS that account for its malignant behaviour are virtually unknown. Thus, the purpose of this study is to elucidate the molecular genetic characteristics of uterine leiomyosarcoma by cataloguing the genetic alterations detected by whole genome analysis, with emphasis on identifying the aberrant molecular pathways that may be targetable for therapeutic intervention.

 

 

Dr. J.C. Hakim
Dr. N. Fleming
University of Ottawa

Health advocacy training in postgraduate obstetrics and gynecology: evaluation of a new curriculum through OSCE’s

The Royal College of Physicians and Surgeons of Canada (RCPSC) has mandated that the CanMEDS role of Health Advocate be addressed during postgraduate training. The University of Ottawa is the only training program in Ob/Gyn to have established a formal Health Advocacy curriculum for its residents. It is hypothesized that our Health Advocacy Curriculum has adequately exposed residents to the role of the Health Advocate, and that this can be evaluated through two Objective Structured Clinical Exam (OSCE) stations.

All residents in Ob/Gyn will be evaluated on a Health Advocacy station in a Fall 2013 OSCE exam. Residents will then complete the Health Advocacy Curriculum didactic teaching lectures held in January 2014 (intervention). These same residents will complete the Spring 2014 OSCE station on Health Advocacy. We will then evaluate and compare their two OSCE scores (pre and post intervention).

In this study, residents’ understanding of the concepts in Health Advocacy will be evaluated, as well as their ability to apply those concepts to a clinical scenario. The results will allow us not only to evaluate residents’ comprehension and competency in this role, but also provide a greater understanding of how this non-medical expert role should be taught and evaluated at the post-graduate level.

 

 

Dr. E. Leclair
Dr. N. Fleming
University of Ottawa

Factors which impact breastfeeding in adolescent pregnancies: a cohort study

Adolescent pregnancies are known to have a lower breastfeeding rate. To date, there are no large Canadian cohort studies reviewing breastfeeding in adolescent pregnancies. The largest published Canadian study involves 463 patients. In addition, in 2008, Mossman et al. reviewed the Manitoban adolescent’s attitude and confidence toward breastfeeding; however there are no studies available in
Ontario specifically looking at breastfeeding in adolescent pregnancies.

This study will determine the socio-demographic variables and health components which affect initiation of breastfeeding in Ontario’s adolescent mothers. With this knowledge, we will be able to assess the need and strategize possible breastfeeding program and support for adolescent mothers in order to improve breastfeeding initiation and possibly continuation rates. It is hypothesized that adolescents have a low levels of awareness about breastfeeding and its benefits as well as a poor initiation of breastfeeding due in part by knowledge, but also due to multiple sociodemographic characteristics found most often in adolescent pregnancies.

The ultimate objective of this study is to determine how breastfeeding initiation and continuation rates in Ontario adolescent mothers can be improved. The objective of this cohort study is to characterize the association between multiple demographic characteristic of pregnant adolescents with initiation and continuation of breastfeeding.

 

 

Dr. A.M. Morris
Mount Sinai Hospital

Evaluation of a province wide roll-out of antimicrobial stewardship programs in critical care units: a prospective, stepped-wedge observational study

Antimicrobial stewardship is a multi-disciplinary programmatic initiative aimed at optimizing antimicrobial therapy. The Mount Sinai Hospital-University Health Network Antimicrobial Stewardship Program (MSH-UHN ASP) is spearheading the implementation of ASPs in the ICUs of 14 academic institutions across Ontario.

The objective of this grant is to carry out a multi-faceted evaluation of ASPs in ICUs, focusing on multiple aspects. Quantitative outcomes will include: antimicrobial use, antimicrobial resistance amongst key bacterial isolates, antimicrobial associated hospital-acquired infections, ICU mortality and length of stay. Qualitative outcomes will include the use of surveys, interviews and focus groups with ICU clinicians (physicians, nurses and pharmacists), as well as ASP team members (ID physicians and pharmacists) to inquire about ASP knowledge, attitudes, perceptions, satisfaction, and areas for improvement. Economic analysis will utilize data from the Ontario Case Costing Initiative (OCCI). This will include an evaluation of the effects of ASPs on infectious disease practice, including costs associated with various therapeutic and diagnostic interventions.

This study hopes to demonstrate an intervention that will reduce bacterial resistance, nosocomial infections, and costs in the ICU, and to establish a model for ASPs that can be applied across Canada, as well as benchmarks for antimicrobial stewardship that will guide the care of infections in Canadian ICUs.

 

 

Dr. J. Neary
McMaster University

Colchicine for prevention of perioperative atrial fibrillation in patients undergoing thoracic surgery (COP-AF) pilot trial

Patients undergoing surgery are at risk of complications. Atrial fibrillation (a fast chaotic heart beat) is one of the most common complications occurring after chest (thoracic) surgery. Patients who develop atrial fibrillation after surgery have worse outcomes, which include: death, stroke, and prolonged stays in the intensive care unit and in the hospital. Atrial fibrillation occurs due to excessive inflammation that occurs after surgery. Previous studies reported that regulating this inflammation results in less atrial fibrillation.

Research suggests that colchicine, an anti-inflammatory drug, may be effective in preventing atrial fibrillation after surgery. A pilot trial will be conducted to determine the feasibility of doing a large-trial to test whether colchicine can prevent atrial fibrillation after surgery. The study will be conducted in two major hospitals in Canada; St. Joseph Hospital in Hamilton, ON and University of Manitoba Health Sciences Centre, Winnipeg, MB. The Population Health Research Institute in Hamilton will be the coordinating site. Patients will receive colchicine or placebo for 10 days after the surgery and will be monitored while in-hospital to see if they develop atrial fibrillation.

 

 

Dr. S. Petis
Dr. E. Vasarhelyi
Western University

A randomized trial comparing the direct lateral, anterior, and posterior approach: Imaging and clinical outcomes in total hip arthroplasty

Total hip arthroplasty (THA) is a reliable surgery for severe arthritis of the hip joint. It is a common surgical procedure in Canada, with over 13,000 THAs being performed each year. Surgical approach is a decision that may have a profound impact on patient outcomes. Currently, the direct lateral and posterior approaches to the hip are the most common approaches used in Canada; however the anterior approach is gaining popularity due to its hypothetical muscle sparing properties and shorter hospital stays.

There is a paucity of literature to support these claims. Thirty patients will be randomized to receive a THA using either an anterior, posterior, or lateral approach to the hip. Pre‐ and post‐operative clinical assessments and outcome measures will be completed. Each participant will receive a MRI of the involved hip at 24‐weeks post‐operatively. The images will be reviewed to determine soft tissue damage inherent in each approach. These findings will be correlated with the clinical assessments.

This study will determine the degree of soft tissue pathology using each surgical approach. This data will help surgeons educate their patients regarding the risks of surgery. It will also help guide patient rehabilitation to improve patient outcomes and shorten hospital stays.

 

 

Dr. J. Phillips
Dr. J. Drake
Hospital for Sick Children

Mathematical optimization of pediatric cranial vault remodeling and robotic CO2 etching of skull contours

This study aims to use mathematical methods to determine a priori the optimal number of bone cuts and the location of discrete bone pieces in the cranial vault remodeling procedure, based on an average normative three-dimensional (3D) skull shape previously generated from actual subject computed tomography (CT) image data.

The methodology involves assigning a fixed number of surgically viable cuts to a discrete set of locations on the fronto-orbital bandeau surface that will minimize the area difference between the post-operative and ideal normative skulls. The clinical application of the algorithm will be validated, by quantifying both the residual deformity on routine post-operative CT scans and surgery “costs” including length of surgery. Additionally, a robotic technique will be implemented, whereby a 3D laser scanning system will register 3D artificial skulls of prospective patients to the corresponding virtual models. A robotic arm will subsequently etch the outlines of the pre-determined cut locations on the fabricated skull models, which will then be reconstructed and their residual deformity quantified.

This combined system has the potential to ensure an optimal fitting of the bone pieces covering the cranial surface; minimize variability of results; increase objectivity and accuracy in the surgical procedure; and reduce operation time.

 

 

Dr. K. Schwartz
Dr. U. Allen
Hospital for Sick Children

Immunogenicity and safety of human papilloma virus vaccine in solid organ transplant recipients

The human papilloma virus (HPV) is known to be an important cause of cervical and anal cancers. Studies on patients who have received a solid organ transplant (such as a liver or kidney transplant) have suggested the risk of HPV-related cancers may be higher in this population. The HPV vaccine, Gardasil®, has been approved for use in males and females by Health Canada. In studies on healthy subjects this vaccine is nearly 100% effective at preventing infections from HPV serotypes that are in the vaccine. These serotypes, representing different viral strains, are known to cause 70% of cervical cancers and 90% of genital warts. The vaccine was also shown to be very safe and well tolerated in healthy subjects.

Transplant patients are at higher risk of HPV related complications and cancers. As a result transplant experts have recommended this vaccine for use in their patients; however there have been no studies looking at the response to vaccination or safety of this vaccine in solid organ transplant recipients. The objective of this research is to study the immune response and side effects of Gardasil® in children who have received kidney or liver transplants. Immune responses to the vaccine in healthy adolescent females will be compared to female liver and kidney transplant recipients. 12-19 year old females will be recruited, as the province of Ontario funds the vaccine for this group. The transplant subjects will be evaluated for side effects after they receive the vaccine.

 

 

Dr. S.K.P. Shivananda
McMaster University

Care bundle to improve oxygenation in newborns (CBION)

It is very difficult to maintain the oxygen levels of preterm babies within a safe range in neonatal intensive care units (NICU). Babies’ breathing can stop temporarily and their heart rate and oxygen levels can drop to unsafe levels. When this happens frequently, potentially blinding eye disease, chronic lung disease and death can result. Apart from under-developed organs, human factors like variation in caregiver practices, lack of useful oxygen monitoring tool, and very little research in this area contribute to this problem.

To date, the ideal oxygen range for preterm babies has not been well defined. New evidence is helping to clarify this and supports the use of technology in monitoring oxygen levels. Several practices are now known to be effective in maintaining safe oxygen levels but adopting these practices in NICUs can be challenging. This study will look at whether caregivers’ use of evidence-based practices and new oxygen monitoring technology helps to maintain safe oxygen levels. Tailored training using simulation and coaching support will be used to help NICU caregivers learn and apply the new practices.

It is believed that using these new practices effectively will lead to better oxygen control in preterm babies and therefore lower rates of complications.

 

 

Dr. M.C. Sklar
Dr. D.P. Goldstein
Princess Margaret Hospital

Does frailty predict outcomes in elderly patients undergoing major head neck oncologic surgery?

The Canadian elderly population is the fastest growing age demographic. As the population continues to age, the number of elderly individuals diagnosed with a malignant neoplasm of the head and neck rises as well. Head and neck surgeons are now faced with an ever increasingly difficult task of maximizing benefits and minimizing harms in this challenging patient population. Head and neck cancer surgeries are often long (between 4 to 12hrs) with a frequent need for tracheotomy and feeding tubes and are often associated with long-term disruption of shoulder function, speech, swallowing and cosmesis. Head and neck cancer patients are also frequently malnourished, have a history of alcoholism and multiple comorbidities.

To help determine which elderly patients are best fit for major head and neck surgery, we will use the concept of frailty, which is defined as the decreased physiologic reserve across multiple organ systems to assess these elderly patients. A previously developed Frailty assessment tool, the Frailty Index, will be administered to eligible patients > 65 years of age prior to undergoing major head and neck surgery. Patients will be followed through their hospital admission with complications, length of stay and level of care needed on discharge being recorded.






January 1 to March 31, 2013

In the first quarter of 2013, the Foundation approved grants for the following projects:

 

 

Dr. C.L. Atzema
Sunnybrook Health Sciences Centre

Follow-up care after a visit to the Emergency Department: assessing the frequency and timeliness in patients with chronic disease exacerbations

Each year 12 million people visit an emergency department (ED) in Canada, with the highest rates among older persons. Some will be admitted to hospital, but most are discharged home. There are some patients for whom both options are possible. Discharge avoids the high cost of a hospitalization, risk of a hospital-acquired infection, and delirium and permanent decline in the elderly. However, to safely discharge these patients, a prompt follow-up appointment with the family physician (FP) must be ensured. Because the availability of follow-up care is often uncertain, many patients are simply admitted to hospital.

With the aging of the population, ED visits are going to accelerate. Using Ontario databases, this study will identify Ontarians seen in an Ontario ED with 3 common chronic diseases. This research will see how many of those patients saw a doctor after the ED visit and determine whether lack of follow-up was associated with more deaths, return ED visits, and taking recommended medications.

The study will provide the first scientific evidence as to whether the current system of care between the ED and FP is adequate, and allow us to make informed decisions regarding a future intervention study.

 

 

Dr. B. Bielawska
Dr. L.C. Hookey
Queen’s University

Endoscopist factors and risk of perforation in adult colonoscopy: an Ontario population-based study

Bowel perforation is a serious and sometimes fatal complication of colonoscopy. Many patient factors are associated with higher perforation rates but despite decades of experience with colonoscopy, little is known about endoscopist and procedural factors that can affect perforation risk. It has been speculated that there is increased perforation risk with propofol sedation in colonoscopy, as well as when procedures are performed by less experienced and non-gastroenterologist endoscopists.

The influence of endoscopist factors on colonoscopic perforation risk was recently investigated in a large American database and found increased risk of perforation in procedures involving trainees and non-gastroenterologist endoscopists. This study will investigate the effect of propofol sedation as well as endoscopist specialty, training and experience on perforation risk in colonoscopy in Ontario using information from existing health databases.

These are critical issues to examine given the current climate that sees propofol rapidly emerging as a preferred mode of sedation in colonoscopy and growing pressures to recruit more non-gastroenterologist endoscopists to meet rising demand needs for procedures.

 

 

Dr. L.R. Brandao
Hospital for Sick Children

Fluid accumulation in pediatric post-thrombotic syndrome

Post-thrombotic syndrome (PTS) is a chronic, costly, and potentially devastating complication of acute deep vein thrombosis, now recognized as very prevalent in children. The two pediatric instruments available to assess PTS have acknowledged limitations and need improvement.

Limb edema is the most common and earliest clinical finding of PTS. The pediatric instruments use different items measured by different techniques to determine the presence of edema. The hypothesis of this study is that their diagnostic ability is suboptimal. This research includes measuring the discriminative ability of different techniques to detect fluid accumulation in children at risk for PTS, comparing their results with a reference test [bioimpedance analysis (BIA)]. It is aimed to determine which technique, item, or combination of items better predict the presence of edema. Because this is a novel application of BIA, BIA ranges in healthy children will also be established.

The potential unwanted consequences of suboptimal measurement of edema include overcalling the frequency and severity of PTS. As the use of upfront aggressive therapies to prevent PTS in children increases, so does the need of having valid and reliable PTS instruments. A better discrimination of the presence or absence of edema is an important step towards improving diagnostic instruments of pediatric PTS.

 

 

Dr. D. Cook
McMaster University

Probiotics: prevention of severe pneumonia and endotracheal colonization trial (PROSPECT): a feasibility clinical trial

Probiotics are commercially available live bacteria thought to have health benefits when ingested. Studies have shown that probiotics may prevent 25% of all pneumonias that develop when on a mechanical ventilator, known as ventilator associated pneumonia (VAP); however, these studies have been small and potentially biased. Therefore, whether probiotics are truly helpful in preventing VAP remains unclear.

A randomized controlled trial will be performed in critically ill ventilated patients in 4 ICUs in Ontario, investigating whether L. rhamnosus GG (LGG, a common probiotic) prevents VAP. The overall goal is to test the feasibility of doing a larger trial. The primary goal of the pilot is to ensure that we can successfully enroll patients; have high protocol adherence, and that patients receive the correct intervention. How LGG affects harmful bacteria in the stool, and the body’s response to infection will also be evaluated. 60 adults admitted to ICU who need the breathing machine will be enrolled. Patients will receive either LGG or a placebo, twice daily given down a feeding tube into the stomach until 24 hours after they are breathing on their own.

This trial is important in the ongoing search for more effective VAP prevention strategies. Knowledge from this pilot trial will ensure that the larger trial is well done and efficient.

 

 

Dr. J. Frei
Dr. L. Giglia
McMaster University

Troponin T levels as a marker for cardiac ischemia associated with in utero cocaine exposure

The rate of crack cocaine use in Canada is rising. Newborns who were exposed to cocaine prenatally can have significant cardiac side effects including ischemia, impaired cardiac output, arrhythmias and congenital heart defects. However, there are currently no guidelines concerning screening for at risk infants. While ECG has been used to identify ischemia in these infants, data from newborns with perinatal asphyxia suggests that cardiac Troponin T (cTnT) may be better at identifying myocardial ischemia. Therefore, previous studies using ECG in newborns prenatally exposed to cocaine may have underestimated the rate of myocardial ischemia. This is important to make decisions about screening for early diagnosis, treatment and long-term monitoring.

To study the usefulness of cardiac cTnT in evaluating myocardial ischemia in newborns with prenatal cocaine exposure, forty-six infants with prenatal cocaine exposure and 46 gestational age-matched controls will be prospectively enrolled at St. Joseph’s Hospital in Hamilton. Cocaine exposure status will be determined through maternal report, and confirmed using urine toxicology. Each participant will have myocardial ischemia evaluated by cTnT levels and ECGs at 24-28 hours of life. Multivariate analyses, controlling for potential confounders, will be used to assess for differences in frequency of myocardial ischemia between groups.

 

 

Dr. A. Gangji
McMaster University

BIOVISION: Does bio-impedance analysis predict volume overload states and clinically relevant outcomes in septic intensive care unit patients? A prospective observational study

Patients with severe infections require large volumes of fluid to stabilize blood pressure during initial resuscitation. Once blood pressure has been stabilized, extra fluid can accumulate which can lead to increased time spent on the ventilator, development of kidney failure, and longer stay in the Intensive Care Unit (ICU).

Clinicians often have difficulty in determining if a patient is retaining too much fluid. The current standard for determining how much fluid a patient has is by clinical examination or by measurement with a catheter placed in a large central vein. Both of these techniques are inaccurate and the catheter technique is invasive. Alternatively, Bioelectric Impedance Analysis (BIA) is a safe, non-invasive test that has been shown to predict the amount of fluid present in one’s body by measuring the electrical properties.

In this study, BIA measurements will be taken daily during the patients’ ICU stay. The researchers aim to determine: 1) the relationship between BIA measurements and other measures of volume, and 2) the relationship between BIA measurements and important clinical outcomes related to fluid overload such as time on the ventilator. If BIA can predict volume, then a subsequent trial will be designed to evaluate a BIA-guided fluid management strategy.

 

 

Dr. E.C. Goligher
Dr. N.D. Ferguson
University Health Network

Diaphragm monitoring techniques for muscle-protective mechanical ventilation: evaluating validity, reliability and feasibility

Mechanical ventilation is a life-saving intervention for people with acute respiratory failure. However, doctors have recently discovered that the ventilator weakens the diaphragm significantly. Because a strong diaphragm enables patients to begin breathing without assistance from the ventilator, diaphragm weakness keeps patients dependent on the ventilator. As a result, their stay in the intensive care unit is longer and they are experience more complications related to being on a ventilator.

Changing current methods of mechanical ventilation might prevent diaphragm weakness and speed up recovery. To design and test improved ventilation strategies, reliable methods for measuring diaphragm activity and strength are required. This research proposal is to develop new diaphragm monitoring techniques, providing a vitally important foundation for future efforts to improve mechanical ventilation to maximize recovery from acute respiratory failure.

 

 

Dr. A.F. Huang
Dr. H. Clarke
University Health Network

Reducing the incidence and severity of post-thoracotomy pain syndrome: a randomized, double blind, study comparing a novel intracostal closure technique to the classical pericostal suture closure technique

Post-thoracotomy pain syndrome (PTPS) is defined as pain that recurs or persists along a thoracotomy scar at least 2 months following surgery and presents a frustrating challenge to patient and healthcare providers alike. While not fully understood, PTPS can affect up to 60% of patients undergoing thoracotomies, and results in significant functional and psychological impairment. Classically, incisions are closed using pericostal sutures that run under the inferior rib of the thoracotomy. A proposed mechanism for PTPS involves impingement of the intercostal nerves during closure.

Closure of thoracotomies using intracostal sutures is a novel technique whereby sutures are passed through holes drilled into the inferior rib, avoiding compression of neurovascular structures. There is a scarcity of literature available on the effect of intracostal suture closure on PTPS; therefore, a double-blind, randomized control study is proposed, involving 90 patients undergoing elective posterolateral thoracotomies. Participants will be randomly assigned to undergo thoracotomy closure with pericostal sutures or intracostal sutures.

The primary outcome will assess the incidence and severity of PTPS at 3 months after surgery between groups. Secondary outcomes will assess acute postoperative pain scores and opioid consumption for the first 48 hours after surgery, time to ambulation, hospital stay, sleep disturbance, and psychological factors which predispose patients to develop PTPS.

 

 

Dr. J. Maguire
Dr. M. Walker
St. Michael’s Hospital

Determinants of late preterm birth

Late preterm birth (34-37 weeks) is increasingly common in Canada. While outcomes were once thought to be the same as term infants, it is now recognized that they are at increased risk of many newborn health problems including breathing difficulties, feeding problems, low blood sugar, lengthy hospitalization and even death. Longer term effects including behavioral issues, school difficulties, and obesity have also been reported.

Using a provincial database that registers nearly all births in Ontario (BORN Ontario), the goal of this study is to determine risk factors for late preterm birth which could be targets for interventions to reduce late preterm birth. To do this, several analytic approaches will be used. First, regression techniques will be used to determine which risk factors are independently associated with late preterm birth. Second, novel time series methods will be used to identify changes in trends of risk factors which correlate with changes in trends of late preterm birth. Finally, the extent to which modifying these risk factors might reduce the rate of late preterm birth will be identified.

Through a better understanding of the risk factors for late preterm birth, strategies can be developed to prevent late preterm birth, and reduce suffering and the increasing burden placed on our health care system.

 

 

Dr. M.D. McKee
Dr. E.H. Schemitsch
St. Michael’s Hospital

Operative versus non-operative treatment of acute unstable chest wall injuries: a multi centered randomized controlled trial

The proposed study is a multi-center, prospective, randomized controlled trial comparing surgical treatment of carefully selected, acute, unstable chest wall injuries with the current gold standard of non-operative management. The aim is to determine if surgical fixation of unstable chest injuries decreases the number of days spent on mechanical ventilation compared to non-operative treatment of these injuries.

Eight-four patients with eligible rib fractures will be randomized into two groups: non-operative (mechanical ventilation, suctioning of ET tube, chest physiotherapy, elevation of the head of the bed to 30° and pain control) or operative (same non-operative treatment as mentioned above, in addition to operative fixation of the unstable chest consisting of reduction and stabilization of the rib fractures by use of plates and screws). Patients will be seen daily until discharged from the ICU and will be followed up at 1, 2, 6 weeks and 3, 6, 12 months post injury. Unstable chest wall injury fixation represents an ideal opportunity to dramatically improve the short and long-term outcome of polytrauma patients. There is popular support for this approach in the non-orthopaedic literature: additionally, in a recent poll, 66% of orthopaedic surgeons favored fixation of selected rib fractures. There is a need to perform a definitive study in this area, which has the potential to change the current standard of care for these injuries.

 

 

Dr. L.E. Reid
Dr. N. Dudek
University of Ottawa

Going places: does the two-minute walk test predict the six-minute walk test in lower extremity amputees?

Community mobility is a primary rehabilitation goal for people with lower limb amputations. Clinicians need to efficiently measure potential for walking in the community. Lower extremity amputees walk an average of 69 meters (m) in the two-minute walk test (2MWT). This is far below the 300m required to function in the community. In the 6MWT, patients may walk 300m, but this test has not been fully validated for the amputee population. As well, it takes more therapy time to complete.

This study will first further validate the 6MWT in the lower extremity amputee population. The second component will determine whether 2MWT results predict 6MWT performance. Participants from The Ottawa Hospital Rehabilitation Centre outpatient amputee clinic will complete the 2MWT, 6MWT, Timed Up and Go test, Locomotor Capability Index, Houghton scale and Activities-specific Balance Confidence scale. Results will be analysed to further assess whether the 6MWT is a valid measure of community mobility distances. Further analysis will examine the extent to which the 2MWT predicts 6MWT performance.

If the 2MWT predicts 6MWT results, the two-minute test can be used instead of the six-minute test to examine community mobility potential, decreasing patient burden and saving valuable therapy time.

 

 

Dr. K. Sabri
McMaster University

Pediatric eye disease video interpretation and diagnosis (PED-VID) study

Telemedicine is defined as the delivery of clinical health care services and the exchange of health information across large distances using communication technologies such as videos, images or patient interviews. In doing so, telemedicine provides essential and timely care to individuals who live in rural or isolated communities. Since examination of the eyes alone is often enough to make a diagnosis and recommend a treatment plan for eye disease, Ophthalmology is well-suited to the use of telemedicine.

The purpose of this study is to determine whether telemedicine using videography can be used as a tool for interpreting pediatric eye examinations, diagnosing amblyogenic eye disease (preventable vision loss or “lazy eye”) in children and identifying children with potential emergencies such as tumours or infections within the brain.

To answer this question, this study will assess whether interpreting the video recording of a child’s eye examination can be as reliable as direct patient examination for diagnosing eye disease. This innovative tool has the potential to improve access to health care for many children living in rural or remote parts of Ontario and beyond.

 

 

Dr. L.E. Tile
Dr. A.M.W. Cheung
University Health Network

Effect of teriparatide in fracture healing in patients with incomplete atypical femur fractures: a randomized controlled trial (The TAFF Trial)

Atypical femur (thigh bone) fractures (AFFs) are uncommon low-trauma fractures which often occur without warning, are highly debilitating, and are slow to heal. As physicians learn more about them, AFFs are increasingly being identified prior to a total break. However, there is no evidence on the best way to treat these non-displaced AFFs. One option is teriparatide, an osteoporosis medication that can build new bone.

This study proposes to conduct a double blind randomized placebo controlled trial to examine whether teriparatide use in AFF patients with an incomplete break will help accelerate fracture healing and prevent surgical intervention. 60 women and men over the age of 30 who have experienced an incomplete AFF will be recruited. Participants will be randomly assigned to either teriparatide (20 mcg/day) or placebo (using an identical injection pen) for up to 2 years.

The co-primary outcomes are:
(1) a measure of functional ability (modified WOMAC) from baseline to 12 months;
(2) the proportion of patients requiring surgical intervention from baseline to 12 months.

Secondary outcomes include change in pain levels and fracture healing on x-ray/CT scans at 12 months. As AFFs are highly debilitating, a trial examining the use of Teriparatide in this population is urgently needed.

 

 

Dr. P.D. Violette
Dr. H. Razni
Western University

A randomized controlled trial assessing the efficacy of antimicrobial prophylaxis for extracorporeal shock wave lithotripsy on reducing urinary tract infection

The lifetime risk of developing a kidney stone is estimated between 1 and 15%. One of the most common therapies for kidney stones is extracorporeal shock wave lithotripsy (SWL). This procedure is favored because it has few complications; however urine infections are among the most common. Because of this risk the American Urological Association recommends pre-SWL antibiotics for all patients. However, this approach is controversial because studies to date are of poor quality and there is concern over antibiotic resistance. Therefore the European Association of Urology recommends only selective use of antibiotics pre-SWL.

To resolve this conflict and establish the most appropriate strategy for Ontarians, this study proposes to perform a randomized trial comparing pre-procedure antibiotics to no antibiotics among patients who undergo SWL. This trial will recruit approximately 1300 patients half of which will receive pre-SWL antibiotics. The rates of urinary tract infection and symptoms at 7-10 days post-SWL will be compared and the effectiveness of pre-SWL antibiotics will be determined.

If the study shows a benefit then this will reduce the number of infections suffered by patients. If the study shows no benefit then the reduced use of antibiotics will provide a cost savings and reduce the risk of antibiotic resistance.