The Physicians’ Services Incorporated Foundation
This site is primarily for individuals with an interest in the research programs of the Foundation
|
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 December 2, 2009
The Foundation approved grants with a total
value of $1,118,500 in the second quarter of 2009, for the
following projects:
Dr. S. Abadi
Dr. N. Paul
Toronto General Hospital
Adult breast radiation dose from cardiothoracic imaging
protocols, a phantom study.
There is increasing concern regarding the sensitivity of breast
tissue irradiation from diagnostic cardiothoracic CT; therefore,
it is imperative to determine the accuracy of the DLP readout,
the lowest dose threshold for diagnostic scans, and to address
the effectiveness of different dose reduction strategies.
The objectives of this study are to determine the effective
radiation dose (EDE) to breast from cardiothoracic CT and to
assess the effectiveness of dose radiation strategies and their
impact on image quality (IQ).
Dr. T. Best
Northern Ontario School of Medicine
Surgical peripheral nerve decompression for the treatment of
diabetic neuropathy in the foot.
Diabetic neuropathy is a condition that develops in many persons
suffering from diabetes mellitus. This condition causes burning
pain and decreases feeling in the foot, and it is a major
contributor to the development of foot ulcers in the diabetic,
which not uncommonly lead to prolonged medical treatments and
amputations. It is, furthermore, a major cause of pain and
disability in diabetics, while also representing a large economic
burden to the health care system. Treatment options remain
limited and often ineffective.
In recent years, there have been several reports claiming an
effective surgical treatment for this condition. This surgery
consists of decompressing the major lower limb nerves, similar to
carpel tunnel release surgery in the hand. However, these reports
have been of low quality, and the treatment remains unproven.
The objective of this study is to test if this surgery is an
effective treatment for diabetic neuropathy of the foot. The
results of this study will help determine if this treatment is
effective for diabetic neuropathy in the foot; if positive, this
treatment will not only relieve much patient suffering, but will
also relieve the health care system of some of the current
financial burden of caring for patients with this condition. If
the study results are negative, health care resources will be
saved by discouraging surgeons from continuing to offer this
treatment.
Dr. T. Lindsay
Toronto General Hospital
Complement mediated organ injury following ruptured abdominal
aortic aneurysm: Human and animal investigations leading to pilot
intervention studies.
The abdominal aorta, the main abdominal blood vessel, can
silently enlarge forming an aneurysm. If repaired electively
excellent survival can be achieved with few complications. Those
aneurysms that rupture and present to the emergency room alive
have a 40% thirty day mortality rate. This is 10 fold higher that
the mortality associated with elective repair. Despite successful
surgical repair, many patients develop lung, kidney, and liver
failure for which the only therapy is supportive care and
contribute to the mortality.
Research performed in this investigator’s lab has
demonstrated that an intrinsic host defence mechanism, the
complement cascade, becomes activated and appears to contribute
to the development of organ dysfunction.
The novel human studies proposed in this grant are designed to
evaluate the role of complement activation and determine if it is
responsible for development of organ failure and mortality. The
animal experiments are designed to study aspects of organ injury
induced by complement and related pathways that can’t be
performed or evaluated in humans. The ultimate goal of these
investigations is to have sufficient data to implicate complement
activation in organ injury following aortic rupture that a pilot
study of complement inhibition in RAAA patients will become a
reality.
Dr. E. Pope
Hospital for SickChildren
Nadolol for proliferating infantile hemangiomas: A
prospective open label study.
Infantile hemangiomas (IH) are the most common tumors of infancy
affecting approximately 10% of Caucasian children. For IH
requiring systemic treatment (approximately 10%), steroids by
mouth comprise the main therapeutic option and may be associated
with significant side effects. In June 2008, the beta blocker,
propranolol, was reported to be beneficial in the treatment of
IH. Nadolol is a beta blocker which acts similarly as
propranolol, while offering several advantages.
To explore the efficacy and safety of nadolol in IH in this pilot
study, nadolol will be offered to 10 patients of IH in gradually
increasing doses with close monitoring for any side effects.
Primary outcome measure will consist of the proportion of
subjects with at least 75% improvement in the extent of the
hemangioma at 1 year of age as compared to baseline.
If nadolol is proven safe and efficacious, more children with IH
can be offered treatment; these children will not require laser
or surgical intervention to deal with the aftermath of IH, thus
reducing the health care costs.
Dr. A. Advani
St. Michael’s Hospital
Oral anti-VEGF therapy for advanced diabetic nephropathy,
alone and in combination with RAS-blockade.
Diabetes is reaching epidemic proportions in Canada and has
serious consequences for long-term health. Among these
consequences is kidney disease, which represents the most common
cause of kidney failure in Canada. Unfortunately, current
treatments to prevent diabetic kidney disease are only partly
effective, and new therapies are urgently needed.
A small protein called VEGF causes the tiny blood vessels of the
kidney to become leaky. While blocking the way VEGF protects the
kidney very soon after diabetes has developed, it is not known
whether the same approach may help people who have had diabetes
for many years.
These studies will investigate whether inhibiting VEGF can
prevent the development of kidney failure with diabetes, when
used alone and in combination with currently established
treatments. This investigator will use an experimental mouse
model of diabetic kidney disease that, after 6 months, develops
kidney failure very similar to that seen in patients. This
investigator will identify whether the VEGF inhibitor prevents
the development of kidney failure. These studies have the direct
potential to lead to new treatments to prevent or even reverse
the progression of kidney disease in diabetes.
Dr. C. dos Santos
St. Michael’s Hospital
Identification of cyclic-stretch sensitive transcription
factors in pulmonary epithelial cells that play a role in
ventilator induced lung injury (VILI).
Acute Respiratory Distress Syndrome (ARDS) is a devastating
problem in intensive care. This syndrome is characterized by
severe lung inflammation – for which patients need to be
placed on life support. Although mechanical ventilation can be
life saving, repeated lung stretch from artificial ventilation
itself is injurious - called ventilator induced lung injury
(VILI). VILI contributes to the morbidity and mortality of ARDS
patients, and other than reducing ventilator settings, there are
no treatments for it.
To identify novel molecules involved in “stretch”
injury, this investigator stretched lung cells in-vitro and
analyzed their response using microarray. When they compared
regulatory sequences present in the genes that responded to
stretch versus those that did not, this investigator found that
they shared a binding sequence for the transcription factor
– activating transcription factor 3 (ATF3).
In this study, the investigator proposes to demonstrate that ATF3
plays a role in vivo. For this purpose, they have obtained the
knock out mouse for this gene and plan to expose these mice to
VILI. Preliminary data suggests that ATF3-deficient animals are
much more susceptible to VILI than normal mice. Consequently, the
investigator proposes ATF3 protects from injury. Understanding
how protection occurs will enable development of novel treatments
for VILI.
Dr. A. Riganomti
St. Michael’s hospital
Effect of bilateral scalp nerve blocks on post-operative pain
and discharge times in patients undergoing supra-tentorial
craniotomy and general anaesthesia.
The objective of this study is to demonstrate that scalp nerve
blocks ("scalp freezing"), performed at the end brain
surgery, will reduce post-operative pain, opioids side effects
and the time required for post-anaesthesia care unit (PACU) and
hospital discharge.
Dr. C. Pound
University of Ottawa
The impact of a breastfeeding support intervention on
breastfeeding duration in jaundiced infants admitted to a
tertiary care centre hospital: A randomized controlled trial.
Breastfeeding decreases the risk of infectious illnesses in
infants, strengthens the mother-infant bond and decreases health
care costs by making infants healthier. There is evidence that
when infants with jaundice are hospitalized their mothers are at
risk of stopping breastfeeding.
This study’s main objective is to determine the effect of a
breastfeeding intervention on breastfeeding duration in jaundiced
infants. Mothers of infants in the intervention group will meet
with a lactation consultant on four occasions. Mothers of infants
in the control group will receive regular hospital care.
Follow-up of mothers will continue until the infant is 6 old.
Information will be collected on length of time that infants are
fed only breast milk, future visits to health care providers,
mothers’ perception of their physicians’ attitudes
towards breastfeeding, and mothers’ experiences at the
hospital, as well as feedback on the intervention.
The results of this study will clarify the importance of offering
breastfeeding support to mothers of these infants and help
determine whether there is a need for lactation specialists in
children’s hospitals. It will allow this investigator to
determine the impact of such interventions on children’s
health in their first 6 months of life, as well as collect
information on support offered to breastfeeding women by primary
care physicians.
Dr. J. Muscedere
Queen’s University
Candida in Respiratory Tract Secretions of Critically Ill
Patients and Efficacy of Treatment (The CANTREAT Study): A
prospective, randomized, double blind, placebo controlled pilot
study.
Pneumonia that arises in critically ill patients on a mechanical
ventilator is termed ventilator associated pneumonia (VAP). VAP
can be life threatening and is at times fatal. In spite of its
frequent occurrence in critically ill patients, optimal therapy
for VAP is not known. In this regard, during investigations for
the presence of VAP, Candida spp. or yeast are frequently grown
when the sputum from patients suspected of VAP is cultured. Until
recently, the presence of yeast was thought to be inconsequential
and not treated. However, research conducted by this investigator
has revealed that the presence of Candida spp. in the sputum is
associated with worsened outcomes (including prolonged ICU and
hospital length of stay and higher mortality). It is unknown if
Candida is responsible or is just associated with the worsened
outcomes.
The only way to determine this is to conduct a randomized
controlled treatment trial, and statistical analysis reveals that
this trial will need a trial of over 1000 patients to answer this
question. This investigator is planning to undertake this trial,
but first needs to conduct a pilot study to optimize study
procedures, ascertain the feasibility of conducting a large study
and to obtain further information that will be useful in a future
trial.
Dr. M. Kolla
Dr. J. Meyer
Centre for Addictions and Mental Health
An investigation of prefrontal monoamine oxidase-A density in
individuals with major depressive episode and comorbid borderline
personality disorder.
Clinical depression is the fourth leading cause of death and
disability, and a large portion of this burden is treatment
resistant depression. Treatment resistance to antidepressants
often occurs when comorbid psychiatric illness is present;
borderline personality disorder (BPD) is a common, disabling
illness that is often comorbid with clinical depression.
The proposed study will measure monoamine oxidase A (MAO-A)
levels during clinical depression with comorbid BPD. MAO-A is a
brain protein that destroys substances like serotonin. These
investigators have found that MAO-A levels are elevated in
clinical depression without comorbid illness. It is known that
production of MAO-A is increased during stress. Greater stress
responses occur in BPD. Therefore, these investigators
hypothesize that MAO-A will be higher in the brains of people
with clinical depression and comorbid BPD compared with people
with clinical depression and no comorbid psychiatric illness.
The objectives of this study are to compare brain MAO-A levels
during clinical depression with comorbid BPD versus clinical
depression without comorbid psychiatric illness, and to compare
brain MAO-A levels during clinical depression with comorbid BPD
versus healthy participants.
Dr. H. Amsalem
Dr. J. Kingdom
Mount Sinai Hospital
Decidual neutrophils a novel finding: Their role in second
trimester placentation.
The fetomaternal interface once thought to be an immune privilege
site is now known to harbor a large population of maternal immune
cells. These cells, specifically Natural Killer cells, play a
major role in both normal and aberrant uterine angiogenesis of
early pregnancy. Little is known about the role of Neutrophils in
placentation. Neutrophils, a major component of the immune
system, have been shown to express angiogenic properties in
tumours. Current literature indicates their absence from the
first trimester decidua.
Preliminary results from these investigators confirm this finding
and show for the first time a surprisingly large number of
neutrophils in the second trimester decidua. The aim of this
study is to confirm these novel results and to learn more about
the origin and role of these cells in normal and aberrant
placentation. Specifically, these investigators will perform FACS
analysis on decidual leukocytes to confirm the presence of
neutrophils and the specific receptor repertoire they express.
Immunostaining will be used to identify their distribution within
the tissue and investigate the specific signals recruiting them
to the decidua. Furthermore, these investigators will obtain
decidua from pathological pregnancies during caesarean section
(Preeclamptic and Intrauterine Growth restriction patients) and
attempt to correlate altered neutrophil number or function with
the clinical presentation.
Dr. S. Trop
Dr. S. verma
St. Michael’s hospital
Comparison of the inflammatory response to cardiopulmonary
bypass between South Asians and Caucasians.
The use of cardiopulmonary bypass (CPB) is necessary for coronary
artery bypass surgery; unfortunately, the inflammatory response
that results from its use may have detrimental consequences.
South Asian ethnicity is associated with increased mortality
after bypass surgery. The reason for this remains unclear, but
one possibility is that South Asians may react differently to
CPB. Accordingly, comparing the inflammatory response of South
Asians and Caucasians after cardiac surgery may yield an
explanation for the observed difference in mortality between
these populations.
Patients undergoing bypass surgery and who have given consent
will be enrolled. Blood samples will be collected before surgery,
after CPB has begun, and 1, 2, 4, 6, 12 and 24 hours after this.
The blood samples will be analyzed for the presence of various
inflammatory and anti-inflammatory mediators.
This is the first study to examine the mechanism whereby
ethnicity influences outcome after cardiac surgery. The results
will further the understanding of the inflammatory response
elicited by CPB, which may guide the design of specific therapies
to mitigate the effect of ethnicity on survival.
Dr. A. Archibald
Dr. S. Vanner
Queen’s University
The development of a protocol for colonoscopic monitoring of
live mice.
Inflammatory bowel disease is a serious and common clinical
disorder that affects millions of people, and it is monitored
through colonoscopy. Researchers have developed mouse models that
mimic this disease. Until recently, visualization of this colitis
required euthanization for histopathological analysis.
State-of-the-art mini-colonoscopes for mice have been recently
developed, so now an alternative to euthanasia exists.
This project represents the first use of this equipment. In this
study, the investigators will establish a safe and reliable
protocol for mouse colonoscopy. They plan to determine the
optimal choice of anesthetic agent, evaluate the correlation of
estimated scope position with actual anatomical location in the
mouse colon, assess the safety and efficacy of multiple colonic
biopsies over time, and test the ability of mouse colonoscopy to
reliably detect changes in the evolution of colitis by comparing
it to the current gold standard
Dr. A. D'Sa
Dr. P. Belliveau
Queen's University
Inhaled carbon monoxide in patients with post-operative ileus
following colon resection.
Post operative ileus (POI), a temporary paralysis of the
intestines, is a serious health care problem. It normally occurs
in all patients after surgery to the abdomen, but it can result
in serious complications in some cases.
The objective of this study is to determine if inhaling very low
doses of carbon monoxide (CO) before and after colon surgery will
shorten the duration of normal POI and/or prevent the development
of POI complications in patients undergoing colon surgery.
A preliminary study will be conducted in six healthy volunteers
to monitor for blood levels and adverse effects that occur at 3
different doses of inhaled CO to establish a safe dose for
patients in the main trial. For the main trial, patients
requiring surgery to their colon will be assigned randomly to
receive one hour treatments of either CO or oxygen by face mask
before and after their operation. Length of normal POI and
occurrence of POI complications will be compared between the two
groups. Side effects that occur from inhaling CO or oxygen will
also be recorded.
These investigators predict that inhaling CO before and after
colon surgery will shorten the length of normal POI and decrease
the occurrence of POI complications with minimal side effects.
Dr. S. Varma
Dr. S. SenGupta
Queen's University
The ezrin signalling network as a potential novel marker for
breast cancer metastasis.
Breast cancer is the most common cancer and foremost cause of
cancer deaths in Canadian women. Cancer spread to the lymph nodes
is a major determinant of the stage, treatment options, distant
spread and survival of the patient. However, few markers are
available to predict disease behavior in the absence of lymph
node involvement. Recently, subtypes of breast cancer have been
defined based on gene expression patterns. One such subtype is
‘basal-like’, which is an aggressive form of breast
cancer not amenable to usual therapies and has more potential for
spreading to various organs.
These investigators have discovered that an oncogene (a
cancer-causing gene) called Src interacts with a protein called
ezrin (that tethers the outer cell membrane to internal
cytoskeleton structures), thereby stimulating breast cancer cells
to spread to other parts of the body (termed metastasis). Recent
studies have indicated that this pathway may be involved in
breast cancer, particularly of the basal-like subtype. The first
objective of this study is to assess this pathway in metastasis
using a model of basal-like human breast cancer, and the second
objective is to evaluate the markers of this pathway in samples
from 450 breast cancer patients and their relationship to the
outcome of the disease (recurrence, distant spread and survival).
This study may lead to new approaches to the early detection and
treatment of metastatic breast disease.
Dr. M. Roberts
Dr. E. Grober
Mount Sinai Hospital
Intra-operative assessment of technical skill using economy
of hand motion: Establishing learning curves of surgical
competence.
Assessment of surgical skill has traditionally been subjective.
Recently, several methods for objectively evaluating surgical
competence have been developed; however, these have largely been
applied in the laboratory, and not in the live operating room.
The goal of this study is to evaluate a new technology - Hand
Motion Analysis (HMA) - for the objective assessment of surgical
skill inside the operating room, on real patients. HMA involves
tracking a surgeon’s hand movements and hand travel distance
using magnetic hand sensors. This technology will be applied to 3
common surgical procedures: vasectomy, microsurgical vasectomy
reversal and laparoscopic cholecystectomy. A large sample of
novice and experienced surgeons will be evaluated. Each operation
will be video-taped and surgical competence will be evaluated by
expert surgeons using previously validated assessment tools. HMA
data and expert surgeon assessments of technical skill will be
compared and used to generate learning curves of surgical
competency over time.
This information will prove useful as an evaluation and feedback
tool for surgical training programs, as trainees can learn where
they are on the “learning curve” as compared to expert
surgeons. Ultimately, this technology can be integrated into the
evaluation of practicing surgeons to improve surgical quality and
patient safety.
Dr. N. Etminan
Dr. L. Macdonald
St. Michael’s Hospital
Determination of the age of ruptured and unruptured
intracranial aneurysms.
Current epidemiological figures suggest that some aneurysms may
originate only weeks prior to rupture; ruptured aneurysms should,
therefore, consist to a great extent of new or young collagen,
while unruptured aneurysms should consist of mature collagen
types.
The investigators hypothesize that rupture of intracranial
aneurysms occurs as a result of instability and growth. The
objective of this study is to establish a method to date ruptured
and unruptured intracranial aneurysms in patients treated with
aneurysm clipping and excision.
Dr. L. Gaudet
Dr. M. Walker
University of Ottawa
Does maternal obesity modify pregnancy
outcomes for macrosomic infants.
Maternal obesity has been associated with
increased risks of pregnancy complications and adverse birth
outcomes such as gestational hypertension and preeclampsia and
gestational diabetes mellitus, Cesarean section delivery, fetal
overgrowth or macrosomia, and stillbirth. Large birth size, or
macrosomia, as defined by various birth weight only or
birth-weight-for-gestational age cutoffs, has been associated
with a number of birth complications and outcomes such as
C-section delivery, neonatal hypoglycemia, shoulder dystocia and
perinea trauma. Maternal obesity is a known risk factor for
having a macrosomic birth. There is a relative lack of knowledge
on whether maternal obesity may modify the effects of macrosomia
on the risks of pregnancy/birth outcomes.
These investigators proposed to assess whether the associations
between macrosomia and adverse birth complications/outcomes could
be modified by maternal obesity.
Dr. R. Gilbert
St. Michael’s Hospital
Cultured bone marrow derived cell therapy for progressive
chronic kidney disease.
Chronic kidney disease (CKD) is a growing problem in Canada, with
more than 30,000 patients suffering from end stage kidney
disease, and roughly two million Canadians diagnosed with, or at
risk of, kidney disease. Importantly, as CKD progresses, it is
associated with dramatic increases in risk of hospitalization and
death. Despite current therapies, a large proportion of CKD
patients still unfortunately progress.
The proposed translational studies aim to
provide evidence to support a new cell-based therapeutic strategy
to protect against progression of kidney disease. The specific
objectives of this proposal are to assess the ability of this new
cell-based therapeutic strategy to halt disease progression when
administered for advanced disease and to assess its additive
effect, when combined with current standard medications
(angiotensin converting enzyme inhibition) for advanced CKD. This
work, while animal-based, will provide critical information that
can not be generated ethically in humans, and will guide the
development of human studies.
Dr. E. Grober
Mount Sinai Hospital
Validation of Real-time, Intra-operative, Surgical Competence
(RISC) assessments linked to patient outcomes
The objective of this study is to determine if intra-operative
evaluations of surgical skill using Real-time, Intra-operative,
Surgical Competence (RISC) assessments predicts clinical and
operative outcomes in patients.
Lessons learned from this research will
contribute significantly towards the objective assessment of
technical skill in real operative settings, on real patients,
based on clinically-relevant patient outcomes. Similar
methodology can be applied to develop RISC assessments for a
variety of surgical procedures and disease states.
Dr. C. Hahn
Hospital for Sick Children
Nonconvulsive seizures among critically ill children: A
prospective study of prevalence, patient characteristics and
outcomes.
Seizures are a common cause of brain injury, yet they are
treatable and potentially preventable. Among critically ill
children in coma, the majority of seizures are nonconvulsive,
meaning they have no overt clinical signs. These unrecognized,
untreated seizures are likely contributing to poor
neurodevelopmental outcomes, with life-long consequences for
children, their families and society.
T
he objectives of this study are to measure
the prevalence of nonconvulsive seizures among comatose
critically ill children, to identify specific patient
characteristics associated with nonconvulsive seizures, and to
describe the outcomes of critically ill children who have
experienced nonconvulsive seizures.
This study will generate an unprecedented breadth and depth of
information on nonconvulsive seizures, which will inform the care
of critically ill children across Canada and internationally.
Dr. M. Hodaie
K. Davis, Ph.D
Toronto Western Hospital
Diffusion based tractography and
structural brain imaging in trigeminal neuralgia: correlation
with quantitative sensory testing and response to treatment.
Chronic pain can be a debilitating illness
that imposes great suffering and impacts quality of life, and
understanding the neuroanatoomical and pathophysiological changes
associated with chronic pain is crucial.
These investigators are hopeful that this study will advance
current understanding of the neuroanatomical changes in
neuropathic pain and help pave the way for better treatment for
patients.
Dr. A. Muinuddin*
Dr. W.G. Paterson
Queen's University
Barium esophagrams in eosinophilic
esophagitis: Identifying a narrow esophagus.
Eosinophilic esophagitis (EE) is a chronic
inflammatory condition that appears to be related to either food
or airborne allergy. Clinically, EE presents with symptoms of
difficulty in swallowing and food impaction in the esophagus. EE
is an increasingly recognized disease of the esophagus causing
significant morbidity and more commonly in young men. Imaging of
the esophagus with Barium esophagrams, a routinely used imaging
technique, can provide important information in the diagnosis and
management of esophageal disorders including EE. In EE patients,
several qualitative abnormalities have been noted on esophagrams
including narrowing of the esophagus, strictures and multiple
concentric rings, but in most instances the Barium esophagram is
reported as normal in these patients. Esophageal narrowing
producing a diffuse small-caliber esophagus is often more
difficult to recognize than shorter segments of narrowing, and
are highly interpreter dependent.
The aim of this project is to establish
what constitutes normal esophageal diameters along the length of
the esophagus and then compare this to patients with EE.
Objective measurement of esophageal diameter are currently not
routinely used in practice and may help to identify regions of
subtle esophageal narrowing and alert clinicians to potential EE
in the proper clinical setting, as well as to assist in planning
endoscopy.
Dr. V. Patel
Dr. J. Gregor
University of Western Ontario
The effect of intestinal proton-coupled
folate transporter (PCFT) expression on the disposition of
methotrexate.
Parenteral methotrexate is an effective
treatment for Crohn’s disease. Oral methotrexate is also
considered to be effective but has never been formally studied.
The oral form is used when the parenteral route is not tolerated
or preferred by the patient. However, studies of oral
bioavailability demonstrate a large amount of inter-individual
variability and less consistency than subcutaneous
bioavailability. Bioavailability refers to the fraction of the
drug that makes it into the systemic circulation unchanged. The
intestinal proton-coupled folate transporter (PCFT) is the drug
transporter (intestinal protein) that is likely responsible for
methotrexate absorption from the gastrointestinal tract.
This study will investigate the
relationship between duodenal PCFT expression in patients with
Crohn’s disease and methotrexate disposition (absorption and
distribution). The investigators will study the pharmacokinetic,
method for describing the dispositional time course of the drug
in the body, profiles of both oral and subcutaneous methotrexate.
They hypothesize that subjects with lower PCFT expression, lower
amounts of transporter in the intestinal wall, will have
decreased gastrointestinal absorption of oral methotrexate. The
results of this study may help explain the individual differences
in oral bioavailability demonstrated in previous studies, and
this knowledge may eventually help determine which patients will
be appropriate candidates for treatment with oral methotrexate,
thus potentially reducing problems with treatment failure and/or
medication side effects.
Dr. R. Poley
Dr. J. Newbigging
Queen's University
Can emergency physicians safely exclude
proximal DVT?
Large blood clots within the deep veins of
the leg (proximal DVTs) can break free and result in fatal
pulmonary embolus, making early diagnosis and treatment
imperative. Emergency physicians currently use clinical
information, a blood test (D-dimer) and, if both positive, a
formal ultrasound to make the diagnosis of DVT. Unfortunately,
formal ultrasound by a radiologist is not always immediately
available, and the blood test has many false positives, which
lead to delay in diagnosis, return visits for imaging, and
empirical treatment with blood thinners until the diagnosis can
be ruled out.
Emergency physicians are increasingly performing rapid ultrasound
tests at the bedside to rule in or rule
out several other potentially fatal conditions. These
investigators propose studying whether emergency physicians can
perform an abbreviated form of leg ultrasound to rule out DVT,
and they hope to prove that such targeted ultrasound testing by
the emergency physician results in fewer false positives than the
blood test in low risk patients, saving time, return visits,
unnecessary treatment and money. Moreover, they hope to prove
that, for high risk patients, this bedside ultrasound can be
combines with the blood test to reduce further testing and
diagnostic uncertainty.
Dr. A. Scheer
Dr. R. Boushey
University of Ottawa
The development and evaluation of a
patient decision aid for patients with mid and distal rectal
cancer.
The purpose of this study is to create and
evaluate a decision-support tool for patients with rectal cancer
faced with the decision of a permanent colostomy or bowel
re-attachment. Through needs assessment interviews with patients
and clinical experts, this project will identify the issues
concerning rectal cancer surgery decision making, and it will
provide a solution - a Patient Decision Aid, thereby moving
research into action.
The results this study will empower
patients with resectable rectal cancer to partake in
shared-decision making with their practitioners, and it will
enable patients to make informed, evidence- and values-based
decisions on the most appropriate surgical management of their
disease.
Dr. G. Smith
Queen’s University
Effect of carbon monoxide on placental function and
development.
Preeclampsia (PE) affects 5-10% of all pregnancies and is a
leading cause of maternal and neonatal morbidity and mortality
worldwide. It increases perinatal mortality five-fold, a
significant proportion of which is due to iatrogenic prematurity
as delivery is the only known way to reverse the syndrome.
This investigator have previously demonstrated that, ironically,
smoking during pregnancy decreases the risk of developing PE.
Experiments suggest that this is because of the increase in
carbon monoxide (CO). This investigator has recently demonstrated
that exposure to low doses of CO actually increases litter size
and maternal/fetal weight in pregnant mice.
The proposed studies will go a long way to
not only determining the etiology of this apparently beneficial
effect of low doses of CO but potentially developing therapeutics
that may be used to prevent and/or treat PE.
Dr. K-T. Tan
Toronto General Hospital
Local delivery of raclitaxel for prevention of restenosis in
hemodialysis access.
Narrowing of the draining vein occurs in more than 50% of
hemodialysis fistula and will lead to loss of access if left
untreated. This narrowing is due to excessive growth of tissue in
the vessel wall (intimal hyperplasia). The standard treatment is
balloon dilatation; however, narrowing will inevitably recur in
two to three months, requiring further dilatation. Intimal
hyperplasia also occurs in the heart and leg circulation. The
drug paclitaxel has been used with great success in preventing
intimal hyperplasia in these vessels following balloon
dilatation. Administer locally, paclitaxel inhibits excess tissue
growth in the vessel wall.
This investigator believes that this drug
will have similar effect in hemodialysis fistula. The objective
of this study is to assess the effect of paclitaxel in
hemodialysis access with narrowing. The results of this study may
decrease number of balloon dilatations and hence hospital
admissions, improve dialysis fistula function, and decrease
overall economic cost.
Dr. D. Wong
Toronto Western Hospital
Does boussignac CPAP compared to venturi mask improve
oxygenation and pulmonary function in morbidly obese patients
undergoing bariatric surgery?
Obesity has become a global epidemic. In Canada, there is a
growing number of bariatric surgeries performed after failure of
conventional treatment. Morbid obesity and general anesthesia
have additive and major negative impact on respiratory physiology
resulting in poor oxygenation and complications after bariatric
surgery. Boussignac CPAP mask is a new, simple, portable device
which can provide a controlled amount of positive pressure to the
lungs and has been shown to be beneficial for respiratory
function.
This study will be the first randomized
trial to assess the effectiveness of using Boussignac CPAP in
morbidly obese patients immediately after removal of the
breathing tube after bariatric surgery. It may reduce the
recovery room stay or need for the intensive care unit.
Dr. M. Alarab
Mount Sinai Hospital
Expression of modulators of collagen
and elastin remodeling in vaginal tissue of premenopausal women
with severe pelvic organ prolapse.
Pelvic floor dysfunction, including pelvic
organ prolapse (POP) and urinary incontinence, represent major
health issues for women in the reproductive and menopausal years.
Although the prevalence is as high as 50% in some reports, the
underlying mechanism and basic pathophysiology remains poorly
understood.
This study aims to test the hypothesis that
the expression of modulators of elastin and collagen differ in
premenopausal women affected by POP compared to asymptomatic
matched controls in the secretary phase of the menstrual cycle.
Dr. J. Barfett
Dr. D. Mikulis
Toronto Western Hospital
Quantification of Cerebral Aneurysm Deformation with the
Cardiac Cycle by Dynamic 4D Computed Tomography: Does Deformation
Correlate with Aneurysm Stability.
Cerebral aneurysms occur primarily in adults, and rupture of
cerebral aneurysms results in subarachnoid hemorrhage and can
lead to morbidity and mortality in those patients. The reason why
some aneurysms rupture (and why others do not) is not clearly
understood.
These investigators will use
dynamic“4D” CT (the fourth dimension being time) in
this study to provide a “deformation map” that will be
indicative of the change in aneurysm volume throughout the
cardiac cycle. The immediate aim of the project is to quantify
the deformation of the wall of a cerebral aneurysm through the
cardiac cycle using computerized tomography (CT) technology.
Quantified knowledge of aneurysm wall deformation will help
predict the propensity of an aneurysm to rupture.
Dr. J. Batt
St. Michael's HospitalMolecular
Mechanisms Underlying ICU-Acquired
Skeletal Muscle Dysfunction.
Treatment advances have led to improved
survival rates in individuals admitted to Intensive Care Units
(ICU), but the effects of both critical illness and therapies
administered during hospitalization persist beyond discharge and
frequently result in long term ICU-acquired muscle dysfunction.
This reduced muscle mass and weakness compromises quality of
life, an individual’s ability to return to work and
independent living, and increases health resource utilization and
costs. Studies in animal models of critical illness reveal that
activation of a protein degradation pathway within muscle known
as ubiquitin-proteasome mediated proteolysis, and diminished
mitochondria number and activity, are important causes of muscle
dysfunction. Interventions that inhibit these processes protect
muscle in animal models of critical illness.
This investigator hypothesizes that
sustained activation of ubiquitin-proteasome mediated
proteolysis, down-regulation of cellular processes that
counteract proteolysis and decreased muscle mitochondrial content
and activity occur in the skeletal muscle of patients with
ICU-acquired muscle dysfunction. Identification of the molecular
mechanisms underlying ICU-acquired muscle dysfunction will aid
development of effective therapeutic measures.
Dr. M.A.T. Bortolini
Dr. M. Alarab
Mount Sinai Hospital
Expression of Smooth Muscle Conractile
Machinery Proteins in the Vaginal Tissue of Women with and
without Pelvic Organ Prolapse.
The objective of this study is to analyze
the differential expression of five genes and proteins related to
smooth muscle (SM) contractile machinery in vaginal tissue of
patients with advanced Pelvic Organ Prolapse (POP) and control
patients.
This is the first study in the literature to analyze SM proteins
in vaginal tissue of a homogeneous group of Caucasian
premenopausal patients controlled by the phase of menstrual
cycle. This study will obtain more precise results that will
increase understanding of the molecular basis of the POP.
Dr. R.M. Gorczynski
Dr. G.A. Levy
University Health Network
A role for, and mechanism of action of,
sCD200 in transplant graft survival
Organ transplantation represents the
optimal treatment modality for end-organ failure, though
significant problems are associated with the non-specific
immunosuppression used to achieve successful graft survival,
including opportunistic infection, drug toxicity and malignancy.
Improved monitoring of host specific unresponsiveness to the
graft would facilitate attempts at early dose reduction and even
withdrawal of administered immunosuppressive drugs.
These investigators have reported at length
on the ability of a cell surface molecule, CD200, to foster
prolonged graft survival in a variety of experimental transplant
models and have recently identified that a soluble form of this
molecule, sCD200, is released into the serum of transplant
recipients, and graft survival is increased in animals with high
serum levels of sCD200. This observation suggests that monitoring
serum levels of soluble CD200 (sCD200) may provide a novel and
unique way to monitor transplant patients.
This research team proposes to measure,
both prospectively and retrospectively, sCD200 levels in cohorts
of liver transplant patients and correlate these values with
their immune and graft status and graft survival. They also plan
to correlate the structure/function of sCD200 in patients with
the mechanism(s) by which sCD200 modulates host immunity.
Dr. G.M.T. Hare
St. Michael's Hospital
B1-Adrenergic Antagonists Impair Murine
and Human Resistance Artery Function
B-blockers are drugs used to treat high
blood pressure and reduce the incidence of death following a
heart attack; however, these drugs have also been shown to
increase the incidence of ischemic organ injury and death in
surgical patients, despite their ability to protect the heart.
To define the mechanism of organ injury,
this investigator plans to assess the ability of B-blockers to
prevent small nutrient blood vessels from dilating. The current
study will define the mechanism by which B-blockers cause blood
vessel paralysis in mice by studying the effect of commonly used
B-blockers in appropriate genetic models. Moreover, this study
will determine if B-blockers can paralyze normal human blood
vessels, thereby contributing to observed increases in ischemic
organ injury and death rates observed in surgical patients
treated with these commonly used medications.
Dr. J. Marshall
Dr. K. Burns
St. Michael’s Hospital
Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial
Pandemic influenza poses a threat to human populations; moreover,
there is global concern that we are currently on the leading edge
of a larger pandemic season. A small percentage of patients
afflicted with H1N1 develop severe lung disease requiring
mechanical ventilation, and little is known about the optimal
treatment of these patients. Accumulating reports, however,
suggest that statins (cholesterol lowering medications) may be of
benefit in treating the most severely affected patients.
This research group proposes to conduct a multicentre, pilot,
randomized controlled trial in the general Intensive Care Units
(ICUs) of thirty national and international centres. In the
Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial,
comparing Rosuvastatin (Crestor™) to standard care, these
investigators will demonstrate the ability to recruit critically
ill adults with suspected, probable or confirmed H1N1 infection
requiring mechanical ventilation into the trial. These
investigators will also demonstrate that they can adhere to the
treatment regimen outlined in the study protocol and collect the
desired primary and secondary endpoints for the planned full CHAT
Trial.
Dr. L. McIntyre
Dr. D.J. Cook
McMaster University
PEMETRICS: Pulmonary Embolism:
Methodology, Epidemiology & Treatment In Critical Care Study
Blood clots developing because of
inactivity or serious illness may travel to the lungs. Clots in
the lung are extremely dangerous and are the leading cause of
hospital death. In a seriously ill patient, symptoms of a lung
clot vary depending on size, location, and a patient’s
overall health. When a patient is on life support, lung clots are
often unrecognized because many signs and symptoms of lung clots
are confused with other conditions. Tests to diagnose lung clots
are uncommonly done in a seriously ill patient, and results are
often unclear when preformed. Lung clots increase the time on
life support, increase the hospital stay, and the risk of death.
In this new research program, these
investigators will undertake several important studies on lung
clots during serious illness. They will study major problems that
previously have not been studied: the proper diagnosis, the
accuracy of doctors’ decision-making, risk factors and
consequences, and how drugs and devices help to treat lung clots.
The investigators plan to quickly and cost-effectively create new
knowledge about this life-threatening problem so that it can be
better identified, prevented, and treated.
Dr. D. Naudie
University of Western Ontario
Cost Effectiveness of Web-Based Follow-up Following Total
Joint Arthroplasty
Total joint arthroplasty (TJA) is a commonly performed procedure
that requires interval follow-up appointments. These visits often
involve patient costs, travel, and time, yet most often are brief
and rarely change the outcome of the patients care. On occasion,
an x-ray may identify a problem at one of these visits leading to
intervention, further follow-up, or even surgery. Complications
following total joint arthroplasty are rare, and the majority of
follow-up visits are routine. Technology now exists to conduct
annual research follow-up assessments without having to
physically see the patient.
This study will investigate the
cost-effectiveness of web-based follow-up assessments compared to
standard in-clinic follow-ups. The investigator will also assess
patient satisfaction, preference, and the validity of the
web-based follow-up assessments.
Online assessment could significantly decrease wait times in
orthopaedic clinics, as well as increase availability for
operating time and new consultations. This approach could
potentially reduce patient burden by decreasing travel distances,
financial burden, and time requirements.
Dr. J. Snowdon
Dr. T. Childs
Queen's University
Application of microRNA expression
profiles for prognostication in endometrial carcinoma
MicroRNAs (miRNAs) are regulatory molecules
that have been exploited for cancer diagnosis and prognosis.
Endometrial cancer is clinically classified as low, intermediate,
or high risk based on specific criteria. Intermediate risk
cancers have a 15-20% risk of recurrence, and patients are
offered radiotherapy after surgery in an effort to reduce this
risk.
The investigators hypothesize that using
miRNA expression profiling will distinguish between intermediate
risk cancers that have recurred versus those that have not. If
miRNA expression profiling can stratify intermediate risk cancers
into low and high risk subgroups, this may lead to a reduction in
unnecessary radiotherapy and associated morbidity.
Dr. V. Thiruganasambandamoorthy
Dr. I.G. Stiell
University of Ottawa
A Study to Derive a Clinical Decision
Rule to predict short-term serious outcomes in adult syncope
patients after Emergency Department discharge.
Syncope (fainting) is a common reason for
emergency visits with 100,000 patients visiting Canadian
emergency rooms (ER) annually, and approximately 10,000 of these
patients will suffer negative consequences, such as heat attack
or irregular heart rhythm requiring pacemaker/defibrillator or
even death. Half of these events occur after the patient leaves
the ER, and predicting such events poses a very difficult task.
Previous research by these investigators shows that one-third of
the time ER doctors were unable to predict those at risk, even
though it is feasible to do so.
This study aims to develop a rule to
accurately predict who will develop serious consequences when
discharged from the ER. A new rule will be tested by subsequent
research to confirm its ability to accurately predict negative
outcomes, and it will improve patient safety by admitting those
at risk, avoiding unnecessary admissions, and help doctors
quickly decide treatment, thereby improving wait times.
Dr. J. Yeung
Dr. S. El-Defrawy
Queen's University
Comparative case controlled study of
iris histological features in tamsulosin (Flomax) exposed eyes
A new disease entity known as
Intraoperative Floppy Iris Syndrome (IFIS) has threatened the
safety and success of cataract surgery. It is characterized by a
weakened iris that can slip out of the eye during surgery and be
difficult to reposition back into the eye, often leading to
surgical complications.
Currently, the cause of IFIS is unknown. Tamsulosin
(Flomax™), a common drug used to treat urinary diseases,
has been associated with IFIS. This medication targets cellular
receptors that are prominent in both the prostate and the iris.
Full understanding of how this drug affects the iris is vital to
developing treatments for IFIS.
This study aims to determine the cause of
IFIS by investigating the affects of Tamsulosin on iris muscle
architecture and cellular receptor production. These
investigators expect this research to contribute to the basic
understanding of Intraoperative Floppy Iris Syndrome; a necessary
step in developing IFIS treatments and making cataract surgery
safer.
Dr. B. Sharma
Dr. T. Grantcharov
St. Michael’s Hospital
Comparing three different Non Technical Skills Assessment
Tools in the Post Operative Setting
Surgical training presents a unique challenge to trainees. They
must learn technical skills in the operating room but also manage
patients on the floor, who are often acutely ill. Training
curriculum place great emphasis on medical knowledge and
improving technical expertise; however, little formal training
around non technical skills, such as communication, leadership,
and resource management occurs. In recent years, various rating
scales to assess non technical skills in the operating room have
been developed, but no consensus exists over which ones to use.
Additionally, most of the studies assessing their use have been
restricted to non technical skills assessment in the operating
room. The surgical community acknowledges evidence that adverse
events in surgery can be avoided by improving non technical
skills. It is, therefore, important that these skills be extended
beyond the operating room to the surgical floors, where patients
are critically ill and where a multi disciplinary team approach
is needed to effectively manage patients.
The aim of this study is to compare three
different non technical skills evaluation tools NOTSS, NOTECHS
and Ottawa GRS systems, using simulated post operative crisis
scenarios. Specifically, these investigators will determine how
reliable are each of the three behavioural rating scales at
assessing non medical/non technical skills, comment on the
validity of each of the three evaluation tools in the post
operative setting, if training improve resident performance as
assessed by the three different evaluation tools, and reach a
consensus on which tool to use, when evaluating surgical
residents' non technical skills as they apply to management of
post operative crisis situations. This project aims to develop a
validated and reliable evaluation tool for non-technical skills
in the clinical practice of surgery.
Dr. B. Yanagawa
Dr. S. Verma
St. Michael's Hospital
DJ-1 Signaling in Human Cardiac
Ischemia Reperfusion.
Despite advances in treatment and
prevention, heart attacks still represent a major economic,
societal, and healthcare burden. DJ-1 is a protein first
identified as a cancer-associated gene and subsequently
associated with an inherited form of Parkinson’s disease. It
plays important roles during times of oxygen deprivation, or
ischemia, but its function in the heart remains unclear.
The overall goal of this proposal is to
better understand the mechanism of ischemic injury in the heart,
as seen during a heart attack. The specific objective is to
determine how levels of DJ-1 and targets change in human hearts
undergoing surgical ischemic injury.
hese investigators will collect heart
tissues during surgery - both before and after the blood flow to
the heart is artificially stopped. Levels and localization of
DJ-1 and targets will be characterized using molecular techniques
and imaging studies. Insights gained from this study will shed
light on the mechanism of cardiac injury following a heart attack
and open new avenues for development of rational therapies.
Dr. A. Tang
Dr. S. Verma
St. Michael's Hospital
Neuregulin and Endothelial Dysfunction.
The hardening of arteries (atherosclerosis)
can lead to death. Atherosclerosis starts when the inner cell
lining of blood vessels (endothelial cells) become damaged and
the vessel loses its ability to expand. Since most treatments
focus on treating the disease in the later stages, strategies
targeting the early phase are necessary to ensure arteries remain
flexible.
Neuregulin-1 is a protein involved in the normal function of the
nervous system, and some types of neuregulin-1 can protect
against heart disease. This study aims to discover if
neuregulin-1 can protect endothelial cells and preserve the
ability of blood vessels to expand.
The results of this study will inform if
neuregulin-1 protects against atherosclerosis and may provide a
new way to prevent cardiovascular disease.