Mobilising Expertise And Resources To Close The Radiotherapy Gap In Cancer Care., D Rodin, J Longo, T Sherertz, M M Shah, O Balagun, N Wendling, Jacob Van Dyk, C N Coleman, M J Xu, S Grover

Oncology Publications

Closing the gap in cancer care within low- and middle-income countries and in indigenous and geographically isolated populations in high-income countries requires investment and innovation. This is particularly true for radiotherapy, for which the global disparity is one of the largest in healthcare today. New models and paradigms and non-traditional collaborations have been proposed to improve global equity in cancer control. We describe recent initiatives from within the radiation oncology community to increase access to treatment, build the low- and middle-income countries' radiation oncology workforce, mobilise more professionals from within high-income countries and raise awareness of the global need for …

Analysis Of Global Radiotherapy Needs And Costs By Geographic Region And Income Level., E Zubizarreta, Jacob Van Dyk, Y Lievens

Oncology Publications

Recent years have seen various reviews on the lack of access to radiotherapy often based on geographic regions of the world such as Africa, Asia Pacific, Europe, Latin America and North America. Countries are often defined by their national income per capita levels based on World Bank definitions of high income, upper middle income, lower middle income and low income. Within the world regions, there are significant variations in gross national income (GNI) per capita among the different countries, and even within similar income levels, large variations exist. This report presents the actual status of radiotherapy and analyses the current …

The Role Of Scapular Morphology In Reverse Shoulder Arthroplasty, Ashish Gupta

Electronic Thesis and Dissertation Repository

Baseplate fixation in a reverse shoulder arthroplasty depends on adequate bone stock. In cases of severe glenoid bone loss and revision shoulder arthroplasty, deficiency of the glenoid vault compels the surgeon to attain screw fixation in the three columns of the scapula. The relationship of these columns demonstrated that the coracoid is closer to the lateral scapular pillar in females than in males. Significant gender dimorphism exists between the orientations of the three columns. The gender dimorphism is further evaluated by anthropometric measurements of the scapular body and the glenoid. The clinical significance lies in the ability to reconstruct the …

Paediatric Surgical Outcomes Across Ontario, Damian Dylkowski

Electronic Thesis and Dissertation Repository

BACKGROUND: The purpose of this study was to determine the volume of three complex paediatric procedures at the tertiary care centres in Ontario over the last 20 years in three disciplines, analyze outcomes and explore the possibility of an outcome volume relationship.

METHODS: A population based cohort study of patients undergoing TEF repair, Pyeloplasty and V-P shunt insertion at 4 paediatric centres in Ontario between 1993 and 2013 was carried out. Administrative data sets were linked using unique encoded identifiers and analyzed at the Institute for Clinical Evaluative Sciences (ICES).

RESULTS: In TEF repair and Pyeloplasty, there was significant difference …

Detection Of Α-Thalassemia By Using Multiplex Ligation-Dependent Probe Amplification As An Additional Method For Rare Mutations In Southern Turkey, Ozge Ozalp Yuregir, Akif Ayaz, Sinem Yalcintepe, Sezin Canbek, Didar Yanardag Acik, Basak Taburoglu Yilmaz, Tugce B. Balci

Paediatrics Publications

α-thalassemia is the most common single gene disorder in the Cukurova Region in Turkey. It is therefore routinely screened, including premaritally, in our region. The heterogeneous molecular basis of the disease makes α-thalassemia mutation detection difficult and complex. Besides well established methods, multiplex ligation dependent probe amplification (MLPA) is known as an effective, simple and specific method for the detection and characterization of deletions and duplications. We employed MLPA testing to 30 patients with hematological parameters suggestive of α-thalassemia carrier status but was negative for α-thalassemia with conventional reverse dot blot hybridization (RDB). We found α-globin gene deletions in 3 …

Physical Activity Levels In Total Hip Arthroplasty Comparing The Direct Anterior Approach To The Direct Lateral Approach: A Prospective Cohort Study, Abdulaziz N. Aljurayyan

Electronic Thesis and Dissertation Repository

Total hip arthroplasty (THA) is a cost-effective surgical procedure to treat patients with end-stage hip arthritis with high patient satisfaction. Different surgical approaches to the hip have been used to successfully perform THA. However, the role of these surgical approaches on physical activity and early functional recovery in THA patients remains controversial.

In this thesis, we prospectively evaluated physical activity levels in patients with end-stage hip OA whom are undergoing elective THA. The primary focus was to evaluate the impact of different surgical approaches on physical activity levels as a measure of functional recovery in the immediate postoperative period.

Due …

Translational Study Of Liver Cancer And Hypertrophy: Translich, Mauro Enrique Tun Abraham

Electronic Thesis and Dissertation Repository

Abstract

Background: Associating liver partition with portal vein ligation for staged-hepatectomy (ALPPS) is a technique for inducing accelerated hypertrophy in patients with insufficient future liver remnant (FLR). It remains unknown whether this hypertrophy may lead to rapid cancer cell dissemination and/or alteration of immune cell/function reconstitution in the FLR. We aimed to determine if the rapid hypertrophy during ALPPS procedure results in more circulating tumour cell (CTCs) dissemination and whether the FLR remains immunologically competent in patients with CRLM.

Methods: In our prospective, observational, 2-arm study, we assessed the utility of CTCs as an evaluation tool for disease dissemination. Moreover, …

Accuracy Requirements And Uncertainties In Radiotherapy: A Report Of The International Atomic Energy Agency., Debbie Van Der Merwe, Jacob Van Dyk, Brendan Healy, Eduardo Zubizarreta, Joanna Izewska, Ben Mijnheer, Ahmed Meghzifene

Oncology Publications

BACKGROUND: Radiotherapy technology continues to advance and the expectation of improved outcomes requires greater accuracy in various radiotherapy steps. Different factors affect the overall accuracy of dose delivery. Institutional comprehensive quality assurance (QA) programs should ensure that uncertainties are maintained at acceptable levels. The International Atomic Energy Agency has recently developed a report summarizing the accuracy achievable and the suggested action levels, for each step in the radiotherapy process. Overview of the report: The report seeks to promote awareness and encourage quantification of uncertainties in order to promote safer and more effective patient treatments. The radiotherapy process and the radiobiological …

Radiation Oncology Quality And Safety Considerations In Low Resource Settings: A Medical Physics Perspective, Jacob Van Dyk, Ahmed Meghzifene

Oncology Publications

The last few years have seen a significant growth of interest in the global radiation therapy crisis. Various organizations have quantified the need and are providing aid in support of addressing the shortfalls existing in many low-to-middle income countries (LMICs). With the tremendous demand for new facilities, equipment and personnel, it is very important to recognize the quality and safety challenges and to address them directly. An examination of publications on quality and safety in radiation therapy indicates a consistency in a number of the recommendations; however, these authoritative reports were generally based on input from high-resourced contexts. Here we …

Cost-Effectiveness Of Selective Laser Trabeculoplasty (Slt) Versus Argon Laser Trabeculoplasty (Alt) In Uncontrolled Open Angle Glaucoma Patients Having At Least One Full Previous Slt: An Economic Evaluation Alongside An Ongoing Randomized Controlled Clinical Trial, Muhammad Rakibuz-Zaman

Electronic Thesis and Dissertation Repository

Background and objective: ALT and SLT are both safe and effective for glaucoma treatment. We performed a cost-effectiveness analysis (CEA) of SLT versus ALT for a six-month follow-up period in uncontrolled open angle glaucoma patients having at least one full previous SLT from an ongoing RCT. Methods: Trial based treatment costing and IOP reduction at 6-month follow-up from baseline for both intervention arms were calculated. A decision tree model was developed considering possible clinical pathways of patients undergoing repeat laser trabeculoplasty. CEA among ALT and SLT was done, and ICERs were calculated from both societal and ministry perspective. One way …

Early Experimental Results Of Using A Novel Delivery Carrier, Hyaluronan-Phosphatidylethanolamine (Ha-Pe) Which May Allow Simple Bladder Instillation Of Botulinum Toxin A As Effectively As Direct Detrusor Muscle Injection., Mohamed G. El Shatoury

Electronic Thesis and Dissertation Repository

Intra-detrusor Botulinum Toxin-A (BTX-A) injection is the gold standard treatment for detrusor overactivity in clinical practice when medical treatment fails. Despite satisfactory results of BTX-A injection, the endoscopic procedure still has risks of anaesthetic and operative complications. Several studies have investigated more simple ways to deliver BTX-A to the detrusor muscle but with limited success. In our study, we assessed the evidence of BTX-A delivery using a newly modulated hyaluronan-phosphatidylethanolamine (HA-PE) carrier in a rat model through BTX-A-HA-PE bladder instillations. We used histological evidence of SNAP-25 protein cleavage and detection of Alexa FluorÒ594-labelled BTX-A as a proof of physical BTX-A …

Structural Conservation And E2f Binding Specificity Within The Retinoblastoma Pocket Protein Family, Tyler J. Liban, Michael J. Thwaites, Frederick A. Dick, Seth M. Rubin

Paediatrics Publications

The human pocket proteins retinoblastoma (Rb), p107, and p130 are critical negative regulators of the cell cycle and contribute to tumor suppression. While strong structural conservation within the pocket protein family provides for some functional redundancy, important differences have been observed and may underlie the reason that Rb is a uniquely potent tumor suppressor. It has been proposed that distinct pocket protein activities are mediated by their different E2F transcription factor binding partners. In humans, Rb binds E2F1–E2F5, whereas p107 and p130 almost exclusively associate with E2F4 and E2F5. To identify the molecular determinants of this specificity, we compared the …

Global Access To Radiation Therapy For Cervical Cancer: The Cost Of Inaction, Jacob Van Dyk, D Rodin, Timothy Paul Hanna, E Burger, Eduardo Zubizarreta, Mei Ling Yap, Michael Barton, Rifat Atun, Felicia Marie Knaul, Y Lievens, Mary K. Gospodarowicz, D A. Jaffray, M Milosevic

Oncology Publications

No abstract provided.

Biallelic Hypomorphic Mutations In A Linear Deubiquitinase Define Otulipenia, An Early-Onset Autoinflammatory Disease, Qing Zhou, Xiaomin Yu, Erkan Demirkaya, Natalie Deuitch, Deborah Stone, Wanxia Li Tsai, Hye Sun Kuehn, Hongying Wang, Dan Yang, Yong Hwan Park, Amanda K. Ombrello, Mary Blake, Tina Romeo, Elaine F. Remmers, Jae Jin Chae, James C. Mullikin, Ferhat Güzel, Joshua D. Milner, Manfred Boehm, Sergio D. Rosenzweig, Massimo Gadina, Steven B. Welch, Seza Özen, Rezan Topaloglu, Mario Abinun, Daniel L. Kastner, Ivona Aksentijevich

Paediatrics Publications

Systemic autoinflammatory diseases are caused by mutations in genes that function in innate immunity. Here, we report an autoinflammatory disease caused by loss-of-function mutations in OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one frameshift mutations in one Pakistani and two Turkish families with four affected patients. Patients presented with neonatal-onset fever, neutrophilic dermatitis/panniculitis, and failure to thrive, but without obvious primary immunodeficiency. HEK293 cells transfected with mutated OTULIN had decreased enzyme activity relative to cells transfected with WT OTULIN, and showed a substantial defect in the linear deubiquitination of target molecules. Stimulated patients' …

The Role Of Postural Stability And Other Factors In Distal Radius Fracture, Sheena Saju Philip

Electronic Thesis and Dissertation Repository

The objective of the thesis was to describe the factors leading to falls in distal radius fracture (DRF) events, explore patient perceived risk of falls, and postural stability. A mixed method study described the type of fall in DRF patients (n= 1454) and patient perceived contributing factors (n=29). A prospective cohort study examined the postural stability and related fall risk of DRF participants (n=137) in Biodex Balance System (BBS) and compared to normative values. Environmental factors were a major contributor to DRF events. Older adults (44 to 65 years) had the highest rate of DRF (female: male ratio of 2:1). …

Reliability And Validity Of The Star Excursion Balance Test For Patients With Chronic Patellar Instability, Andrew D. Firth

Electronic Thesis and Dissertation Repository

The Star Excursion Balance Test (SEBT) is an eight-direction, maximal-reach balance test whose measurement properties are unknown in participants with chronic patellar instability. We designed an observational study with repeated measures to evaluate the test-retest reliability, cross-sectional and longitudinal construct validity, sensitivity to change and responsiveness of the SEBT in this population. Fifteen patients completed the SEBT and reported outcomes at baseline and two weeks and four patients completed testing three months later at the Fowler Kennedy Sports Medicine Clinic.

Intra-class correlation coefficients (ICC) for the SEBT were fair to good, ranging from 0.66-0.84. The SEBT demonstrates good cross-sectional construct …

Drop Vertical Jump Landing Mechanics Following Anterior Cruciate Ligament Reconstruction With And Without Lateral Extra-Articular Tenodesis, Michal Daniluk

Electronic Thesis and Dissertation Repository

The use of combined anterior cruciate ligament (ACL) plus lateral extra-articular tenodesis (LET) reconstruction has shown promising results during clinical testing, however, no studies have examined its effectiveness during a dynamic functional task. We used the drop vertical jump (DVJ) to compare in vivo biomechanics of ACL reconstructed patients with and without LET.

Our primary outcome was peak knee abduction moment during stance phase. Secondary kinetic and kinematic outcomes included peak initial contact and stance values for knee abduction angle, knee flexion moment and angle, knee internal rotation moment and angle, and vertical ground reaction force. We also assessed fear …

A Randomized Controlled Trial To Establish Realistic Patient Expectations Following Total Knee Replacement Surgery, Sharon E. Culliton

Electronic Thesis and Dissertation Repository

Objectives: To evaluate whether e-learning videos can affect whether patients felt their expectations were met and were satisfied with surgery 1 year following primary total knee replacement (TKR) (Chapter 3). In Chapter 4, we described characteristics of users and utilization patterns of the e-learning tool. In Chapter 5, we evaluated the internal consistency and construct validity of the new Knee Society Knee Scoring System (KSS) in a sample of TKR patients.

Methods: We recruited consecutive patients with osteoarthritis from the London Health Sciences Centre, Ontario, Canada (Chapter 3). We randomized patients with osteoarthritis to either control (n=207) they received our …

Evaluating The Effects Of Patellofemoral Offset Changes And Trochlear Design In Total Knee Arthroplasty: A Radiographic, Visual, And Topographical Analysis, Jacob Matz

Electronic Thesis and Dissertation Repository

Total knee arthroplasty (TKA) is a common procedure for the treatment of advanced knee osteoarthritis. Complications involving the patellofemoral joint (PFJ) are common following TKA, and the etiology is controversial. The purpose of this thesis was to evaluate two potentially modifiable factors affecting the PFJ: (i) changes in patellofemoral offset (PFO) and (ii) trochlear design.

Through a retrospective radiographic review, we demonstrated that PFO changes occur frequently post-TKA, and that the PFJ can tolerate these changes without adverse clinical outcomes. Retrieval analysis provided additional evidence that PFO changes are not associated with femoral component surface damage or wear.

In order …

Clinical And Cost-Effectiveness Of A Locking Versus Non-Locking Fixation Plate In Medial Opening Wedge High Tibial Osteotomy, Codie Primeau

Electronic Thesis and Dissertation Repository

We investigated the clinical and cost-effectiveness of using a locking versus non-locking fixation plate in medial opening wedge high tibial osteotomy (HTO) for patients with medial compartment knee osteoarthritis. Medical charts were retrospectively reviewed up to 12 months following HTO for 144 patients who received a locking plate and 105 patients who received a non-locking plate. Surgeon notes provided the time to return to full weight- bearing. Participants had completed the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively, six and 12 months postoperatively. Hospital and provincial administrative databases provided direct and indirect cost data. Improvements in KOOS scores were …

Body And Organ Measurements In Infants And Neonates: An Autopsy Study, Audrey-Ann M. Evetts

Electronic Thesis and Dissertation Repository

Abstract

Introduction: A pathologist doing a pediatric autopsy will commonly assess child’s development by comparing the postmortem data to standardized population parameters using body and organ measurement charts. Although a number of resources are available, many are outdated and have significant limitations.

Objectives: To create Ontario population-specific organ and body measurement mean charts for infants and to explore relationships between body measurements/organ weights and cause of death, age, and gender of the deceased.

Methods: A database of 900 cases of infant and neonatal deaths that were investigated by Ontario coroners from 2000 to 2010 was retrospectively analyzed.

Results and Conclusions: …

Protective Benefits Of Hydrogen Sulfide Treatment During Renal Transplantation, Ian Lobb

Electronic Thesis and Dissertation Repository

Ischemia/reperfusion injury (IRI) is inherent to renal transplantation (RTx) and is initiated when blood supply is necessarily removed during organ procurement (ischemia) and subsequently restored upon engraftment (reperfusion). During renal ischemia, ATP depletion causes tubular epithelial cell (TEC) injury and subsequent release of pro-inflammatory mediators. Upon reperfusion, influx of O₂ causes reactive oxygen species (ROS) production and infiltration of innate immune cells which release damaging ROS and proteases. Prolonged periods of IRI are associated with increased risk of delayed graft function (DGF) and decreased long-term graft survival. The endogenously produced gasotransmitter, hydrogen sulfide (H₂S), has recently been …

Investigating Stromal Contributions To The Regulation Of Cancer Progression, Krista M. Vincent

Electronic Thesis and Dissertation Repository

Tumours are not insular masses of proliferating cells, rather tumour cells evolve within a complex local environment complete with matrix, stromal, and immune components. Therefore, successful tumour growth and eventual metastasis is not determined solely by tumour cells themselves, but also by the fitness advantage or disadvantage conferred by their local environment. However, many of our current cancer models are composed solely of tumour cell isolates. As tumour fitness is dependent on the entire local cellular context, we were interested in characterizing the accuracy of cell lines as models of the tumour microenvironment, with a focus on the secreted Frizzled-related …

Measuring Engagement Of The Executive Control Network From 3 Months Of Age, Michelle Tran

Electronic Thesis and Dissertation Repository

The executive control network (ECN) is critical for higher cognition and executive function (EF). Despite its importance, no scientific consensus has been reached on how and when it begins to function. In the present study, we assessed the development of the ECN in awake infants less than a year old by employing functional magnetic resonance imaging (fMRI) and naturalistic stimuli. First, we identified evocative movies that engaged infant attention. We then transferred them into adult imaging to test for which movie evoked the highest ECN response. Strong ECN responses were evoked while viewing Despicable Me, therefore we implemented this …

Beta Blocker Dialyzability And Effectiveness In Chronic Hemodialysis Patients, Alvin Tieu

Electronic Thesis and Dissertation Repository

Of the minimal information describing drug dialyzability, the majority was obtained prior to modern hemodialysis membranes. This study characterized the dialyzability of the most commonly prescribed beta blockers in patients undergoing high-flux hemodialysis. Eight subjects were recruited to a pharmacokinetic, 4-way crossover trial. Drug concentrations were measured using mass spectrometry and dialyzability determined by the arterial-venous difference and recovery clearance methods. A provincial-wide retrospective cohort study was designed to determine the effect of dialyzability on adverse clinical outcomes. Beta blocker efficacy can be hindered if substantial clearance occurs during dialysis. Our results demonstrate atenolol and metoprolol are extensively cleared during …

Inpatient Versus Outpatient Total Hip Arthroplasty, Michael Pollock

Electronic Thesis and Dissertation Repository

We conducted a randomized controlled trial to evaluate patients undergoing a total hip arthroplasty (THA) who were discharged from the hospital either on the day of surgery (outpatient) or were admitted overnight following surgery (inpatient). Our primary outcome was the rate of serious adverse events during the first three months postoperatively. Secondary outcome measures included cost, patient satisfaction, functional outcomes, quality of life and pain. We found no statistically significant difference between the two groups in serious adverse events. We found that outpatient THA was less expensive from the perspectives of the hospital and ministry of health; but the difference …

Effects Of American Ginseng On Preimplantation Development And Pregnancy In Mice., Danyka Belanger, Michele D Calder, Alessandra Gianetto-Berruti, Edmund M Lui, Andrew J Watson, Valter Feyles

Obstetrics & Gynaecology Publications

In North America, a high proportion of pregnant women use herbal medications including North American ginseng. This medicinal plant contains high amounts of triterpene saponins (ginsenosides), which are the main bioactive compounds. It is important to assess ginseng's impact on all reproductive functions to ensure the safety of pregnant women and fetuses. In this study, we defined the concentration-responsive effects of North American alcoholic and aqueous ginseng extracts on preimplantation development in vitro and on pregnancy and post-partum development in the mouse. Two-cell mouse embryos were cultured with 5 different concentrations of whole ginseng root extracts, or ginsenosides Rb1, Rg1 …

Optimizing Respiratory Gated Intensity Modulated Radiation Therapy Planning And Delivery Of Early-Stage Non-Small Cell Lung Cancer, Ilma Xhaferllari

Electronic Thesis and Dissertation Repository

Stereotactic ablative body radiotherapy (SABR) is the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. However, thoracic tumours are susceptible to respiratory motion and, if unaccounted for, can potentially lead to dosimetric uncertainties. Respiratory gating is one method that limits treatment delivery to portions of the respiratory cycle, but when combined with intensity-modulated radiotherapy (IMRT), requires rigorous verification. The goal of this thesis is to optimize respiratory gated IMRT treatment planning and develop image-guided strategies to verify the dose delivery for future early-stage NSCLC patients.

Retrospective treatment plans were generated for various IMRT delivery techniques, including …

Assessment Of Post-Treatment Imaging Changes Following Radiotherapy Using Magnetic Susceptibility Techniques, Jean-Guy Belliveau

Electronic Thesis and Dissertation Repository

Radiation therapy (RT) is a common treatment for brain neoplasms and is used alone or in combination with other therapies. The use of RT has been found to be successful in controlling tumors and extending the overall survival of patients; however, there are many unanswered questions regarding radiotherapy effects in the normal brain surrounding or infiltrated by tumor. Changes to the vascular and parenchyma have been documented, and more recently inflammatory mechanisms have been postulated to play a role in radiation injury. Traditional imaging techniques used within the clinic (CT and MRI) are often lacking in their ability to differentiate …

Development Of Holistic Classification Systems For Children With Cerebral Palsy, Deepa Jeevanantham

Electronic Thesis and Dissertation Repository

Cerebral palsy (CP) is a complex disorder. There is a gap in the literature in classifying children with CP broadly. The purpose of this thesis was to develop holistic classification systems for children with CP. As a first step, a search was conducted to explore the strategies used to classify children with developmental co-ordination disorder and autism-spectrum disorder. Two versions of holistic classification systems named the body function index in cerebral palsy (BFI-CP) versions I and II were developed using two methods. Then, the relationship and differences among the developed classification systems and the Gross Motor Function Classification System (GMFCS) …