Medicine and Health Sciences Commons^™

Assessing Inflammation In The Pathology Of Knee Osteoarthritis, Zachary J. Koudys

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a joint disease that causes pain, stiffness, and loss of function. Inflammation of the synovium plays a role in the pathology of OA. Macrophages are the dominant immune cells in synovial tissue. Activated macrophages over-express the translocator protein (TSPO). [¹⁸F]FEPPA is a 2^nd generation positron emission tomography (PET) tracer that can target TSPO with high specificity. Hybrid [¹⁸F]FEPPA PET/MRI may enable accurate quantification of macrophage activity in vivo. In this work, [¹⁸F]FEPPA tracer uptake in knee synovial tissue was measured ex vivo using autoradiography and was validated to correlate to …

To Develop A Clinically Friendly Multi-Segment Kinematic And Kinetic Foot Model And Test It On Pre-/Post-Hto Patients With Medial Knee Osteoarthritis And Knee Varus, Songlin Zhu

Electronic Thesis and Dissertation Repository

This study aims to develop a clinically useful multi-segment foot model that will enable the analysis of foot kinematics and kinetics in an optical motion capture laboratory setting. This study will also test the new multi-segment foot model on patients with knee osteoarthritis and varus knee alignment that is corrected by high tibial osteotomy (HTO). The multi-segment foot model divides the foot into four functional segments: the hindfoot, midfoot, forefoot and hallux. An X-Z-Y-Cardan angle rotation convention was used to determine intersegmental dorsi/plantar flexion, inversion/eversion, and internal/external rotation. Joint moments, joint powers and medio-longitudinal arch (MLA) height/length ratio were also …

Three-Dimensional Ultrasound Imaging For Characterization Of Synovitis In First Carpometacarpal Osteoarthritis, Carla Du Toit

Electronic Thesis and Dissertation Repository

First carpometacarpal osteoarthritis is one of the most common forms of OA and is a significant source of pain and disability for patients. Discrepancies between traditional imaging modalities and patient reported outcomes have led galvanized researchers to developing objective point of care based imaging tools for assessing OA progression and treatment response. This thesis aims to describe the development and validation of a semi-submerged mechanical three-dimensional ultrasound device against magnetic resonance imaging. The validation of the 3D US device was conducted on a series of imaging phantoms, as well as ten CMC1 OA patients. Two-raters manually segmented areas of synovial …

The Cost-Effectiveness Of A Midvastus Versus Standard Medial Parapatellar Surgical Approach For Total Knee Arthroplasty, Ishita Joshi

Electronic Thesis and Dissertation Repository

The minimally invasive midvastus (MMV) surgical approach for total knee arthroplasty (TKA) is a less invasive technique that has been proposed to accelerate recovery over standard TKA, however, advantages are not yet definitively established. We investigated the cost-effectiveness of MMV TKA versus the standard medial parapatellar (MPP) approach for TKA alongside a randomized controlled trial in patients with knee osteoarthritis. Patients reported resource use as well as indirect costs, and health outcomes were measured using the EQ-5D-5L and the Western Ontario and McMaster Universities Osteoarthritis Index over the 12-month study period. The results of our net benefit regression analysis suggest …

Three-Dimensional Ultrasound Imaging For Quantifying Knee Cartilage Volume, Samuel Papernick

Electronic Thesis and Dissertation Repository

Arthritis is the most common chronic health condition in Canada, with the most common form being osteoarthritis (OA). There is a great clinical need for an objective imaging-based point-of-care tool to assess OA status, progression, and response to treatment. This thesis aims to validate a handheld mechanical three-dimensional (3D) ultrasound (US) device against the current clinical standard of magnetic resonance imaging (MRI) for quantifying femoral articular cartilage (FAC) volume. Knee images of 25 healthy volunteers were acquired using 3D US and 3.0 Tesla MRI scans. Two raters manually segmented the trochlear FAC during separate sessions to assess intra- and inter-rater …

Reducing Length Of Stay After Total Hip And Knee Arthroplasty: Assessing Cost-Effectiveness, Caregiver Involvement And Surgical Approach, Bryn O. Zomar

Electronic Thesis and Dissertation Repository

Purpose

The overall purpose of this dissertation was to evaluate factors related to reducing length of stay after total hip and knee arthroplasty (THA and TKA).

Methods

Study 1 was a randomized controlled trial (RCT) to investigate the cost-effectiveness of outpatient THA compared to standard overnight stay. Study 2 was a prospective cohort study to assess patient- and caregiver-related factors and how they may relate to caregiver strain and level of assistance when caring for patients undergoing THA and TKA. Finally, Study 3 was a 2x2 factorial RCT to compare the trajectory of early functional recovery between the medial parapatellar …

Joint Protection Programs For People With Hand Arthritis, Pavlos Bobos

Electronic Thesis and Dissertation Repository

The fact that Joint Protection Programs (JPP) can reduce pain and improve function is based on small, but definitive Randomized Controlled Trials (RCTs), conducted in the 1980s. However, changes over time in the nature of hand use, the rapid expansion of technology, and improvements in our understanding of health literacy mean that these programs are now outdated. Further, problems with adherence to JPP are well documented. The purpose of this thesis was 1) to conduct a scoping review to map all the available evidence around joint protection programs in published and unpublished studies 2) to evaluate the effectiveness of joint …

Quantitative Magnetic Resonance Imaging Of Knee Articular Cartilage And Effusion-Synovitis: The Structural Response To Changes In Joint Loading, Hayden F. Atkinson

Electronic Thesis and Dissertation Repository

Knee osteoarthritis (OA) is a progressive degenerative condition that can affect all tissues within the joint. Methods to measure early changes in joint structures and the effect of interventions are required. The purpose of this thesis was to investigate aspects of quantitative magnetic resonance imaging (MRI) as outcome measures in knee OA studies. Specifically, changes in articular cartilage composition and/or effusion-synovitis were examined in people with or at risk for knee OA and healthy controls, and after altering joint loads.

Chapter 2 is a systematic review that studied articular cartilage composition using MRI T2 and T1ρ relaxation in patients at …

Evaluation Of The Construct Validity Of The Questionnaire To Identify Knee Symptoms Among Individuals Across Canada With Chronic Knee Pain, James Young

Electronic Thesis and Dissertation Repository

The primary purpose of this study was to evaluate the construct validity of the Questionnaire to Identify Knee Symptoms (QuIKS) measurement scale among individuals with chronic knee symptoms consistent with osteoarthritis. Construct validity was assessed using tests of convergent and discriminative validity on 15 pre-specified hypotheses. The secondary objective was to determine the internal consistency reliability of the QuIKS. One hundred and five individuals recruited in select physiotherapy clinics from across Canada were mailed the QuIKS and five other health questionnaires. Fifty-five individuals completed the questionnaire package. While none of the pre-specified construct validity hypotheses were met, nine of the …

Quantitative Analysis Of Three-Dimensional Cone-Beam Computed Tomography Using Image Quality Phantoms, Rudy Baronette

Electronic Thesis and Dissertation Repository

In the clinical setting, weight-bearing static 2D radiographic imaging and supine 3D radiographic imaging modalities are used to evaluate radiographic changes such as, joint space narrowing, subchondral sclerosis, and osteophyte formation. These respective imaging modalities cannot distinguish between tissues with similar densities (2D imaging), and do not accurately represent functional joint loading (supine 3D imaging). Recent advances in cone-beam CT (CBCT) have allowed for scanner designs that can obtain weight-bearing 3D volumetric scans. The purpose of this thesis was to analyze, design, and implement advanced imaging techniques to quantify image quality parameters of reconstructed image volumes generated by a commercially-available …

Wearable Sensors And Total Knee Arthroplasty: Assessing Quantitative Function To Improve The Patient Experience, Megan Fennema

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a chronic degenerative disease for which the only long-term solution is total knee arthroplasty (TKA), though many patients are not satisfied with their TKA. Satisfaction in TKA patients is not well understood. Subjective questionnaires and objective functional tests have been previously used to assess TKA outcomes, but both have disadvantages. Wearable sensors have facilitated affordable biomechanical measurement in OA and TKA populations. The objective of this work was to use wearable sensors alongside functional tests with TKA patients to identify quantitative function that related to subjective function and satisfaction. A wearable sensor-setup was validated before implementation in …

Wait Times, Resource Use And Patient-Reported Outcomes For Patients Referred For Total Knee Replacement Surgery, Kate Lebedeva

Electronic Thesis and Dissertation Repository

This prospective cohort study evaluated the usual care pathway for patients referred to total knee arthroplasty (TKA). We measured healthcare resource use, costs and health-related quality of life (HRQoL) over the continuum of care. We also determined the proportion of inappropriate referrals and estimated wait times for initial surgical consultation and TKA. We found that two in five patients referred to specialty care were deemed inappropriate surgical candidates. Prior to referral, few conservative treatment options were tried, and many imaging tests ordered by referring providers were unjustified. Overall, the greatest proportion of costs were borne by the patient or private …

Assessing The Risk Of Falling In Adults One-Year After Total Hip Arthroplasty, William Janes

Electronic Thesis and Dissertation Repository

The purpose of this study was to examine falls prevalence, falls risk factors and knowledge of falls in individuals who have undergone a total hip arthroplasty. There were 135 patients examined at their one-year follow-up appointment for total hip arthroplasty. Our primary outcome, falls prevalence and falls circumstances, found a falls prevalence of 21.5% with identical circumstances to that of average community-dwelling older adults. Female sex, number of prescription medications and multiple joint replacements were found to be significantly associated with the occurrence of falls in the previous year. The Falls Risk for Older People in a Community Setting Questionnaire …

Analysis Of Subchondral Bone And Microvessels Using A Novel Vascular Perfusion Contrast Agent And Optimized Dual-Energy Computed Tomography, Justin J. Tse

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA), is a chronic debilitating disease that affects millions of individuals and is characterized by the degeneration of joint subchondral bone and cartilage. These tissue degenerations manifest as joint pain, limited range of joint motion, and overall diminished quality of life. Currently, the exact mechanism(s) and cause(s) by which OA initiates and progresses remain unknown. The multi-factorial complex nature of OA (i.e. age, diabetes, obesity, and prior injuries have all been shown to play a role in OA) contributes to the current lack of a cure or effective long-term treatment for OA.

One re-emerging and interesting hypothesis …

Liver X Receptor And Retinoid X Receptor In Cartilage Development And Homeostasis, Man-Ger Sun

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a heterogeneous and multifactorial degenerative disease characterized by cartilage degradation in the joint. Available treatment options target symptoms but do not address the underlying issue of joint tissue degeneration. A better understanding of the molecular mechanisms maintaining cartilage health is essential for developing novel therapeutic strategies. Previous studies have shown the nuclear receptor Liver X Receptor (LXR) to possess protective roles against cartilage breakdown in OA, however the underlying mechanisms behind this process remain unknown. Since LXR regulates transcription by forming obligate heterodimers with another nuclear receptor, the Retinoid X Receptor (RXR), I hypothesized that LXR and …

Pannexins 1 And 3 In Skeletal Health And Osteoarthritis, Paxton M. Moon

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a disease that gradually robs affected individuals of their mobility and places a substantial burden on health care systems and economies. OA results from pathological changes in bone, cartilage, synovium and supporting structures which are all essential to joint function. Cartilage degeneration, a hallmarking feature of OA, is an irreversible and untreatable consequence of these changes. Though the mechanisms underlying the initiation of cartilage breakdown remain unclear, joint injury and aging are risk factors. Pannexins (PANXs), a novel family of channel forming glycoproteins, have been suggested as important mediators of early OA. Therefore, my thesis tested the …

Peroxisome Proliferator Activated Receptor Delta In Osteoarthritis, Anusha Ratneswaran

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) affects 1 in 10 Canadians and is a leading cause of mobility disability worldwide. This condition is characterized by cartilage degeneration, subchondral bone damage and inflammation of the synovium, resulting in pain and joint failure. No treatments exist to stop the progression of this disease, and its underlying molecular mechanisms remain largely unknown. We previously identified the peroxisome proliferator activated receptor (PPAR) nuclear receptor pathway as altered in OA cartilage. In-vitro studies identified PPARd as a promoter of catabolic activity in chondrocytes, providing the foundation for my overarching hypothesis that PPARd inhibition is protective in OA.

I commenced …

Epidermal Growth Factor Receptor In Joint Health And Osteoarthritis, Michael A. Pest

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases in the world. Our laboratory has shown that epidermal growth factor receptor (EGFR) signalling is involved in the process of cartilage degeneration in OA. Regulation of EGFR signalling by mitogen-inducible gene 6 (Mig-6) and dual specificity phosphatase 1 (DUSP-1) allows for signal modulation, and mouse models have linked these proteins to joint pathologies. Failure to control EGFR signalling may be involved in OA progression leading to my overarching hypothesis: regulation of EGFR signalling is essential for maintenance of joint health.

I initially tested the role of Mig-6 in cartilage health …

The Association Between Soft Tissue Releases And Bony Resections Performed During Total Knee Arthroplasty And Patients' Pain And Satisfaction Postoperatively, Matt Carter

Electronic Thesis and Dissertation Repository

Total knee arthroplasty (TKA) is a surgical treatment of degenerative knee conditions such as osteoarthritis to reduce pain and increase function. Intraoperative soft tissue releases (STRs) and bony resections (BRs) are necessary for a balanced and aligned TKA. It is possible that the degree of STRs and BRs is related to final outcome following TKA and thus there may be implications for patient rehabilitation, patient expectations, pain medications, and timelines for recovery. Thus, our primary objective was to examine the association between the number of STRs and BRs performed intraoperatively and patients’ satisfaction and pain at three months. We performed …

Predictors Of Appropriate Referral To Total Knee Arthroplasty: A Validation Study, Samuel J. Malian

Electronic Thesis and Dissertation Repository

Approximately 45% of referrals from primary care physicians to arthroplasty surgeons are inappropriate. Currently, Canadians are waiting over three months for consultation with an arthroplasty surgeon. Reducing the proportion of inappropriate referrals will reduce the wait time to first consultation with an arthroplasty surgeon. This study’s objective was to validate a model that identified patient-reported predictors of appropriate referrals to arthroplasty. We screened 258 patients attending their first consultation with an arthroplasty surgeon. Participants completed the questionnaires prior to their appointment and the surgeon detailed each consultation outcome on a standardized form. We constructed our validation model using the same …

A Model To Reduce The Proportion Of Inappropriate Referrals To Surgery For Patients With Osteoarthritis: A Pilot Study, Laura K. Churchill

Electronic Thesis and Dissertation Repository

A significant proportion of patients referred for total knee arthroplasty are inappropriate candidates for surgery, which warrants remediation of the referral process to reduce wait times for the initial consult. We conducted a prospective feasibility investigation involving 166 patients referred from their general practitioner for a consultation with an orthopaedic surgeon at a joint replacement clinic. The aim of this study was to improve the validity of data collection forms and to improve the feasibility of collecting data in a clinical setting. We also wanted to strengthen our estimate of the sample size to inform the timeline. We were able …

Prehabilitation For Total Knee Arthroplasty: A Patient-Centred Approach To Maximizing Surgical Outcomes, Carly D. Mckay

Electronic Thesis and Dissertation Repository

The purpose of this dissertation was to investigate the role of prehabilitation in post-operative recovery for patients undergoing total knee arthroplasty (TKA) for osteoarthritis. Study one was a meta-analysis that aimed to consolidate the body of knowledge regarding prehabilitation for TKA patients. Study two compared the Lower Limb Tasks Questionnaire (LLTQ) to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in terms of agreement and responsiveness. Study three investigated the effect of a six-week pre-surgical strength training program on post-operative outcomes (quadriceps strength, mobility, pain, self-reported function, health-related quality of life, arthritis self efficacy) for TKA patients. Finally, study …

Investigation Of Subchondral Bone Abnormalities Associated With Osteoarthritis Using Image-Based Biomechanics, David D. Mcerlain

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is degenerative disease caused by a mechanical failure of bone and cartilage. Common risk factors for developing OA include: being over-weight, female, having joint malalignment, or a history of prior joint injury. Post-traumatic OA is extremely common in the knee as individuals frequently suffer injuries to structures that provide stability to the joint. To enhance our understanding about OA, animal models are employed where the injury can be and monitored in a controlled environment. When used in conjunction with pre-clinical imaging techniques the longitudinal degradation of bone and cartilage can be quantitatively monitored in vivo. Recent evidence …