Back pain is a massive global public health problem with multiple contributing factors including obesity. Obesity is thought to be linked to back pain through mechanical factors. However, obesity also causes a systemic low-grade inflammatory milieu. This would suggest a possible biochemical link between obesity, intervertebral disc degeneration, and back pain. Furthermore, the relationship between obesity and the clinical presentation of spine patients is unclear. This thesis aims to examine the effect of and relationship between obesity, the intervertebral discs, and back pain from biochemical, clinical, and epidemiological perspectives. In this thesis, an in vitro study assessed the effect of leptin, a fat-specific cytokine, upon the intervertebral disc. The bovine intervertebral disc was used as a model in a cell culture system. An ex vivo study examined leptin and pro-inflammatory cytokines produced by paraspinal adipose tissue taken during routine surgical procedures from spinal patients. Plasma taken from patients presenting with low back pain was analysed by mass spectrometry and multiplex immunoassay to identify possible protein biomarkers. At an epidemiological level, statistical modelling of the Genodisc patient population was conducted. This was a pan-European study of 2636 patients presenting to tertiary spinal units. Analyses were performed to examine relationships between obesity, quantified by body mass index (BMI), and pain, clinical diagnosis, and spinal degeneration identified on magnetic resonance imaging (MRI). Leptin was shown to increase the production of and expression of degradative and pain-generating molecules by disc cells. A pro-inflammatory environment, especially IL-6, potentiated this response. Leptin and pro-inflammatory cytokines produced by paraspinal fat were unrelated to clinical symptoms. However, levels of the pro-inflammatory cytokines, TNF-α and IL-6, were raised in the plasma of patients with greater pain or those with spinal stenosis. Furthermore, clusterin and complement were identified, by mass spectrometry, as potential biomarkers for spine patients. Epidemiological analyses revealed that obesity was associated with greater back pain, although the magnitude of this association was small. Similarly, obesity was associated with a diagnosis of spinal stenosis. Finally, increased BMI was found to be an independent predictor of disc degeneration, spinal stenosis, and disc herniation on MRI. In summary, this thesis has furthered the clinical understanding of lumbar spine pathology and back pain. It will provide clinicians with a better framework to assess spine patients. These results show that obesity is associated with lumbar spine degeneration and pain. Leptin could be a factor mediating this relationship. Further studies should concentrate on clarifying the mechanism of action of leptin upon the intervertebral disc and assessing the longitudinal effect of obesity upon the lumbar spine. In this thesis, an in vitro study assessed the effect of leptin, a fat-specific cytokine, upon the intervertebral disc. The bovine intervertebral disc was used as a model in a cell culture system. An ex vivo study examined leptin and pro-inflammatory cytokines produced by paraspinal adipose tissue taken during routine surgical procedures from spinal patients. Plasma taken from patients presenting with low back pain was analysed by mass spectrometry and multiplex immunoassay to identify possible protein biomarkers. At an epidemiological level, statistical modelling of the Genodisc patient population was conducted. This was a pan-European study of 2636 patients presenting to tertiary spinal units. Analyses were performed to examine relationships between obesity, quantified by body mass index (BMI), and pain, clinical diagnosis, and spinal degeneration identified on magnetic resonance imaging (MRI). Leptin was shown to increase the production of and expression of degradative and pain-generating molecules by disc cells. A pro-inflammatory environment, especially IL-6, potentiated this response. Leptin and pro-inflammatory cytokines produced by paraspinal fat were unrelated to clinical symptoms. However, levels of the pro-inflammatory cytokines, TNF-α and IL-6, were raised in the plasma of patients with greater pain or those with spinal stenosis. Furthermore, clusterin and complement were identified, by mass spectrometry, as potential biomarkers for spine patients. Epidemiological analyses revealed that obesity was associated with greater back pain, although the magnitude of this association was small. Similarly, obesity was associated with a diagnosis of spinal stenosis. Finally, increased BMI was found to be an independent predictor of disc degeneration, spinal stenosis, and disc herniation on MRI. In summary, this thesis has furthered the clinical understanding of lumbar spine pathology and back pain. It will provide clinicians with a better framework to assess spine patients. These results show that obesity is associated with lumbar spine degeneration and pain. Leptin could be a factor mediating this relationship. Further studies should concentrate on clarifying the mechanism of action of leptin upon the intervertebral disc and assessing the longitudinal effect of obesity upon the lumbar spine.

Made available in DSpace on 2016-08-10T10:53:35Z (GMT). No. of bitstreams: 1 LUCIANO LUCINDO DA SILVA.pdf: 762537 bytes, checksum: fc611b5b537940fa8236781a4cf03333 (MD5) Previous issue date: 2012-03-20 / OBJECTIVE: To analyze, based on scientific literature, the cost of infection related to health care (IRAS) in orthopaedic surgery. METHODS: We conducted a study of integrative review of publications on infection in orthopaedic surgery from January 1990 to December 2011. Sixteen papers were considered in its entirety. The indexing databases were used to search PubMed and the Latin American and Caribbean Health Sciences (LILACS). RESULTS: We found in the databases searched 21,490 publications on cost of infections, considering several sites and etiologies. Only 16 of these articles refer to the cost of surgical site infection in orthopaedic. The surgical sites were most commonly studied hip and knee, making a total of 14 publications. The infection rate in knee arthroplasty is 0.92%, while the hip is 0.88%. The growing cost of surgical site infection in orthopaedic is 1.5 to five times and the hospitalization may represent more than half of these costs. Mortality increases in cases of infection related to large procedures, reaching a rate of 15.4% in hip surgery. CONCLUSIONS: Infection in orthopaedic surgery increases the length of stay, mortality and costs. Patients undergoing arthroplasty have higher costs. Pathogens resistant to antimicrobial have higher costs when compared to infections by sensitive germs. / OBJETIVO: Analisar, com base na literatura científica, o custo das infecções relacionadas à assistência à saúde (IRAS) em cirurgias ortopédicas. METODOLOGIA: Foi realizado um estudo de revisão integrativa de publicações sobre infecção em cirurgia ortopédica no período de janeiro de 1990 a dezembro de 2011. Foram considerados 16 artigos científicos. As bases indexadoras utilizadas para pesquisa foram PubMed e Literatura Latino- Americana e do Caribe em Ciências da Saúde (LILACS). RESULTADOS: Foram encontrados nas bases de dados pesquisadas 21.490 publicações sobre custo de infecções, considerando vários sítios e etiologias. Desses somente 16 artigos referem-se a custo de infecção em sítio cirúrgico ortopédico. Os sítios cirúrgicos mais comumente estudados foram quadril e joelho, perfazendo um total de 14 publicações. A taxa de infecção em artroplastia de joelho é de 0,92%, ao passo que no quadril é de 0,88%. O aumento do custo da infecção em sítio cirúrgico ortopédico é de 1,5 a cinco vezes, em que a hospitalização pode representar mais da metade desses custos. A mortalidade aumenta nos casos de infecção relacionada a procedimentos de grande porte, podendo chegar a uma taxa de 15,4% nas cirurgias de quadril. CONCLUSÕES: Infecção em cirurgia ortopédica aumenta o tempo de internação, mortalidade e custos. Pacientes submetidos a artroplastias cursam com maiores gastos. Patógenos resistentes aos antimicrobianos geram maior custo quando comparado a infecções por germes sensíveis.

Nitric oxide is a small free radical generated by family of enzymes, the nitric oxide synthases. In a series of experiments performed over the last 15 years we showed that nitric oxide is induced by all three isoforms of nitric oxide synthase during tendon healing and that it plays a crucial beneficial role in restoring tendon function. In normal tendon we found very little nitric oxide synthase activity while in injured rat and human tendons nitric oxide synthase activity was expressed in healing fibroblasts in a temporal fashion. In healing rat Achilles tendon fibroblasts the first isoform to be expressed was endothelial nitric oxide synthase (eNOS), followed by inducible nitric oxide synthase (iNOS), and then brain or neuronal nitric oxide synthase (bNOS). Systemic inhibition of nitric oxide synthase activity decreased the cross sectional area and mechanical properties of the healing rodent Achilles tendons. Addition of nitric oxide via NO-flurbiprofen or NO-paracetamol enhanced rat Achilles tendon healing. Addition of nitric oxide to cultured human tendon cells via chemical means and via adenoviral transfection enhanced collagen synthesis, suggesting that one mechanism for the beneficial of nitric oxide on tendon healing might be via matrix synthesis. The final part of the work involved three randomized, double-blind clinical trials which evaluated the efficacy of nitric oxide donation via a patch in the management of the tendinopathy. In all three clinical trials there was a significant positive beneficial effect of nitric oxide donation to the clinical symptoms and function of patients with Achilles tendinopathy, tennis elbow and Achilles tendonitis.

There have been many advances in surgical residency education and similar interest exists in fellowship education. This study evaluated perceptions among spine surgeons about the specific competencies required for successful spine surgical fellowship training, and then compared these perceptions to clinical practice. Firstly, a questionnaire was administered to spine fellow trainees and academic spine surgeons across Canada in order to identify the cognitive and technical skills required for successful spine fellowship training. Fellowship trainees and supervisors had similar perceptions on the relative importance of specific cognitive and technical competencies. Differences in perceptions were found when comparing surgeons based on background residency specialty training (orthopaedic surgical or neurosurgical). Secondly, using administrative data, a retrospective study assessed volumes, surgeon characteristics, and outcomes for surgery of the degenerative lumbar spine in Ontario between 1995 and 2001. Neurosurgeons were found to perform more decompressions, and more total procedures, than orthopaedic surgeons with similar outcomes.

There have been many advances in surgical residency education and similar interest exists in fellowship education. This study evaluated perceptions among spine surgeons about the specific competencies required for successful spine surgical fellowship training, and then compared these perceptions to clinical practice. Firstly, a questionnaire was administered to spine fellow trainees and academic spine surgeons across Canada in order to identify the cognitive and technical skills required for successful spine fellowship training. Fellowship trainees and supervisors had similar perceptions on the relative importance of specific cognitive and technical competencies. Differences in perceptions were found when comparing surgeons based on background residency specialty training (orthopaedic surgical or neurosurgical). Secondly, using administrative data, a retrospective study assessed volumes, surgeon characteristics, and outcomes for surgery of the degenerative lumbar spine in Ontario between 1995 and 2001. Neurosurgeons were found to perform more decompressions, and more total procedures, than orthopaedic surgeons with similar outcomes.

Abstract can be viewed in PDF document. / Thesis (Ph.D)-University of KwaZulu-Natal, Durban, 2008.

The aim of this thesis was to establish the long-term outcomes of the Oxford medial Unicompartmental Knee Arthroplasty (OUKA), define patient selection criteria and to develop and externally validate an evidence based method of patient selection for this procedure. In the hands of the developer surgeons, outcomes following medial OUKA were found to be good with an implant survival of 94% (95%CI 92 to 96) at ten-years and 91% (95%CI 83 to 98) at fifteen-years. Across the published literature, however, variation in outcomes was observed with a meta-analysis of published series of OUKA finding estimates of ten-year survival ranging from 57% to 100%, mean 88% (95%CI 85 to 90). It was identified that both increased surgical caseload (volume) and increased surgical usage (proportion of primary knee arthroplasty that are OUKA), a surrogate marker of indications, were associated with improved outcomes. Surgical usage, however, was more important, with good results following OUKA seen with high surgical usage, representing broad indications, independent of the surgical volume. This finding, coupled with differences in patient demographics and failure mechanisms between usage groups, highlighted that differences in indications for OUKA may explain the variability in outcomes observed. One reason surgeons may have a low usage is if they apply previously recommended patient factor contraindications based on age (<60 years), weight (≥82kg) and activity level (high activity). When disease factors are standardised, however, it was found that patients with these previously reported contraindications often actually did better than those without, and outcomes of knees implanted where all these factors were present were as good as where none were present. Therefore, the decision to proceed with OUKA should be based on the pathoanatomy of disease. Optimal candidates for OUKA should have full-thickness cartilage loss, with bone on bone arthritis, in the medial compartment, as knees with partial thickness cartilage loss were found to have worse functional outcomes and almost three-times the reoperation rate, predominantly for unexplained pain. Provided there was full-thickness preserved cartilage laterally and functionally normal ligaments, the presence of lateral osteophytes and the macroscopic status of the anterior cruciate ligament was not found to influence outcomes, nor did the presence of patellofemoral joint disease (with the exception of lateral facet disease with bone loss and grooving) or anterior knee pain. The pathoanatomy of disease can be identified radiologically, however, standing knee radiograph were found to perform poorly. To identify medial compartment full-thickness cartilage loss either a varus stress radiograph or fixed flexion radiograph, both at 20° flexion and aligned to the joint surface, were identified as the optimum views. To confirm preserved lateral compartment full-thickness cartilage a valgus stress radiograph at 20° flexion, aligned to the joint surface, was identified as the most appropriate technique. As stress radiographs are time and resource consuming, a novel stress device was developed in line with the IDEAL-D framework and validated against the gold standard of manual, clinician performed stress radiographs, as well as independently tested in clinical practice. Finally, to simplify patient selection, an atlas based Decision Aid, combined with a structured radiographic assessment, was developed and externally validated with an accuracy of over 90% at identifying suitability for OUKA. The routine use of this approach would be expected to standardise patient selection and ultimately translate into improved long-term outcomes.

Includes bibliographical references / Background: Dislocation is one of the most common orthopaedic complications after primary total hip arthroplasty (THA). The reported dislocation rate in elective THR is 5 - 8%. This number increases up to 22% for THA done for neck of femur fractures. Larger femoral head sizes increase the head-neck ratio and range of motion before impingement, therefore reducing the dislocation rate. Due to the reported increase in dislocation for trauma, some surgeons prefer to do a hemi-arthroplasty or open reduction and internal fixation (ORIF). Methods: A retrospective review of all THA done for neck of femur fractures during 2006 - 2012 was undertaken at a large referral hospital. Records were reviewed for patient related and surgical risk factors. We excluded all pathological fractures, extra-capsular fractures and failed ORIF. Results: A total of 96 cases were identified as suitable for analysis. Average age at surgery was 73.2 years (range 30 - 81). Delay to surgery was 5.3 days (range 1 - 63). Average follow up period was 18.3 months (range 3 months - 4.3years). Four patients (4.3%) had a confirmed dislocation. The four patients who had confirmed dislocation had the following characteristics, 28 mm femoral head size, age over 60 years, 2 posterior approaches and 3 females, although not statistically significant. Conclusion: The outcomes of THR in patients with neck of femur fractures can be favourable and provide good long-term prosthesis survival. We report on low dislocation rate post total hip replacement for intra-capsular neck of femur fractures.

The overarching theme of this thesis is to discuss the research to date on intimate partner violence (IPV) in orthopaedic surgery and to begin to study selected issues that have been understudied in orthopaedic surgery and IPV. This thesis outlines the current state of knowledge in the field of IPV and orthopaedic surgery and provides some insight into three selected “emerging issues” in the field which warrant future research including: education of orthopaedic surgeons and residents to reduce barriers and improve perceptions; IPV perpetrators; and outcomes for victims of IPV. The findings demonstrate that a short course on IPV for orthopaedic trainees led to an improvement and retention of knowledge three months after the course. IPV education should be integrated into training programs for orthopaedic surgeons. Our systematic review on IPV perpetrator factors indicates that using alcohol or drugs, experiencing child abuse, witnessing interparental aggression, low socioeconomic status, and psychological conditions like depression and anxiety were commonly associated with IPV perpetration. Perpetrator treatment programs should take into consideration modifiable and preventable factors that are associated with IPV perpetration. This thesis proposes a pilot prospective cohort study as the first step toward determining how experiences of IPV affect orthopaedic outcomes such as injury-related complications. The proposed study will determine feasibility and assist in the development a larger-scale multinational prospective cohort study that will engage health care professionals from around the world to increase awareness of how IPV affects patients’ musculoskeletal outcomes. In the past decade, the field of orthopaedic surgery has become more aware of the issue of IPV, but there are many questions that remain. Future research into the above issues will be an excellent first step to fully understanding the issue of IPV in orthopaedic patients, and may lead to improved support of victims of IPV in the future. / Thesis / Master of Science (MSc)

Symptomatic spinal disorders affect a large proportion of the population and are associated with substantial morbidity, social burden, and economic impact. Spine surgery interventions can provide excellent results in carefully selected patients whose symptoms fail to improve with non-operative management, but an evidence-based approach is paramount to optimize outcomes and rigorous standards of health research methodology are critical to avoid misleading conclusions. This thesis aimed to investigate and apply modern innovations in health research methodology to the field of spine surgery. It consists of seven chapters divided between three sections: randomized controlled trials, observational studies, and systematic reviews and meta-analyses. By applying the findings of each chapter, clinicians, researchers, and other evidence users can advance the credibility of future research and enhance the care of patients with spinal disorders. / Thesis / Doctor of Philosophy (PhD)