Medicine (Northwest Academic Centre) - Theses
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ItemEvaluation of coronary stents and atherosclerosis employing optical coherence tomography and computational fluid modelling( 2017)Atherosclerotic coronary artery disease (CAD) is a major health burden worldwide and percutaneous coronary intervention (PCI) is an established treatment for this condition. Both PCI and invasive imaging techniques have evolved tremendously over the past few decades. Limitations of angiography were largely overcome, first by intra-vascular ultrasound, and then, optical coherence tomography (OCT), which is now recognized as the most sensitive and validated tool to examine the vessel lumen, plaque composition and stent-vessel wall interface. This thesis centers on randomized, OCT trials of coronary atherosclerosis and stents. In-vivo, comparative studies of drug eluting stents were conducted to directly observe their mechanical and healing characteristics. Results of these trials subsequently laid foundation for computational fluid dynamics (CFD) experiments and some illuminating observations were made around the effects of stent malapposition on intra coronary flow dynamics. It is the information of this kind that guides scientists to refine stent designs and clinicians, to improve procedural outcomes.
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ItemScreening for asymptomatic coronary heart disease in the siblings of young myocardial infarction patients (SACHSMI)( 2017)The concept of screening entails detecting subclinical disease in the hope of altering the natural progression and thereby reducing long term mortality and morbidity. For a screening program to be effective it must be targeted at a disorder that is prevalent with accepted treatments and diagnostic tools. Coronary heart disease (CHD) is ideally positioned in this respect. There are multiple strategies available to diagnose asymptomatic CHD but the emerging field of coronary computer tomography angiography (CCTA) appears to have many of the required qualities. It is non-invasive, safe and has high sensitivity to diagnose CHD. The radiation dose has markedly decreased with evolving technology and the cost is comparable to current non-invasive cardiac investigation. An effective screening strategy for CHD maybe beneficial at all ages but applying it to the young may have a greater impact on society. The aim of this thesis was to highlight the burden of CHD in the young and to asses potential screening strategies to detect asymptomatic disease. In particular the potential role of CCTA as a screening tool has been investigated. Chapters 3 and 5 discusses the results of reviews looking at the literature focusing on myocardial infarction (MI) in the young and screening for asymptomatic CHD in the young respectively. Chapter 4 discusses the findings of a study that demonstrated the prevalence of MI in the young (defined as ≤55 years) in a low socioeconomic Australian urban setting was approximately 32%. The younger patients were more likely to be male, have a family history of premature CHD and be current smokers compared to the older cohort. In general this prevalence is higher than what is reported in the literature. Chapter 6 highlights the findings of a study that used CCTA to demonstrate the prevalence of asymptomatic CHD in the siblings of young MI patients. The participants of the study were aged 30-55 and 30-60 years if males and females respectively. Obstructive CHD (defined as ≥50% stenosis of at least one epicardial coronary artery) was demonstrated in 18% of participants. All of those with obstructive CHD were either current or ex-smokers. No statistically significant association was found between traditional cardiovascular risk scores and obstructive CHD by CCTA. A similar study conducted for this research project at another healthcare centre found the prevalence of asymptomatic CHD via screening CCTA in an all comer population was 18%. Males and those over the age of 55 years were more likely to have obstructive CHD. These results are discussed in chapter 7. Compared to the published literature the prevalence of obstructive CHD by CCTA demonstrated in these two studies is higher. Screening strategies have been demonstrated to alter modifiable risks in those who participate. Chapter 8 discusses the findings of a study that demonstrated 60% of the participants of a screening program for CHD using CCTA either stopped or reduced smoking one month after undergoing CCTA. This change was largely sustained at 12 months with 55% either stopping or reducing smoking. This rate appears to be high compared to more traditional methods such as nicotine replacement therapy. For CCTA to be accepted as an effective screening modality for CHD the risks of radiation exposure need to be as low as possible. Chapter 9 discusses the results of a study comparing the radiation doses associated with three new generation CT scanners when used to perform CCTA; the Siemens Somatom Definition Flash CT scanner, the GE Revolution CT scanner and the Toshiba Aquilion ONE ViSION CT scanner. The study found all three scanners exposed subjects to below a median dose of 5 mSv, fulfilling the Australian National Health and Medical Research Council guidelines of <5 mSv for research purpose. In addition it found the Siemens Somatom Definition Flash CT scanner exposed subjects to the lowest median radiation of 1.76 mSv. This appears to suggest the new generation CT scanners expose subjects to low enough radiation for CCTA to be a viable screening modality. In summary this thesis demonstrates a high prevalence of both symptomatic CHD (in the form of MI) and asymptomatic CHD in the young. It highlights the importance of family history of premature CHD and smoking as important risk factors for the presence of asymptomatic CHD in the young as detected by CCTA. In addition asymptomatic CHD as detected by CCTA has been shown to be more prevalent in males and those over the age of 55 years. Participation in a screening program for CHD is also shown to be an effective and sustained means of modifying smoking habits. Finally the very low radiation exposure that can be achieved with the use of the latest generation of CT scanners is illustrated. In combination these findings support further research investigating the use of CCTA in a screening strategy for CHD.
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ItemThe treatment of prosthetic joint infection with debridement, prosthesis retention and biofilm-active antibiotics( 2014)Background: Prosthetic joint infection (PJI) is a serious infection that is difficult to cure and is associated with significant morbidity. The pathogenesis of PJI involves bacteria growing in biofilm adherent to the prosthesis surface, making them resistant to eradication with standard antibiotics. Recent evidence demonstrates successful treatment of early PJI with surgical debridement and retention of the prosthesis (DAR) and the biofilm-active antibiotic combination of rifampicin and a fluoroquinolone for staphylococcal infections. However, there are few studies investigating appropriate antibiotics to use in combination with rifampicin for PJI caused by staphylococci resistant to fluoroquinolones or which antibiotics to use for organisms other than staphylococci. Little is known about functional outcomes, quality of life (QOL) or complications after treatment of PJI. The aim of this thesis is to provide further evidence to help guide management in these areas. Methods: This thesis synthesizes three of my recent studies published in peer-reviewed journals and one study presented at a national scientific meeting. In the first study, outcomes were analysed for consecutive patients with staphylococcal PJI treated with DAR and a combination of rifampicin and fusidic acid. The second examined consecutive patients with a Gram-negative bacillus PJI treated with DAR and ciprofloxacin-based regimens. In the third study, consecutive patients treated for hip PJI with DAR and biofilm-active antibiotics were matched to controls that had hip arthroplasty with no infection, and their function, QOL and complications compared. In the fourth study, a large prospective hip and knee arthroplasty cohort was analysed to determine if PJI treated with DAR and biofilm-active antibiotics was predictive of adverse QOL outcomes. Results: Of 20 patients with staphylococcal PJI, treatment failure occurred in two patients. The cumulative risk of treatment failure after 1 year was 11.76% (95% CI 3.08–39.40%). Ten of 11 patients with infections involving methicillin-resistant Staphylococcus aureus had successful outcomes. Of 17 patients with Gram-negative bacillus PJI, treatment failure occurred in two patients. In only one patient was a relapsed Gram-negative infection responsible for the failure and this patient had not been treated with ciprofloxacin. The 2-year survival rate free of treatment failure was 94% (95% CI, 63–99%). In 19 hip PJI cases there was significant improvement 12-months post-arthroplasty in function according to Harris Hip Score and QOL according to the 12-item Short Form Health Survey Physical Component Summary. There was no significant difference in the improvement between 76 controls and the 19 cases. Medical complications occurred more frequently in cases than controls but the rate of surgical complications was the same. Of 2134 patients in a hip and knee arthroplasty cohort there were 37 patients with PJI treated with DAR and biofilm-active antibiotics. On multivariate logistic analysis, PJI treated this way was not predictive of adverse QOL outcomes according to SF-12 scores, however pre-arthroplasty SF-12, female gender, knee arthroplasty and a comorbidity index were. Conclusions: DAR in combination with rifampicin and fusidic acid is effective and should be considered for patients with early staphylococcal PJI, including those with infections involving fluoroquinolone-resistant organisms. DAR in combination with ciprofloxacin is effective for patients with early Gram-negative bacillus prosthetic joint infection. Treatment of PJI with DAR and biofilm-active antibiotics was well tolerated and results in good improvements in function and QOL.