On a daily basis critically ill paediatric patients are admitted in the Paediatric Critical Care Unit (PCCU). Some of these paediatric patients require cardiothoracic surgery and is mechanically ventilated post-operatively. Chapter one of this study gives an orientation to this research and explains that in order to prevent ventilator associated complications and high hospitalisation costs, the mechanically ventilated paediatric patient following cardiothoracic surgery should be extubated as soon as he/she is ready. Chapter two is dedicated to the available literature on this topic and indicates that literature on extubation criteria for the mechanically ventilated paediatric patient is minimal. The methodology of this study is discussed in detail in Chapter three. Chapter four gives a detailed explanation of the research findings and the researcher included the developed clinical pathway for the extubation of the paediatric patient following cardiothoracic surgery in a private hospital in Gauteng. The relevant clinical pathway functions as a guideline and evidence-based tool in the PCCU. Lastly Chapter five gives a summary of this study and a few recommendations are made. The researcher has included a personal reflection in this Chapter. / Dissertation (MCur)--University of Pretoria, 2014. / tm2015 / Nursing Science / MCur / Unrestricted

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Ischaemic heart disease (IHD) is the leading cause of death worldwide. Currently, even optimal medical therapies do not attenuate deterioration of the left ventricular (LV) function completely. Stem cell therapies, and recently cardiac stem cell therapies, have emerged as potential novel treatments for IHD. However, clinical evidence from randomised controlled studies has shown mixed results. Thus understanding what patient-related factors may affect the therapeutic performance of the cells may help improving treatment outcomes. The studies described in this thesis aim to understand how cardiac progenitor cells (CPCs) can re-vascularise ischaemic myocardium and promote functional repair of the heart. Resident CPCs were isolated and expanded from the right atrial appendage of 68 patients following the ‘cardiosphere’ method (cardiosphere-derived cells or CDCs). They resemble mesenchymal progenitors as they lack the expression of endothelial and haematopoietic cell surface markers but express mesenchymal progenitor cell markers (e.g. CD105, CD90). Cell function was evaluated by support of angiogenesis, mesenchymal lineage differentiation potential in vitro, and improvement in heart function in vivo. Notably in vitro, CDC from different patients differed in their angiogenic supportive and differentiation potentials. In a rodent model of myocardial infarction (MI), transplantation of CDC reduced infarct size significantly (p<0.05). However, only those CDCs with a robust pro-angiogenic ability in vitro improved vessel density and heart systolic function (p<0.05) in vivo. A multiple regression model, which accounted for 51% of the variability observed, identified New York Heart Association (NYHA) class, smoking, hypertension, type of ischaemic disease and diseased vessel as independent predictors of angiogenesis. In addition, gene expression analyses revealed that differential gene expression of several extracellular matrix components (e.g. CUX1, COL1A2, BMP1 genes and microRNA-29b) could explain the differences observed in CDC’s vascular supportive function. In summary, this is the first description of variability in the pro-angiogenic and differentiation potential of CDCs and its correlation with their therapeutic potential. This study indicates that patient stratification may need to be included in the design of future trials to improve the efficacy of cell-based therapies.

Vascular disease is the leading cause of death and disability worldwide. Incidence, risk factors, and outcome of coronary artery disease have been extensively studied, but there are fewer data on other forms of arterial disease, including carotid, aortic, visceral, and peripheral arterial disease. Although the burden of these diseases may be increasing due to the ageing population, we lack the most basic epidemiological data on which to base clinical decisions on individual patients (short and long-term prognosis); local service provision (current incidence and projected future burden); public health / screening initiatives (age and sex-specific incidence, risk factors, and outcome); and with which to assess current levels of primary prevention (pre-morbid risk factor control). Indeed, it is this lack of data, rather than a lack of treatments that is the greatest barrier to effective prevention. I have contributed to, cleaned, and analysed data from the Oxford Vascular Study, a prospective, population-based study (n=92,728) of all acute vascular events (2002-2012), and the Oxford Plaque Study, a carotid atherosclerosis biobank of over 1000 carotid plaques, in order to study these conditions. For acute aortic disease, I aimed to assess the risk factors associated with acute abdominal aortic aneurysms (AAA) and the population impact of the current UK AAA screening programme; and the incidence, risk factors, outcome, and projected future burden of acute aortic dissection. For acute peripheral arterial disease, I assessed the risk factors associated with premature onset and poor outcome, together with current levels of primary prevention. For symptomatic carotid artery disease, I studied the timing and benefits of surgical intervention in the current era; and went on to assess whether underlying carotid plaque morphology can be used to improve stroke risk stratification and help explain why ocular and cerebral stroke types have vast differences in future ipsilateral stroke risk. I found that compared with the current UK AAA screening strategy (one-off scan for men aged 65), screening of male smokers at 65 and all men at 75 would prevent nearly four-times as many deaths and three-times as many life-years lost with 21% fewer annual scans. I have also shown that incidence of acute aortic dissection is higher than previous estimates, a third of cases are out-of-hospital deaths, and uncontrolled hypertension is the most significant treatable risk factor for this condition. For acute peripheral arterial disease, the presence of multiple atherosclerotic risk factors are associated with premature onset, and severity of ischaemia, pre-morbid renal dysfunction, cardiac failure, and diabetes mellitus are predictive of future limb loss and survival. A significant proportion of acute peripheral events are AF-related in high risk patients who were not pre-morbidly anticoagulated despite having no contraindications and being at low risk of bleeding. Symptomatic carotid artery disease currently accounts for <10% of incident cerebrovascular events, and only 40% of these patients undergo surgical intervention. Due to improvements in medical therapy and on-going delays to intervention, little benefit is currently obtained from intervening in patients with <70% stenosis. Ipsilateral stroke risk is correlated with several carotid plaque features in a time-dependent manner, confirming the potential utility of plaque morphology in risk stratification. In addition, plaques from patients with cerebral events were significantly more unstable and inflammatory than from those with ocular events, helping explain differences in stroke risk between these groups. My findings advance the understanding of these conditions that form the backbone of modern vascular surgical practice, and I hope will improve prevention, clinical management, and outcome for patients with vascular disease.