Theses and Dissertations (Clinical Medicine)

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    A review of congenital heart defects in children with Trisomy 21 over a 5-year period at Charlotte Maxeke Johannesburg Academic Hospital
    (2021) Mahomed, Raeesa Moosa Kara
    Background: In the first ten years of life, mortality in Trisomy 21 (T21) is strongly associated with the presence of Congenital Heart Defects (CHDs). There is currently a lack ofl ocal and regional data regarding the prevalence, management and outcomes of children with T21 and CHDs. Objectives: To describe the prevalence, type and frequency of CHDs and revie winter ventions (cardiac catheterisation and surgery) and survival post-surgery of children with CHDs in the T21 population at a South African facility ,the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) Paediatric Cardiology Unit (PCU). Methods: A retrospective, crosssectional, observational review of 177 participants at CMJAH PCU between January 2013 to December 2017 was performed. Data collected from the PCU data base and clinical records included: demographics, echocardiographic diagnosis, details of Diagnostic Cardiac Catheterisation (DCC), Interventional Cardiac Catheterisation (ICC) and surgery required and performed, age at diagnosis and intervention as well as survival post-surgery. Results: There were 128 participants with laboratory-confirmed T21 and CHD on echocardiography meeting inclusion criteria. The majority of participants were female (56.0%) and African (97.0%). The median age at presentation was six (IQR9.75) months. The prevalence of CHDs was 77/128 (60.2%) and 58/77 (75.3%) had a single CHD. The most frequent CHD was an Atrioventricular Septal Defect (AVSD) (38) (with or without another associated CHD) .DCC was required in 60/77 (77.9%) participants and 25/60 (41.6%) were performed. The median age at DCC was 15 (IQR 15) months. One participant with isolated PDA required and under went successful ICC for PDA closure at 17 months. Surgery was required in 60/77 (77.9%) of participants, while 15/60 (25.0%) surgeries were performed. Almost half of DDCs and surgeries not performed were due to participants lost to follow up (40% and 45% respectively). The median age at first surgery was 31 (IQR 24) months. The most common surgery was an AVSD repair (73%). Post-surgery survival was 93.3% at hospital discharge, 3-week and 6-month follow-up and 86.7% at 1-year follow-up . Conclusion: The prevalence, type and frequency of CHDs in the CMJAH T 21 population is comparable to global data. The age at presentation was not optimal for early intervention, and there was further delay in catheterisation and surgery. Survival post-surgery compares favourably with other centres even though surgery was performed at a much later age than the age recommended for best outcome (sixmonths). Early screening , diagnosis and intervention can prevent morbidity, mortality due to CHDs and may decrease the financial burden on the healthcare system.
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    A radiation dose review for paediatric fluoroscopy in an Academic South African referral hospital
    (2017) Venter, Mauritz
    INTRODUCTION Children are more sensitive to radiation and it is therefore important to reduce their exposure. There are currently no published data on South African paediatric fluoroscopic upper GIT, contrasted enemas and vesico-urethrogram dosage reference levels. AIM To determine the dose area product (DAP) values in common paediatric fluoroscopic examinations: Upper GIT studies, contrasted enemas and vesico-urethrograms. The primary endpoint was comparing our median and upper third quartile DAP values to international standards. METHOD We adhere to the Radiological Society of South Africa (RSSA)/South African Society of Paediatric Imaging’s (SASPI) guidelines to minimise radiation exposure. The upper third quartile and mean DAP values were collected between March 2013 and March 2016 for each study, categorised into four age groups (0–1, 2–5, 6–10 and 11–15 years) and stratified by our three major examinations. The data were compared to literature from the National UK Radiological Protection Board. RESULTS DAP values for upper GIT studies were significantly lower in the three younger age groups. There was no significant difference in the oldest age group. DAP values for vesico-urethrograms were significantly lower in the youngest age group. There was no significant difference in the three older age groups. For our contrasted enemas, there were no suitable data for comparison. CONCLUSION By following the RSSA / SASPI guidelines, our overall DAP values compared better than the UK National Patient Dose Database in the younger age groups and no worse in the older age groups.
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    A radiation dose review for paediatric fluoroscopy in an Academic South African referral hospital
    (University of the of Witwatersrand, 2017) Venter, Mauritz
    INTRODUCTION Children are more sensitive to radiation and it is therefore important to reduce their exposure. There are currently no published data on South African paediatric fluoroscopic upper GIT, contrasted enemas and vesico-urethrogram dosage reference levels. AIM To determine the dose area product (DAP) values in common paediatric fluoroscopic examinations: Upper GIT studies, contrasted enemas and vesico-urethrograms. The primary endpoint was comparing our median and upper third quartile DAP values to international standards. METHOD We adhere to the Radiological Society of South Africa (RSSA)/South African Society of Paediatric Imaging’s (SASPI) guidelines to minimise radiation exposure. The upper third quartile and mean DAP values were collected between March 2013 and March 2016 for each study, categorised into four age groups (0–1, 2–5, 6–10 and 11–15 years) and stratified by our three major examinations. The data were compared to literature from the National UK Radiological Protection Board. RESULTS DAP values for upper GIT studies were significantly lower in the three younger age groups. There was no significant difference in the oldest age group. DAP values for vesico-urethrograms were significantly lower in the youngest age group. There was no significant difference in the three older age groups. For our contrasted enemas, there were no suitable data for comparison. CONCLUSION By following the RSSA / SASPI guidelines, our overall DAP values compared better than the UK National Patient Dose Database in the younger age groups and no worse in the older age groups.
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    A descriptive retrospective record review of paediatric patients with intracardiac thrombi associated with dilated cardiomyopathy at Chris Hani Baragwanath academic hospital
    (2016-02-09) Morar, Deksha Faye
    Intracardiac thrombi associated with dilated cardiomyopathy in paediatric patients can be a source of significant morbidity and mortality. This study looked at the prevalence, risk factors and outcomes of children complicated by intracardiac thrombi, following a diagnosis of dilated cardiomyopathy at a tertiary centre. METHODS A retrospective review of all children, between the ages of 1 and 14 years, diagnosed with dilated cardiomyopathy from August 1983 to July 2011 were assessed using the paediatric cardiology database at Chris Hani Baragwanath Academic Hospital. The study population comprised of 303 children. RESULTS The prevalence of intracardiac thrombi in the children with dilated cardiomyopathy was 13.2% (40 children). The majority were located in the left ventricle (80%). The children who developed intracardiac thrombi had a lower fractional shortening compared to the group without intracardiac thrombi (p≤0.05). 20 of these children (6.6%) had evidence of embolization (15/20 to the central nervous system). 52 of the 303 children were HIV positive (17.2%). There was no statistically significant association between HIV status and the development of intracardiac thrombi (p = 0.19). The overall mortality was 8.9%. 12 of the 27 deaths occurred in the intracardiac thrombi group showing that the children with intracardiac thrombi had a poorer outcome (p≤0.05). CONCLUSION Intracardiac thrombi is a common occurrence in paediatric patients with dilated cardiomyopathy. There is a significant relationship between the development of intracardiac thrombi and a poor fractional shortening. Patients with echocardiographic evidence of intracardiac thrombi have a worse outcome.
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    Acute coronary syndromes in black South African patients with human immunodeficiency virus infection
    (2011-10-19) Becker, Anthony Charles
    Background: South Africa is considered to be a country in epidemiologic transition with increasing rates of cardiovascular disease. In addition, it faces an HIV pandemic, with an estimated 5.5 million people infected and five hundred thousand HIV-related deaths annually. Current evidence suggests that patients infected with HIV are at a heightened risk for acute coronary syndromes (ACS) related to traditional cardiovascular risk factors, as well as factors related to the virus and its treatment (highly active anti-retroviral therapy (HAART)). HIV infection itself may independently predispose to coronary artery disease (CAD) by promoting endothelial dysfunction, a heightened pro-inflammatory state, dyslipidaemia and thrombosis, the aetiology of which is thought to be multifactoral in nature. Protease inhibitor (PI) therapy, as part of HAART, has the potential to induce an adverse metabolic phenotype, including: dyslipidaemia, insulin resistance, endothelial dysfunction and a prothrombotic state. The attributable risk of these factors in HIV-associated CAD and ACS is currently unknown, but it seems that the risk of ACS is increased by prolonged exposure to PI’s. No data currently exists on CAD in HIV patients not receiving HAART, which is problematic considering that this makes up the majority of patients in sub-Saharan Africa and that the combination of epidemiologic transition and HIV infection has the potential for greater cardiovascular morbidity, particularly with respect to atherothrombotic events. viii Aims: The aims of this thesis are twofold. Firstly, to confirm reports of epidemiologic transition in South Africa from a broad epidemiological perspective. Secondly, by focusing on treatment-naïve HIV positive black South Africans with ACS, it aims to determine differences compared to HIV negative patients with respect to demographics and risk factors, angiographic and treatment related factors as well as markers of thrombosis and inflammation with a view to providing more focused primary and secondary prevention. Methods: All the studies contained in this thesis were conducted in the Department of Cardiology, Chris Hani Baragwanath Hospital and adhere to the declaration of Helsinki. The first of the epidemiological studies, The Heart of Soweto (HOS) study (Chapter 3), was a prospectively designed registry that recorded epidemiologic data relating to the presentation, investigations and treatment of 1593 patients from Soweto with newly diagnosed cardiovascular disease during the year 2006. The second study (Chapter 4) was a cross sectional study of patients with ACS admitted to the Baragwanath coronary care unit over the year 2004 compared to the years 1975-1980. The HIV sub-study (chapters 5-8) was a prospective single centre study conducted from March 2004 to February 2008. During this time, 30 consecutive black HIV patients presenting with ACS (ACS+: HIV+ group) were enrolled. For each HIV patient with ACS, the first presenting non-HIV black patient with ACS was selected as a case control comparator (ACS+ : HIV- group). In addition, a second control group of 30 asymptomatic HIV patients, who were matched for age, sex and ethnicity (ACS- : HIV+ group), were recruited from the HIV clinic. The methodology used to compare the groups involved: clinical and demographic data collection, routine blood test evaluation, angiographic ix analysis and specific laboratory testing of various research blood parameters (including thrombotic screening and markers of inflammation and endothelial activation). Results: Chapter 3 presents the results of the large HOS study, which showed good evidence to support the theory of epidemiologic transition in Soweto. Adding to this data are the results of Chapter 4, which clearly demonstrate a substantial increase in the number of patients diagnosed with ACS at Baragwanath in recent years. Consistent with a population in epidemiologic transition, there was more than a ten-fold increase in the rate of coronary events over two decades, paralleled by increased rates of modifiable risk factors. Chapter 5 presents the clinical and angiographic data from the HIV sub-study. HIV patients with ACS were younger and had fewer traditional risk factors for CAD except for higher rates of smoking and lower HDL cholesterol levels. HIV patients had less atherosclerotic burden angiographically, but a higher thrombus burden in the infarct related arteries, suggesting a possible prothrombotic state. In addition, HIV patients had higher rates of in-stent restenosis of bare metal coronary stents at follow up. Chapters 6 and 7 present data on the thrombotic parameters between the groups, with Chapter 6 focusing mainly on coagulation pathways and Chapter 7 focusing on antiphospholipid antibodies (aPL). Chapter 8 presents data on levels of pro-inflammatory cytokines and endothelial activation markers. Greater evidence of thrombophilia was found in HIV patients with ACS as evidenced by lower Protein C (PC) levels, higher levels of Factor VIII and a higher inflammatory burden with greater degrees of endothelial cell activation - all of which increase thrombotic risk. Antiphospholipid antibodies were more prevalent in HIV patients but did not seem to be causal in the pathogenesis of thrombosis. x Conclusion: Soweto, a large, predominantly black urban area in South Africa, is in a state of epidemiologic transition, with an increasing prevalence of modifiable cardiovascular risk factors and ischaemic heart disease. Treatment-naïve HIV positive black patients presenting with ACS have different clinical and angiographic features compared to the HIV negative population. The patients are younger, more commonly male, with high rates of smoking, lower HDL levels and less atherosclerotic burden. However, there is a higher thrombotic burden, suggesting a prothrombotic state, which was evident by lower PC levels, higher factor VIII levels with a higher inflammatory burden and a greater degree of endothelial cell activation – all factors associated with a pro-atherogenic and prothrombotic state. The exact pathogenic role of HIV, independent of associated modifiable and non-modifiable risk factors, is difficult to determine, but may be important as a contributory factor in an already “vulnerable” patient. Importantly, we identified modifiable risk factors in the HIV group. Smoking may play a crucial role in the pathogenesis of ACS in these otherwise seemingly low risk patients and remains an important target for cardiovascular risk reduction. The role of HDL in the pathogenesis and prevention of HIV-associated CAD needs to be further defined, as does the role of drug eluting coronary stents in the prevention of in-stent restenosis. Cardiovascular risk assessment and appropriate primary prevention should be an important component in the management of HIV patients, regardless of treatment status. With the anticipated increase in CVD in South Africa, further research projects appropriate to the South African context will be vital in order to explore cost effective ways to provide primary and secondary prevention in order to effectively deal with the burden of epidemiological transition as well as the cardiovascular burden likely to be imposed by the HIV pandemic.