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Item 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 KaraBackground: 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.Item Acute coronary syndromes in black South African patients with human immunodeficiency virus infection(2011-10-19) Becker, Anthony CharlesBackground: 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.Item Alloplastic Total Temporomandibular Joint Reconstruction A 10Year Experience of the University of the Witwatersrand JohannesburgRisimati Rikhotso; Mmathabo SekhotoItem Botulinum neurotoxin injections in essential infantile esotropiaa comparative study with surgery in largeangle deviationsIsmail Mayet; Naseer Ally; Hassan Alli; Mohammed Tikly; Susan WilliamsItem A brief history of South Africa's response to Aids(2014) Simelela, N.P.; Venter, W.D.F.The story of the AIDS response in South Africa over the past 4 years is one of great progress after almost a decade of complex and tragic denialism that united the world and civil society in a way not seen since the opposition to apartheid. Today the country can boast >2 million people on antiretroviral therapy, far and away the largest number in the world. Prevention efforts appear to be yielding results. The estimated number of annual new HIV infections declined by 79 000 between 2011 and 2012. New HIV infections among adults aged 15 - 49 years are projected to decline by 48% by 2016, from 414 000 (2010) to ~215 000 (2016). The national incidence rate has reached its lowest level since the disease was first declared an epidemic in 1992, translating into reductions in both infant and under-5 mortality and an increase in life expectancy from 56 to 60 years over the period 2009 - 2011 alone. This is largely thanks to a civil society movement that was prepared to pose a rights-based challenge to a governing party in denial, and to brave health officials, politicians and clinicians working in a hostile system to bring about change.Item The challenges of managing breast cancer in the developing world- a perspective from sub- Saharan Africa(2014-05) Edge, J; Buccimazza, I; Cubasch, H; et al.Communicable diseases are the major cause of mortality in lower-income countries. Consequently, local and international resources are channelled mainly into addressing the impact of these conditions. HIV, however, is being successfully treated, people are living longer, and disease patterns are changing. As populations age, the incidence of cancer inevitably increases. The World Health Organization has predicted a dramatic increase in global cancer cases during the next 15 years, the majority of which will occur in low- and middle-income countries. Cancer treatment is expensive and complex and in the developing world 5% of global cancer funds are spent on 70% of cancer cases. This paper reviews the challenges of managing breast cancer in the developing world, using sub-Saharan Africa as a model.Item Charting the path along the continuum of PMCT or HIV-1 to elimination and finally to eradication(2014-01) EditorialIn this editorial we traverse the continuum of transmission of HIV-1 from mothers to children to highlight the biomedical history of this problem. Treatment has progressed from prevention with antiretrovirals (ARVs) through to a broader set of interventions, including various breastfeeding options and other health system improvements, that have increased the possibility of eliminating mother-to-child-transmission (MTCT) of HIV.Item Clients experiences utilizng a safer conception service for HIV affected individuals implications for differentiated care service delivery modelsSheree Schwartz; Natasha Davies; Nicolette Naidoo; Diantha Pillay; Nokuthula Makhoba; Saiqa MullickItem Clinical access to Bedaquiline Programme for the treatment of drug-resistant tuberculosis(2014-03) Conradie, F; Meintjies, G; Hughes, J; et alWhile clinical disease caused by drug-sensitive Mycobacterium tuberculosis (MTB) can usually be treated successfully, clinical disease caused by drug-insensitive MTB is associated with a poorer prognosis. In December 2012, a new drug, bedaquiline, was approved by the US Food and Drug Administration. This article documents the process whereby the National Department of Health, Right to Care and Médecins Sans Frontières obtained access to this medication for South Africans who might benefit from subsequent implementation of the Clinical Access to Bedaquiline Programme.Item Clinicopathological characteristics among South African women with breast cancer receiving antiretroviral therapy for HIVBoitumelo Phakathi; Herbert Cubasch; Sarah Nietz; Caroline Dickens; Therese Dix-Peek; Maureen Joffe; A Neugut; J Jacobson; Raquel Duarte; Paul RuffItem Congenital Rubella Syndrome Surveillance in South Africa using a sentinel site approach A crosssectional studyNkengafac Villyen Motaze; Jack Manamela; Sheilagh Smit; Helena Rabie; Gary Reubenson; Daynia Ballot; David Moore; E et al; Cheryl Cohen; Melinda SuchardItem The cost of harmful alcohol use in South Africa(2014-02) Matzopoulos, R G; Truen, S; Bowman, B; et al.Background. The economic, social and health costs associated with alcohol-related harms are important measures with which to inform alcohol management policies and laws. This analysis builds on previous cost estimates for South Africa. Methods. We reviewed existing international best-practice costing frameworks to provide the costing definitions and dimensions. We sourced data from South African costing literature or, if unavailable, estimated costs using socio-economic and health data from secondary sources. Care was taken to avoid possible causes of cost overestimation, in particular double counting and, as far as possible, second-round effects of alcohol abuse. Results. The combined total tangible and intangible costs of alcohol harm to the economy were estimated at 10 - 12% of the 2009 gross domestic product (GDP). The tangible financial cost of harmful alcohol use alone was estimated at R37.9 billion, or 1.6% of the 2009 GDP. Discussion. The costs of alcohol-related harms provide a substantial counterbalance to the economic benefits highlighted by the alcohol industry to counter stricter regulation. Curtailing these costs by regulatory and policy interventions contributes directly and indirectly to social well-being and the economy. Conclusions. Existing frameworks that guide the regulation and distribution of alcohol frequently focus on maximising the contribution of the alcohol sector to the economy, but should also take into account the associated economic, social and health costs. Current interventions do not systematically address the most important causes of harm from alcohol, and need to be informed by reliable evidence of the ongoing costs of alcohol-related harms.Item 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 FayeIntracardiac 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.Item Determinants of poor adherence to antiretroviral treatment using a combined effect of age and education among human immunodeficiency virus infected young adults attending care at letaba hospital hiv clinic Limpopo Province South AfricaK Mabunda; E Ngamasana; Joseph Babalola; M Zunza; Peter NyasuluItem Effect of seasonal variation on the peak presentation of slipped capital femoral epiphysis A comparison of children in Johannesburg South Africa and London UKGregory Firth; Matthew Foster; Carl Pieterse; Yammesh Ramguthy; Alane Izu; Joseph Bacarese-Hamilton; Manoj RamachandranItem Epidemiology of maxillofacial fractures at two maxillofacial units in South Africa(South African Dental Association, 2018-04) Mogajane, Brampie; Mabongo, MzubanziThis article compares epidemiologic characteristics of maxillofacial fractures seen in patients presenting at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) with those seen at Polokwane – Mankweng Hospital Complex (PMHC).Item Equity in maternal health outcomes in a middleincome urban setting a cohort studyA De Groot; L Van de Munt; D Boateng; A Savitri; Kerstin Klipstein-Grobusch; E et alItem Evidence for use of a healthy relationships assessment tool in the CHARISMA pilot studyElizabeth E. Tolley; Andres Martinez; Seth Zissette; Thesla Palanee-Philips; Florence Mathebula; Siyanda Tenza; Miriam Hartmann; et al et al