Background: Although there is a growing body of literature on the epidemiology of deliberate self-harm (DSH) in South Africa, comparatively few studies have investigated the motives for self-harm. No studies have investigated the motives for DSH in Cape Town. Aim: To identify the range of motives for DSH in Cape Town, and how these motives are associated with different sociodemographic factors, the severity of self-injury, and levels of suicidal intent. Methods: Data were collected for 238 consecutive patients presenting with DSH to the emergency department of Groote Schuur Hospital in Cape Town, South Africa. The data were analysed using bivariate and multivariate analyses. Results: Patients engaged in DSH for a range of motives. Interpersonal issues was the most common motive (70%), followed by financial concerns (22%). Male patients were twice as likely as female patients to report interpersonal motives for their self-harm. Patients who reported interpersonal issues were more likely to engage in methods of DSH that involved damage to body tissue. Patients without tertiary education were more likely to report academic concerns as a motive, and patients who reported psychiatric illness as motive for DSH were more likely to require medical interventions than those who did not. Conclusion: This study contributes novel insights into the motives for DSH in the Cape Town context and provides the foundation for continued research on the subject. The study also gives impetus to the development of therapeutic interventions focused on the motives for self-harm.

General unemployment rates are high in South Africa, but unemployment rates for persons with disabilities in the open labour market are still considerably higher than those of able-bodied persons. Research has identified a number of barriers which hinder the full inclusion of persons with disabilities in the open labour market. These barriers include poor quality education and health care, lack of sufficient accessible infrastructure and information, lack of appropriate knowledge of and access to reasonable accommodation, and attitudinal barriers in society including a narrow belief that equates disability with inability to work. On top of these barriers black persons with disabilities are further marginalised due to the historical intersectional influences of race, poverty and disability in South Africa. With a label of ‘non-productive' and dependent, persons with disabilities struggle to access the open labour market, and sustainable decent formal employment is not a reality for many persons with disabilities. Falling into the category of ‘non-productive' and dependent in a capitalist labour market excludes people not only from getting an income but also from other aspects of well-being such as active participation in one's community, and it denies people the opportunity to realise their basic human rights and human dignity. Disability Employment Support Services (DESS) provide specific supports to facilitate the employment of persons with disabilities but there is little formal knowledge in this area. Through a qualitative case study, I sought to understand why South Africa is still struggling to make real advancements for persons with disabilities in formal employment. The research question was: How are DESS provided by a disability NGO facilitating transition into formal employment for persons with disabilities in South Africa? The study included the main stakeholders as study participants, namely learners with disabilities, the DESS provider, and host employers of the DESS learners. The study site was a disability NGO in the Western Cape Province in South Africa providing DESS.

Background: In the last few decades, the increasing upsurge in HIV/AIDS and noncommunicable diseases such as heart disease, stroke and cancer as well as aging populations has given rise to the need for PC services in many countries globally, including Lesotho. However, available literature indicates gaps in PC development and integration in Lesotho. Aim: To explore the perceptions of health care workers regarding the need for PC services in three selected hospitals in Lesotho, with regards to knowledge of PC, the burden of care (especially to healthcare workers), existing PC services and policies which guide availability and access to PC medications. Objectives: (1) To explore selected health care workers' views on the burden of disease at the hospitals where they work and in Lesotho; (2) To identify knowledge, attitudes and beliefs on PC and linking that to the need for PC provision for patients diagnosed with life threatening conditions; including their families; (3) To determine which conditions in the HCWs' views qualify a patient to receive PC, and (4) To identify whether in the HCWs' views there is adequate development and provision of PC services in the hospitals where they work. Method: This study used a descriptive research design conducted within a qualitative approach. Individual semi-structured interviews were conducted with 12 research participants in three hospitals in Lesotho. Research participants included medical doctors, pharmacists, social workers and nurses. Data was recorded, transcribed verbatim and analyzed using thematic analysis. Results: Themes and sub-themes emerged from the data analysis: prevalent palliative care conditions, psycho-social support, referral criteria for palliative care services, palliative care challenges, poor infrastructure and lack of resources, accessibility and affordability of pain medication, and lack of palliative care policies and procedures. Conclusion: Although each hospital had a different pattern of views and challenges, the same reasons and issues were raised all of which suggests primarily that PC services were at low levels of operation, mostly unorganized and in many instances non-existent in Lesotho. The followings recommendations were presented: 1. Introduction of compulsory entry point education and Continuing Professional Development (CPD) for HCWs 2. Sensitization and advocacy for PC. 3. Adequate funding 4. Availability and accessibility of PC medications and 5. Policies promoting restrictions on prescriptions should be reviewed towards formulation new policies.

Background: Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in Uganda. A previous qualitative study suggested multidimensional needs. It was important to ascertain these needs and the patients' outcomes. Aims / Objectives: To determine the Palliative Care needs and outcomes of patients with Hepatocellular Carcinoma enrolled on program at Uganda Cancer Institute (UCI) and Mulago National Referral Hospital (MNRH). Methods: A longitudinal, quantitative, descriptive study was conducted from eligible in patients using convenience sampling on those who had a clinical diagnosis of HCC and were aged >18. A structured questionnaire using validated tools was administered by face to face interview at baseline then by telephone follow up at 1, 2 and 3 months. These tools include socio-demographic disease information, APCA POS and symptom assessment. Ethics approval was granted by University of Cape Town and Uganda Cancer Institute. Results: Fifty participants were recruited and among these 68% < six months' duration of illness and 74% were male. All participants were identified as stage 3 or 4 disease with 72% having an ECOG performance status 0 – 2. Fourty two percent of participants received chemotherapy and out of these 18% completed the study. Seventy-two percent of participants scored moderate to severe pain (>3/5) with a Median of (IQR) 4(3 - 5) on APCA POS and for those completed the 90 days has a Mean of ± SD 0.7±1.2. Only 34% accessed morphine and 36% accessed a specialist in PC at baseline and none at a 90 day accessed a PC specialist. Abdominal fullness and early satiety were among the common symptoms at baseline and scored in 70% of participants. At the baseline 66% expected cure, with information obtained during the study their perceptions changed. The degree of understanding of the illness at baseline scored 22%, not understanding at all was 34% hence the majority 78% at 90 days had a full understanding of the disease. While 28% felt hopeless at baseline this improved on subsequent follow-ups. Insufficient spiritual support was more marked at 90 days scored in 56% of the participants. The study showed high attrition rates >50% at 1 month) as mainly due to high mortality. Conclusions: The majority of patients were young men presenting with a late stage disease and from rural areas with significant financial constraints. There are significant unmet needs including pain, heightened existential distress and lack of clear information or goal setting which require further strengthening of PC within the medical and oncology services.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder characterised by autoantibody production and a wide spectrum of clinical manifestations. Non-scarring alopecia (hair loss) is reported to occur in up to 80% of individuals with SLE, occurring primarily in the active phase. Alopecia is also reported in up to a third of the general population, begging the question of how much diagnostic weight alopecia really has in SLE. METHODS We conducted a cross-sectional cohort study of patients with confirmed SLE, by the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, managed at the Lupus clinic at Groote Schuur Hospital, a tertiary referral hospital in Cape Town, South Africa. Age, sex and race matched controls were recruited from the Dermatology clinic at the same hospital. Participants were questioned about alopecia (‘self-reported') and examined for alopecia clinically and dermoscopically (‘confirmed alopecia'). Alopecia was classified according to the likely cause and evaluated as to whether or not it was related to SLE and to disease activity. RESULTS The study included 90 participants with SLE and 90 controls. Females predominated in the study population, with a mean age of 37.13 (range 18-69) for cases and 37.62 (range 18-72) in controls. Demographics of the 2 groups were equally matched, with two thirds (64.4%) of cases and controls self- identified as being mixed race, 33.3% as black african and 2.3% as white. Alopecia (self-reported and confirmed) was found equally in cases and control groups. In a third of the people with SLE (34, 38%) alopecia was recorded by the clinician as one of the classification criteria used by the clinician in recording the diagnosis of SLE. In 7/34 (21%) of these patients, the classification of SLE would not have been made by criteria in the absence of alopecia. Forty patients were found to have clinically apparent alopecia, 7 of these (17.5%) having diffuse alopecia. Of the remaining 33 patients with alopecia, androgenic alopecia (12/33) was the commonest form. Likewise, androgenic alopecia was the commonest type of confirmed alopecia in controls (11/33, 33.3%). Patients with self-reported alopecia had significantly higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores than people without hair loss. However, there was no statistically significant difference in SLEDAI scores between those with clinically confirmed alopecia and those with self-reported alopecia (n = 40, M = 2.88, SD = 3.35 vs n = 50, M = 2.56, SD = 3.37; t = 0.44, p = 0.660, d = 0.09). CONCLUSION Within our population the incidence of alopecia was the same in people with SLE and in controls. Hair loss was identified as androgenic alopecia in the majority of affected cases and controls. This lack of difference in type of alopecia among participants highlights the low specificity of non-scarring alopecia as a criterion for SLE and further supports the weighting of classification criteria within the various domains in the EULAR/ACR criteria.

Introduction: The South African population has a significant emergency burden of disease. In South Africa, immediate access to computed tomography (CT) imaging may not always be available. Globally, the number of all imaging studies is increasing annually. Due to access challenges patients requiring CT head imaging needs to be carefully selected to ensure safe management and discharge. Patient demographics, clinical presentation and type of expected emergency pathology known about this population will assist the emergency physician in making appropriate management decisions. Methodology: This study was conducted in two parts: a literature review and a retrospective, descriptive analysis conducted at Mitchells Plain Hospital, Cape Town, exploring the type and prevalence of pathology identified by CT head imaging in the emergency department. Data for the descriptive study was collected over a one-year period and the demographics, indications and reported pathology were described for all CT head requests in the emergency department. Statistically significant differences between groups were calculated using the Chi-squared test, depending on the sample characteristics. Statistical significance was defined as p-value <0.05. Results: There was a male predominance (57%) in this study with the most common comorbidity being hypertension. The cumulative yield of pathology was identified at 58% on imaging (new pathology 40% and existing pathology 18%). Stroke (32%), trauma (30%) and seizures (16%) were the most common indications for imaging with a yield per indication of 54%, 48% and 20% respectively. The most common imaging finding across all categories was an ischaemic stroke. Stroke indicated CT head imaging pathology demonstrated ischaemic (19%) to haemorrhagic (3%) stroke pathology. The most common finding on a trauma indicated CT head was an ischaemic stroke (13%). Seizure indicated CT head imaging demonstrated 18% with new pathology and 36%that had existing pathology. Emergency imaging was performed on average under seven hours post consultation. Conclusion: Acquiring CT head imaging in a resource limited setting requires appropriate clinical history, examination as well as awareness of the most prevalent pathology of the community the doctor is treating. Even though yield of pathology was considered high when compared to HIC there was similarity in yield to local and international LMICs. Stroke, trauma and seizures are common indications for imaging in the South African setting with the most common pathology identified to be an ischaemic stroke.

Background At least a quarter of patients admitted to the Cardiac Intensive Care Unit (CICU) will develop Acute Kidney Injury (AKI) and some of these patients receive Renal Replacement Therapy (RRT). The clinical profiles and outcomes of CICU patients receiving RRT in resource constraint settings like South Africa is unknown. Objectives The objectives of this study were to determine the clinical profiles and outcomes of patients receiving RRT in the CICU in a South African Tertiary Centre. Methods In this retrospective study we included consecutive patients admitted and receiving RRT at the Groote Schuur Hospital CICU from 01/01/2012 to 31/12/2016. Results During the study period 3247 patients were admitted to the CICU and 46 received RRT. The RRT patients had a mean (SD) age of 52 (17) years, 56% were males, and 65% had a background history of systemic hypertension. Heart failure syndromes accounted for 60.9% of CICU admission in the RRT patient group, followed by acute coronary syndromes and arrhythmias, which accounted for 26.1% and 13.0% respectively. The RRT patient population had an in-hospital and 30-day mortality of 58.7% and 60.9% respectively. Baseline use of Angiotensin Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) was associated with a reduced 30 day mortality, Hazards Ratio (HR) 0.43; 95% Confidence interval (95%CI) 0.20 – 0.93; p = 0.031. In addition, heart failure was associated with an increased 30 day mortality, HR 2.52; 95% CI 1.10 – 5.78; p = 0.029. Conclusion Heart failure syndrome accounts for a majority of RRT patients admitted to the our CICU. Patients receiving RRT in CICU have a high in-hospital and 30-day mortality.

Neural crest cells are a unique feature of vertebrates. This embryonic cell population is multipotent, giving rise to many structures including peripheral neurons. The sea lamprey, Petromyzon marinus, is at the base of the vertebrate lineage and offers an ideal model for the ancestral neural crest. Comparisons to the modern neural crest gene regulatory network (GRN) such as that of the chicken can elucidate essential conserved regions of the GRN. Previous studies in P. marinus revealed a neural crest-specific enhancer for the neural crest specification gene, SoxE1, which showed conserved activity in chicken and zebrafish neural crest. Here, the SoxE1 enhancer was subdivided to find the core active region, using enhancer-reporter assays in chicken and lamprey. Additionally, the segments were analysed for putative transcription factor binding sites, which were mutated. The central 610 bp of the SoxE1 enhancer retained its activity in lamprey and chicken neural crest. Mutation of a putative Sox10 and Tfap2 binding sites within the core enhancer did not result in complete loss of enhancer activity in the chicken or lamprey, however the number of positive embryos was reduced in the lamprey. Further subdivision of the SoxE1 enhancer core region revealed the 3' half drives expression in the branchial arches of the chicken embryo. Neural crest specific-reporter activity was confirmed by immunological staining embryo sections with the reporter gene overlapping with neuronal and endogenous Sox10 expression. The identified core region of the SoxE1 enhancer shows a conserved regulatory mechanism in vertebrates. Future work will interrogate how this enhancer region interacts directly with neural crest GRN members. In addition, preliminary single cell RNA-seq analysis of dissected dorsal neural tube tissue from the lamprey embryos revealed a neural crest specific cell population that expressed key neural crest specification marker genes. This data can reveal previously unknown genes involved in the neural crest GRN as well as identifying novel cell types during development.

Background The number of people with type 2 diabetes mellitus (T2DM) is increasing rapidly in Africa, straining already overstretched health systems. The association between hyperglycaemia first detected in pregnancy (HFDP), which includes both diabetes mellitus in pregnancy (DIP) and gestational diabetes mellitus (GDM), and the later development of T2DM and cardiovascular disease risk in the mothers and possibly overweight in their children is well recognised. This thesis contributes to the largely unexplored body of work on the prevalence of T2DM and CVD risk factors in African women after HFDP and the relationship between HFDP and childhood overweight and obesity. The thesis investigated: 1) the prevalence of T2DM and impaired glucose metabolism in African women of childbearing age; 2) the prevalence of T2DM and cardiovascular disease risk factors in women within 6 years after HFDP, and 3) the influence of maternal blood glucose levels during pregnancy and overweight and obesity in the offspring at the preschool age. Methods A systematic review and meta-analysis of all studies published from January 2000 to 2017 was carried out to estimate the prevalence of T2DM and impaired glucose regulation states. In the PROgression to Diabetes study (PRO2D), women diagnosed with GDM using the 2008 National Institute for Health and Care Excellence (NICE) criteria during 2010 and 2011 at a major referral hospital and their offspring were reviewed up to 6 years later. Relevant maternal and foetal/neonatal data were routinely collected during pregnancy and birth. The women were recalled for an assessment of T2DM (OGTT and HbA1C) and other cardiovascular risk factors (insulin resistance, dysglycaemia, dyslipidaemia and obesity) and their offspring for overweight/obesity. The women were reclassified into DIP and GDM using the WHO 2013 criteria for the diagnosis of HFDP. The pooled prevalence of T2DM was; 7.2% (95% CI 5.6% to 8.9%), impaired fasting glycaemia, 6.0% (95% CI 4.2% to 8.2%) IGT, 0.9% to 37.0% from 39 studies in 27 African countries, and 53 075 participants. The response rate for the PRO2D was 44.2% (final sample n=220). At follow up, almost half of the women, [48% (95% CI 41.2–54.4)], had T2DM, 83% in the DIP subtype and 31% with GDM had T2DM. The type of treatment [insulin (OR 25.8, 95% CI 3.9–171.4, p = 0.001), oral antidiabetic drugs (OR 4.1, 95% CI 1.3–12.9, p = 0.018)], fasting glucose(OR 2.7, 95% CI 1.5–4.8, p = 0.001), OGTT 2-hour glucose (OR 4.3, 95% CI 2.4–7.7, p < 0.001), during pregnancy; current anthropometry [waist circumference (OR 1.1, 95% CI 1.0–1.1, p = 0.007), hip circumference (OR 0.9, 95% CI 0.8–1.0, p = 0.001), BMI (OR 1.1, 95% CI 1.0–1.3, p = 0.001)]) were associated with T2DM. The prevalence of CVD risk factors was: insulin resistance 75% (95%CI 65.9-82.3), dyslipidaemia 74.6% (95%CI 68.3- 79.9), dysglycaemia 62.3% (95%CI 55.6-68.5), and raised blood pressure 41.4% (95%CI 35.0-48.0) and metabolic syndrome 60.9% (95%CI 54.3- 67.2). Of the 443 neonates exposed to HFDP during pregnancy, almost one-third [29.6% (95%CI 25.5 – 34.0)] were large-for-gestational-age (LGA) at birth and just over a fifth [21% (95%CI 15.4 – 27.8)] were either overweight or obese at preschool age. A strong association was found between maternal fasting glucose at HFDP diagnosis and birth weight zscore (OR 1.11, 95%CI 1 -1.22, p=0.046), maternal postprandial 2-hour glucose during the third trimester and weight z-score at birth (OR 1.23, 95%CI: 1.07 - 1.42, p = 0.005) and at preschool age (OR 1.37, 95%CI: 1.03 - 1.81, p = 0.031). Conclusion The high prevalence of T2DM and CVD risk factors in relatively young women and overweight and obesity in their offspring within 6 years of the index pregnancy demonstrates the need for context-specific interventions to prevent HFDP, to optimise screening for HFDP and to reduce cardiometabolic disease risk in the postpartum period.

Hypertension is a major worldwide predictor of morbidity and mortality. The search for genes that contribute to blood pressure is ongoing. The epithelial sodium channel genes were implicated when the beta subunit (SCNN1B, gene ID 6338) was found to have a mutation that caused Liddle's syndrome. The R563Q mutation in the beta subunit has been associated with hypertension and pre-eclampsia in the Xhosa and Coloured people in Cape Town. The thesis consists of a cross-sectional analysis of the prevalence of the R563Q mutation in multiple ethnic groups in South Africa and a longitudinal functional assessment in response to saline infusion. The objectives were to determine the prevalence of the R563Q mutation and association with hypertension, and if it persists within families; to speculate as to the origins of the mutation; to determine if there were any relevant clinical differences between comparable patients with essential hypertension; to determine if the mutation predicted a difference in response to acute sodium loading and if a physiological difference is observed in sodium channel activity when expressed in oocytes. 8 A high frequency of hypertensives in Johannesburg and Cape Town were found to be heterozygous and the mutation associated with hypertension, including within families. In the Khoisan the R563Q mutation was found at a high frequency (19%) in a random sample, suggesting the mutation originated from this population. The saline challenge illustrated the in vivo effects of the mutation. The results suggest that the sodium channel is innately overactive in heterozygous subjects and that counter-regulatory mechanisms are in place to compensate for changes in renal sodium handling. However, preliminary in vitro testing in oocytes did not show a difference in sodium channel activity. Conclusion: This thesis has shown that the R563Q mutation is found in multiple ethnic groups in South Africa, in which it associates with hypertension; and possibly originated from the Khoisan. In vivo effects are described. The results are important because hypertension resulting from the R563Q mutation is a common and treatable cause of hypertension. It is recommended that hypertension units in South Africa screen for the mutation and alter treatment appropriately. A further recommendation is that a sodium channel inhibitor, such as amiloride, in an appropriate form, is registered in South Africa for the treatment of hypertension.