Electronic Theses and Dissertations (Masters)

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Micro-architecture of the human postnatal maxilla in relation to tooth development and eruption
(University of the Witwatersrand, Johannesburg, 2024) Mhlathi, Xolisiwe; Hutchinson, Erin; Small, Candice
The growth, modeling and remodeling of the maxilla are shaped by the biomechanical forces exerted on it. As functional demands of the masticatory system become more complex due to dental development and eruption, the intensity and complexity of the biomechanical forces increases and as such influences the associated bony micro-architecture. The knowledge gained from assessing the impact of these changes on the micro-architecture of the maxilla is important in the clinical and forensic contexts. Thus, this study aimed to assess changes in the micro- architecture of the alveolar region of postnatal and sub-adult human maxilla in relation to dental development and eruption. The study sample included seventy-nine individuals, subdivided into three groups according to dental development stages: deciduous dentition (n = 28; 0-5 years), mixed dentition (n = 9; 6-12 years), and permanent dentition (n = 42; 13-18 years). Maxillae were scanned using micro-computed tomography. Seven regions were selected along the buccal, lingual, and the apical surfaces of each dental crypt for evaluation of micro-architecture, which included bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular spacing (TbSp), material surface to material volume (BS/BV), and trabecular number (TbN). The micro-architecture of the maxilla changed from a more porous to a less porous nature, following patterns of bone remodeling during growth. These changes included an increase in BV/TV while BS/BV and TbN both significantly decreased. Thus, the trabeculae became more mineralized and decreased in number as they thickened. No significant differences were observed in TbTh and TbSp between the dentition groups. The observed micro-architecture reflects changes in the state of the dentition as well as adjustments to the complex functional environment of the oral cavity complex
Is it fair to limit access to free human papillomavirus vaccinations to only girls in public schools in South Africa?
(University of the Witwatersrand, Johannesburg, 2024) Scheepers, Vanessa Christina
Gender-neutral Human Papillomavirus (HPV) vaccination programs, covering girls and boys, are necessary to combat the global rise in HPV-related cancers and escalating treatment costs. HPV vaccination is the primary preventative intervention for both men and women. In South Africa, it is freely available to adolescent girls in public schools, excluding girls in private schools and boys. This exclusion deprives them of the benefits of free HPV vaccination, potentially exposing them to a greater risk of cancer, and incurring more costs to society in the end. I apply Kantian ethics and rule utilitarianism to evaluate and argue that the current South African school-based HPV program is unfair and morally unjustified in limiting free access to HPV vaccination to only girls in public schools. I specifically examine Kant’s Formula of Humanity and the Formula of Universal Law to evaluate the ethical dimensions of the policy and show that the policy has significant shortcomings in terms of equality, autonomy, and universality from a Kantian perspective. I further demonstrate that a policy excluding certain groups based on gender and socio-economic status is not aligned with the principles of rule utilitarianism because it fails to maximise overall well-being, perpetuates inequalities, hinders optimal vaccine coverage, and neglects the potential benefits of gender-neutral vaccination. I address potential counterarguments that proponents of the current policy might present from both a Kantian and a utilitarian viewpoint. I advocate for a more just and ethical approach and recommend a revision of the HPV vaccination policy to align with Kantian and utilitarian principles. I show that both Kantian ethics and rule utilitarianism support a gender-neutral HPV vaccination strategy in the South African context. Gender- neutral coverage of HPV vaccination ensures free and equitable access to all adolescents who can benefit from it, irrespective of sex, gender, school type, or socio-economic circumstances. A gender-neutral approach to HPV vaccination is more aligned with the South African Constitution
Do governments have any prima facie duties to fund influenza vaccination (for the elderly in sa) and adults 65 years and above to vaccinate against influenza, respectively?
(University of the Witwatersrand, Johannesburg, 2023) Sarangarajan, Ruach; Ewuoso, Cornelius
In this dissertation, I draw on the thinking about solidarity, reciprocity, distributive justice, incompleteness and conviviality grounded in African philosophy broadly, including African ethics, African epistemology, African aesthetics, African metaphysics and African logic, to name a few, to argue that institutions, particularly the South African (SA) government, have a prima facie responsibility to fund the influenza vaccination for adults 65 years and above. Equally, I draw on the moral norms arising from the same values grounded in African philosophy to argue that adults 65 years old have a prima facie duty to vaccinate against influenza. These claims address three core issues relevant to fostering influenza vaccine access: availability, affordability and acceptability. While the former claim ensures that influenza vaccinations are affordable and available to the target population group, the latter underscores the obligation of adults 65 years and above to vaccinate to address acceptability issues. Although the dissertation focuses specifically on the South African government to defend its core thesis, I believe the arguments can reasonably be adapted to address the responsibilities of other African governments and older persons in other regions. Notably, these responsibilities are that the SA government should make influenza vaccines freely available for adults 65 years and above in public and private health facilities, provided financial allocation and their extant relationships allow for this. Additionally, the SA government has a responsibility to improve influenza vaccine procurement and availability in the country, preferably through increasing manufacturing capabilities. Furthermore, the dissertation argues that adults 65 years and above have a prima facie responsibility to vaccinate against influenza. Notably, adults 65 years and above have a duty of conviviality to act in ways that limit harm to them and others. This project is intrinsically valuable to promote epistemic justice, thereby contributing towards the decolonization of the global healthcare system. Moreover, this project has social significance in contributing to mitigation efforts against future public health challenges associated with population ageing in resource-limited developing African nations, wherein the impact of population transition will be most felt
Postmortem modifications of skeletal elements caused by common small southern African scavenging mammals found in a peri-urban environment
(University of the Witwatersrand, Johannesburg, 2024) Da Costa, Roxanne Rebelo; Keyes, Craig Adam
The definition of taphonomy is everchanging and has been adapted from the original use to explain fossilization of animal remains to aiding in forensic investigations. Forensic taphonomy has helped estimate postmortem interval timelines and aid in understanding what happened to a body postmortem. A taphonomic variable of interest is animal scavenging. Animal scavenging can hinder forensic investigations through the alteration or deletion of evidence and the scattering of remains. The aim of the study was to describe the nature of postmortem modifications of skeletal elements caused by common small scavenging animals found in peri-urban environments in southern Africa. Understanding scavenging and scattering patterns of common animals found in a peri-urban environment in South Africa can aid in locating skeletal elements in forensic investigations. In this study, bovine skeletal elements were scattered at the National Zoological Gardens in Pretoria, in the enclosures of genets, servals, a warthog, and suricates. The elements remained in the enclosures for a week, after which they were collected, and the process was replicated three times. The samples were then macerated, analysed, and photographed at the Johannesburg Forensic Pathology Services. Scores were the most commonly observed postmortem modifications caused by all species studied and they were mainly superficial, indicating they were more likely caused by claws rather than the teeth of the animal. A chi-square test was conducted to test whether an association existed between the location on the skeletal element scavenged and the scavenging species. The statistic proved that there was an association and that each scavenging species studied have a preference for specific locations and skeletal elements that they scavenge on. A scoring system was developed to describe the intensity of modifications inflicted on the skeletal elements. The Cohen’s Kappa coefficient showed that the scoring method produced reliable scores. This is the first forensic taphonomic study to describe the modifications caused by genets, servals, and suricates. The results of the study can assist forensic anthropologists in the assessment of postmortem taphonomic alterations to skeletal elements in peri-urban environments in Southern Africa.
Should commercial surrogacy be permissible in South Africa?
(University of the Witwatersrand, Johannesburg, 2024) Jafta, Nonhlanhla Angel; Ewuoso, Cornelius
This dissertation is mostly a conceptual or normative project arguing that commercial surrogacy should be permissible in South Africa. I defend this claim using African-inspired principlism, emphasising principles of respect for persons and living in harmonious relationships. This is achieved through valuing relationships within communities and respecting people by respecting their autonomous decision-making capacities. It is also achieved by recognising the interconnectedness of people and that a person is a person through other people, which is called Ubuntu
Epistemic (in)justice, social identity and the Black Box problem in patient care
(University of the Witwatersrand, Johannesburg, 2024) Khan, Muneerah; Ewuoso, Cornelius
This research report draws on (for the first time) the moral norms arising from the nuanced accounts of epistemic (in)justice in the work of decolonial scholars, and social identity in the work of relational autonomists to defend the thesis that using AI in patient care in light of the Black Box problem is deeply problematic and is ethically impermissible. This does not necessarily doom AI since it may be used for other purposes within the healthcare system. The report highlights what needs to happen to align AI with the moral norms it draws on. Deeper thinking – from backgrounds other than decolonial scholarship and relational autonomy – about the impact of AI on the human experience needs to be done to appreciate any other barriers that may exist. Future studies can take up this task.
Design and synthesis of a nanocapsule system for transdermal delivery of lignocaine across the skin
(University of the Witwatersrand, Johannesburg, 2024) Makha, Lerato Mathabelo; Choonara, Yahya E.; Ubanako, Philemon; Makhathini, Sifiso
Pain is a major health problem that is caused by an emotional and sensory experience due to injury of tissues and can be differentiated as acute or chronic. Pain protects humans by assisting in making us aware that there is body injury or potentially damaging situations. If acute pain is not treated correctly, it can lead to chronic pain. Pain can be treated by several classes of medications including analgesics, Non-steroidal Anti-inflammatory drugs (NSAIDs), opioids, anti-depressants, and local anaesthetics. These medicines are administered orally. Although this is the preferred route of administration, it has many inherent limitations that can negatively impact the drug's desired pharmacological effects. Since the skin is the most convenient and accessible region for medication administration, innovative delivery techniques like Transdermal Drug Delivery Systems (TDDS) have been developed to circumvent the drawbacks of traditional drug delivery routes. This method has displayed fewer side effects experienced with conventional oral medications like gastric irritation and first-pass hepatic metabolism causing low blood concentration of the drug leading to low therapeutic effect. Nonetheless, the stratum corneum (SC), the skin's outermost layer, functions as a strong barrier to prevent most medications from penetrating the skin. Much attention has been paid to the use of nanocarriers as a transdermal delivery system of different accessible pharmaceuticals through the SC with the potential to have local or systemic effects to treat various disorders (Alexander et al., 2012). The purpose of this report was to synthesize Lignocaine (LIG)-loaded nanocapsules to evaluate their potential to transport LIG across the skin for increased effectiveness and fewer side effects. Lignocaine-loaded nanocapsules (LIG-PLGA-PC) were prepared by employing the solvent displacement technique. Aqueous phase consisted of 200 mg of Tween® 80 in 30 ml of purified water. The mixture was ultrasonicated for few minutes then put under electronic magnetic agitation. Organic phase was prepared by dissolving 125 mg of PLGA, 250 mg of PC and 30 mg of LIG in 5 ml of chloroform. Under probe sonication, organic phase was added drop wise to the aqueous phase and was allowed to stir overnight to remove the organic solvent. The formulated nanosystem was then frozen and lyophilized (FreeZone® 2,5, Labconco®, Kansas City, MS, USA) at -80 °C for 48 hours to yield a powder and analyzed using different analytical techniques. Four samples were prepared with three samples having a drug loaded in the organic phase. The fourth sample was blank, without the drug in the organic phase. The synthesised nanoparticles were characterized using Scanning Electron Microscopy (SEM), zetasizer, Ultraviolet (UV) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and Thermogravimetric Analysis (TGA). SEM clarified the configuration of the surface and shape of the nanocapsules by beaming electrons that interacted with the sample's atoms to produce three-dimensional surface topography. Using the zeta-sizer, the size of nanoparticles was found to be around 139.8 nm and a polydispersity index (PDI) of 0.182 a while the zeta potential was -48,2 mV. A drug entrapment efficacy (DEE) percentage of 72 % was achieved. LIG release studies showed a sustained release over a 24-hour period. The FTIR spectral evaluation of drug loaded sample showed a vibration at 3000–2800 cm−1 indicating a N-H stretch, and 1750-1735 cm−1 presented with a C=O stretching group. At 1250–1020 cm−1 there is a C-N stretching confirming the presence of an amine group. Thermogravimetric Analysis (TGA) thermal studies indicated that the LIG nanoparticulate structure increased the thermal stability of LIG. To investigate the biocompatibility of the nanoformulation, immortalized human keratinocytes (HaCaT) were treated with LIG-PLGA-PC copolymeric nanocapsules and an MTT (3-(4,5- dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay was conducted to evaluate the cytotoxicity of the treatments. Absorbance values were measured at 570 nm employing a Thermo Lab systems Multiskan MK3 microplate reader. From the cytotoxicity study conducted, at 48-hour, LIG-PLGA-PC nano formulation showed increased cell viability of 102, 103, and 110 % for 6,25 μg/ml, 3,125 μg/ml, 1,5625 μg/ml concentrations respectively. The blank nanocapsule showed a cell viability of 99, 98 and 100 % at concentrations of 6,25 μg/ml, 3,125 μg/ml, and 1,5625 μg/ml. The HaCaT cell micrographs showed cell proliferation on the drug loaded as well as plain drug figures. This can be confirmed by the MTT assay that the nanoformulation was non-cytotoxic with predicted biocompatibility. The combined experiments and findings of the LIG-PLGA-PC nanocapsule synthesis demonstrated that further studies and investigations are required to show that these nanoparticles can be used as a possible formulation for TDDS medication delivery of LIG for pain treatment.
The moral obligation to include pregnant women in clinical trials
(University of the Witwatersrand, Johannesburg, 2024) Ramtahal, Kieara-Lee; Behrens, Kevin
Many pregnancies are complicated by serious medical conditions that require treatment, and despite the need to use medication during pregnancy, the majority of clinical trials do not include the pregnant population, which leaves pregnant women with limited “robust” data regarding the safety and effectiveness of medications that they may require during pregnancy (Little & Wickremsinhe, 2017, p.1). In this report, I examine the reasons provided for the exclusion of pregnant women from clinical trials and the ethical reasons for their inclusion. I argue that, 1. the exclusion of pregnant women as participants in clinical trials could potentially expose future pregnant women to significant harms, 2. the benefits arising out of the inclusion of pregnant women in clinical trials far exceeds the possible harms to the pregnant women trial participants and their fetuses and 3. pregnant women deserve fair access to research trials where their participation will involve access to potential benefits. I also discuss objections to my arguments and provide a response. In conclusion, I contend that pregnant women should be included in clinical trials unless there are compelling reasons for exclusion.
Mechanisms of cell death induced by betulinic acid and dihydroartemisinin polymer-drug conjugates on pancreatic cancer cells
(University of the Witwatersrand, Johannesburg, 2023) Moisane, Karabo Sekopi
Introduction: Pancreatic cancer (PC) is a lethal malignancy characterised by a poor response to standard chemotherapy. Like other cancers, PC employs apoptosis evasion mechanisms to ensure tumour survival. This makes apoptosis evasion an important cancer hallmark that can be targeted for effective treatment. Betulinic acid (BA) and Dihydroartemisinin (DHA) have shown promising anticancer properties via induction of apoptosis; however, limitations such as poor aqueous solubility and high molecular weights limit their overall therapeutic effect. Polymer drug conjugation is a promising solution. This project aimed to confirm the cytotoxic potential and determine the mechanism of cell death induced by BA and DHA polymer-drug conjugates on pancreatic cancer cells. Methodology: The cytotoxic effect of the free drugs, BA and DHA, and the complimentary conjugates on Vero (non-cancerous cells) and MIA PaCa-2 pancreatic cancer cells was confirmed using tetrazolium salt assays. The antioxidant potential and effect of reactive oxygen species (ROS) activity were conducted using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and N, N-Dimethyl-p-phenylenediamine (DEPPD) assays. The mode of cell death and the effect of the drugs on the cycling characteristics of the cells were determined using flow cytometric assays. Their effect on the expression of proapoptotic genes was assessed using real-time polymerase chain reaction (PCR). The apoptosis evasion mechanism of the pancreatic cancer cells was determined using the human nuclear factor kappa-B p65 subunit (NF-κB/p65) enzyme-linked immunosorbent assay (ELISA) kit. Results: The conjugates PEG-BA and PEG-DHA demonstrated lower IC50 values compared to the free compounds BA and DHA with a selectivity index of 3.00 and 1.61 for the conjugates, and 1.12 and 1.71 for BA and DHA, respectively. Antioxidant analysis showed that the free drugs, BA and DHA, had a weak antioxidant potential with IC50 values of more than 100 μM while the conjugates resulted in lower IC50. PEG-BA (4 μM) induced higher apoptosis than free BA (53.07% vs 7.68%) on the MIA PaCa-2 cells. Furthermore, PEG- DHA resulted in 50.99% of the MIA PaCa-2 cells undergoing apoptosis compared to free DHA (12.90%). Both conjugates induced low levels of necrosis (< 1%). After treatment with PEG-BA, the MIA PaCa-2 cells underwent a dose-dependent Sub-G1 arrest, which further indicated apoptosis. Similarly, PEG-DHA also induced a Sub-G1 arrest in addition to G2/M arrest on the MIA PaCa-2 cells. Compared to the free BA, PEG-BA treatment resulted in the highest overexpression of the following proapoptotic genes: TNF, BAX, CASPASE 3, CASPASE 2 and CASPASE 8. Both BA and PEG-BA induced a moderate increase in the concentration of NF-κB compared to the untreated MIA PaCa-2 cells. Conclusion: This study confirmed that conjugation of the polymer PEG to natural compounds with anticancer properties, such as BA, further improves the apoptosis-inducing ability against pancreatic cancer cells with the overexpression of proapoptotic genes, necessitating further exploration
A retrospective study of the epidemiology, management and outcomes of patients with dialysis-requiring acute kidney injury, over a 24-month period, at Helen Joseph Hospital, Johannesburg, South Africa
(University of the Witwatersrand, Johannesburg, 2024) Naidu, Yashika
Background Dialysis-requiring acute kidney injury (AKI) carries significant morbidity and mortality. A cohort of patients was reviewed at Helen Joseph Hospital (HJH) to contribute to local knowledge on the epidemiology, referral patterns, and outcome of dialysis-requiring AKI. Methods A retrospective review was conducted of patients receiving dialysis for AKI at HJH between 1 January 2019 and 31 December 2020. Patient demographics and aetiologies of AKI were described. Effects of baseline characteristics and aetiology of AKI on patient survival, duration of hospitalisation, and renal function recovery were analysed using Cox proportional hazards modelling and binomial regression analyses. Results Dialysis-requiring AKI occurred in younger median age. Human immunodeficiency virus (HIV) infection (38.7%), hypertension (27.4%) and diabetes mellitus (12.3%) were common comorbidities. Community-acquired AKI predominated with significant renal dysfunction at presentation. Leading causes of AKI were sepsis (51.9%) and hypovolaemia (26.4%). Mortality was high (56.6%). Age and diabetes increased mortality and reduced renal recovery. Sepsis (HR 1.48, 95% CI 1.37–1.60, P < 0.001) and cardiorenal syndrome (CRS) type 1 (HR 1.78, 95% CI (1.57–2.01, P < 0.001) increased mortality. HIV infection did not increase the risk of mortality and showed an increased likelihood of renal recovery (OR 1.71, 95% CI 1.51–1.95, P < 0.001). Chronic kidney disease was prevalent in survivors. Conclusion Results resemble that of other low- and middle-income countries. People living with HIV may be at increased risk of dialysis-requiring AKI. AKI carries a high mortality rate. Sepsis and CRS carry an increased risk of death; sepsis-associated AKI and comorbid diabetes are associated with reduced odds of renal recovery to dialysis-free levels.
Characteristics and Outcomes of HIV-infected Children on Antiretroviral Therapy referred for Vitological failure
(University of the Witwatersrand, Johannesburg, 2024) Magomani, Xitshembiso Confidence; Sipambo, Nosisa
Background: The advent of Anti-Retroviral Therapy (ART) has substantially improved virological outcomes for individuals globally living with Human Immunodeficiency Virus. However, the rates of virological suppression in children and adolescents continue to lag behind those observed in adults. Objectives: This study aims to describe the characteristics and outcomes of children on ART referred to Hariet Shezi Children’s Clinic, Chris Hani Baragwanath Academic Hospital for virological failure. Additionally, the research seeks to identify factors associated with virological failure in this specific population. Methods: Conducted as a retrospective review, this study examined the records of children living with HIV aged 0-14 years, referred to Hariet Shezi Children’s Clinic, for management of virological failure between 01 January 2010 and 31 December 2019. Results: Among the 105 patients meeting the inclusion criteria, the median age at referral was 11 years (IQR 6.7-13 years), with 51.4% being male. Significant proportions (37.3%) of patients above the age of 8 were unaware of their HIV status. At referral, 35.2% were on a Non-nucleoside reverse transcriptase inhibitor-based regimen, and 82% had a VL log 10 exceeding 4. Notably, 86.5% of those on NNRTI were switched to a second-line regimen, compared to 4.4% on Protease inhibitor- based regimens. Despite differences in interventions, virological outcomes were similar at 6 ±3 months. Approximately 56.2% of patients received adherence counselling in conjunction with other interventions, indicating that virological failure in the majority resulted from sub-optimal adherence and additional factors. A significant reduction in median viral load was observed at 6 ±3 months and 12±3 months post-intervention (P <0.001). Conclusion: Viral suppression remains a challenge in the paediatric and adolescent populations. Addressing this challenge necessitates a multifaceted approach involving various interventions. Greater resource allocation towards the optimization of viral suppression rates in children and adolescents living with HIV is imperative
A Review of the Use of CT Pulmonary Angiography in Pregnant and Postpartum Patients at an Academic Centre
(University of the Witwatersrand, Johannesburg, 2024) Herbst, Wilhelm; Zamparini, Jarrod; Moodley, Halvani; Bhoora, Shastra
The most common cause of maternal death during pregnancy and the puerperium in developed countries is venous thromboembolic events, including pulmonary embolism (PE).1 The risk for venous thromboembolism (VTE) is significantly increased during pregnancy and the postpartum period, as these patients are in a state of hypercoagulability, are prone to venous stasis and may have superimposed endothelial damage.2 Data has shown that women have a 5-fold increased risk of developing VTE during pregnancy, as compared to their non-pregnant counterparts,3 and, according to a Scottish study, the incidence of antenatal VTE has increased over the last 26 years.4 Past research has observed an incidence of PE in pregnant or postpartum women of 3 in 10,0002,5, with one death in every 100,000 deliveries.6 Some studies have found an absolute incidence of VTE in pregnancy to be as high as 1 to 2 cases per 1000 pregnancies3; a risk that is nearly five times higher than that among non-pregnant women.7 More than half the cases of VTE in pregnancy occur in the first trimester, before 20 weeks’ gestation.5 Yet, 80% of VTE cases in the postpartum period have been observed to occur within the first 3 weeks following delivery.8 Recent studies haveM revealed a raised relative risk (however low absolute risk) that remains up to 12 weeks following delivery.9 A large meta-analysis and systematic review of seventeen studies, which included 25,339 patients, found that 2% of patients presenting to the emergency department with symptoms suggestive of PE, were pregnant.10 This translates to a 12.4% positivity rate for VTE in nonpregnant patients, compared with 4.1% in pregnant patients.10 The perceived lower yield of confirmed VTE in pregnancy can be ascribed to the low threshold physicians have to scan pregnant patients, due to the high risk of devastating sequelae of PE in pregnancy
Anticoagulation For Nonvalvular Atrial Fibrillation In South Africa
(University of the Witwatersrand, Johannesburg, 2024) Mogashoa, Vanessa; Tsabedze, Nqoba; Mpanya, Dineo
Background: Nonvalvular Atrial fibrillation (NVAF) is a growing epidemic in Africa. Anticoagulation, considered the backbone of NVAF management, is limited to warfarin as the mainstay of available anticoagulation therapy in most low-and-middle-income countries (LMICs). The optimal time in the therapeutic range (TTR) while on warfarin is crucial to avoid bleeding and thromboembolic complications. This study aimed to assess anticoagulation control in patients with NVAF on warfarin in Johannesburg, South Africa. Methods: We conducted a cross-sectional retrospective study on consecutive patients with NVAF managed between the 1st of January 2015 and the 31st of December 2019 at a tertiary- level academic centre in Johannesburg, South Africa. Anticoagulation control for patients with NVAF was assessed by calculating the time in therapeutic range using the Rosendaal method. Results: The study population comprised of 177 patients diagnosed with NVAF. The mean age in the study population was 65.0 ± 13.1 years. The median TTR among patients with NVAF was 46% [interquartile range (IQR): 8.7 – 86.0], and 63 (35.6%) patients with NVAF had a TTR ≥ 70%. Patients with poor anticoagulation control (TTR<70%) were on warfarin for a shorter duration compared with those with optimal anticoagulation control [56 days (IQR: 43 – 84) vs 70 days (IQR: 56 – 140), p=0.0013]. The mean CHA2DS2-VASc score was 4 ± 1.5, and it did not differ between patients with poor or optimal anticoagulation control. Among the 175 patients with calculable HAS-BLED scores, 21 (12.0%), 112 (64.0%) and 42 (24.0%) were at a low, moderate, and high risk for bleeding, respectively. Of the 21 patients in the HAS BLED low risk category, only 4 (19.0%) had a TTR<70% (p<0.001). Warfarin toxicity was documented in 13 (7.3%) patients. Conclusion: In our study, a TTR ≥ 70%, suggesting poor anticoagulation control was found in 35.6% of NVAF patients on warfarin. Larger multicentre trials comparing the occurrence of bleeding, thromboembolic events, as well as the total cost to the healthcare system in patients treated with warfarin compared to direct oral anticoagulation therapy are required to guide oral anticoagulation strategies in Africa
Virological response in children and adolescents switching to dolutegravir based regimens in Johannesburg, South Africa – A Longitudinal Cohort Study
(University of the Witwatersrand, Johannesburg, 2023) Mafora, Tshiamo; Technau, Karl
Introduction: Dolutegravir (DTG) was introduced into South African HIV management guidelines in November 2019, and has since been the mainstay of both adult and paediatric first line antiretroviral treatment (ART) regimens. Following its rapid and widespread introduction we assessed the rate of virological suppression over two years in paediatric patients switching to DTG as part of first line treatment. Methods: We performed a retrospective cohort study at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. Children and adolescents already on first line ART who switched to DTG (between November 2019 and November 2021) were included. Baseline characteristics (at DTG switch) included age, weight, gender, viral load (VL), CD4, and pre-switch regimen. Past ART exposure and past viraemic periods (years VL >1000 copies/ml) were assessed and VL suppression rates (< 50 copies/ml) were calculated at 6, 12 and 24 months post-switch. Associations with non-suppression were assessed using uni- and multivariate analysis. Results: Of the 747 participants that were switched to DTG, 724 (97%) qualified for a VL and 697 (96%) of those had at least one VL done after switch. Overall, 83% (450/543) were suppressed at 6 months, 86% (434/504) at 12, 91% (487/534) at 24 months. Overall, at a median of 637 days after switch, 90% (624/697) were suppressed at their last VL. Factors associated with not being suppressed at the last VL included: missing a follow-up visit by more than 90 days post-switch to DTG (OR: 3.2 [CI:1.5-6.8], p=0.003), switching to DTG with a VL of 50-1000 rather than <50 copies/ml (OR 2.0 [CI:1.1-3.9], p=0.042), having the blood test done during July December (OR 2.0 [CI:1.2-3.4], p=0.011), and having had exposure to viraemia ≥1000 copies/ml for more than two years between first ART start and DTG switch (OR: 1.9 [CI: 0.9-3.7], p=0.071). Conclusion: In our population, similar to other studies, VL suppression was effectively maintained in the majority of patients after switching to DTG. The switch did however result in a loss of suppression in some patients and caution is needed in children and adolescents with missed visits and extensive prior viraemia
Clinicopathological spectrum of cutaneous malignancies at the skin tumour clinic, charlotte Maxeke Johannesburg academic hospital in Johannesburg, South Africa: a 5-year retrospective review
(University of the Witwatersrand, Johannesburg, 2023) Gwinji, Tapiwa Munyaradzi; Modi, Deepak
Background Skin cancer is the most common malignancy in South Africa, incidence of which continues to rise. This disease remains a consistent problem in South Africa due to a multifactorial risk complex arising mainly from the high levels of year-round Ultraviolet (UV) exposure, high burden of HIV and late health seeking behaviour leading to poly-etiological skin cancers. Despite the ever-present danger that is cancer, the data and literature surrounding skin cancers among different races and ethnic groups remains inadequate as there are few population-based cancer registries in South Africa and only histologically confirmed cancers are logged into the national cancer registry. Objectives To describe the nature, extent and demographic characteristics of patients with histologically confirmed skin cancer seen at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) multidisciplinary skin cancer clinic during the period of January 2015 to December 2019 and to add to the body of literature concerning skin cancers in South Africa. Methods A retrospective chart review identified all patients who were managed for histologically confirmed malignant skin tumours at CMJAH skin tumour clinic. Types, quantity and distribution of common invasive malignancies by population group, age, gender, anatomical site and risk factor were explored. Result A total number of 531 participants with histologically confirmed skin cancers were identified. The most common malignancies were Kaposi’s sarcoma(KS) (53.2%), squamous cell carcinoma (SCC) (27.0%), basal cell carcinoma (BCC) (10.4%), cutaneous melanoma (CM) (7.4%) and mycosis fungoides (MF) (4.2%). SCC and AIDS-associated KS were the most common skin cancer in the white and black population respectively. Conclusion This study provides valuable scientific data on the distribution and patient demographics of skin cancer in the public health system in Johannesburg, South Africa, on which further research can be based. This study highlights the burden of HIV associated skin cancer in this region. There is a need for further research and equitable appropriation of resources and public health awareness efforts towards strengthening UV and HIV-related skin cancer prevention initiatives in SA.
Awareness Factors Affecting Contraceptive Uptake in women attending the Gynaecology Out-Patients Department, at a Tertiary Hospital
(University of the Witwatersrand, Johannesburg, 2023) Ndlovu, Sinegugu
Objectives: The objectives of the study were to assess the knowledge and awareness of contraception in the women seen at Chris Hani Baragwanath Academic Hospital Gynaecology Out-patient department. We also looked at the efficiency of contraceptive counselling from the health care providers and assessed patient satisfaction. Study design: We conducted a prospective, descriptive, cross-sectional study. A survey of 100 women, of reproductive age attending the gynaecology out-patient department, was conducted using a questionnaire over a period of 3 months. Sample size was determined by use of The Survey System, Sample Size Calculator. The survey assessed the women’s knowledge regarding barrier methods as well as hormonal methods (in the form of combined oral contraceptives, injectables, the implant, the intrauterine device, emergency contraception) and permanent forms of contraception. Independent variables were age, level of education, employment, parity. Dependant variables were prevalence of contraceptive uptake, knowledge of available contraception. The association between the prevalence of contraceptive uptake and the knowledge regarding the available methods of contraception was assessed using the Chi square test, as well as the Mann Whitney U test. A p-value of 0.05 was decided upon for statistical significance an odds ratio and 95% confidence intervals were reported. Results: Overall Our study found that the total percentage of women using a method of contraception was 39.79 % while those that were not on any method of contraception was 60.20%. Our study also found that there were high rates of discontinuation of contraception. Overall,there was poor contraceptive awareness and knowledge. There was more awareness than there was intricate knowledge regarding the different forms of contraception. Contraceptive counselling increased the rate of contraceptive uptake; of the women that were initially counselled, and then offered contraception, 82.9% of them were agreeable. Conclusion: Awareness does not equal knowledge. All gynaecology out-patient visits should be seen as an opportunity for contraceptive counselling, regardless of the main complaint. The high rate of discontinuation of hormonal contraception should be further assessed, and women should be counselled prior to discontinuation, and preferably placed on another form of contraception which suits their needs
Presentation and outcomes of children admitted with organophosphate and carbamate poisoning at Rahima Moosa mother and child hospital
(University of the Witwatersrand, Johannesburg, 2023) Dlamini, Sibongile; De Maayer, Tim
BACKGROUND: Children are a vulnerable population for organophosphate and carbamate poisoning (OP/CBM). The World Health Organization reports mortality up to 10%. These agents then cause muscarinic, nicotinic and central nervous system collapse. OBJECTIVES: To describe the demographics and clinical features of OP/CBM poisoning, document the treatment given and the response thereof. Observe the acetylcholinesterase levels in relation to clinical features and assess outcomes of the participants. METHODS: A retrospective cross-sectional record review of patients (<14 years) presenting with OP/CBM poisoning at Rahima Moosa Mother and Child Hospital (RMMCH) from the 1st of February 2016 to the 31st of March 2018. Demographics, poisoning circumstances, clinical features, investigations, management and outcomes were analysed. RESULTS: Over the two-year period, 28 participants were included in the study. Gender distribution was equal, and the median age was 31,5 months (Interquartile range [IQR]: 17.5-32.0). Majority was due to accidental poisoning (85%). On arrival to RMMCH, 42.9% were unconscious, displaying mostly Nicotinic (85.7%) vs Muscarinic (71.4%) symptoms. All the participants received Atropine as part of their initial treatment. Participants that had poor outcomes (i.e., demised, n=6/28, 4.7%) were more likely to require inotropes (p=0.02), suffer seizures (p=0.003) and have metabolic acidosis (p=0.02). CONCLUSION: OP/CBM poisoning can have devastating outcomes. Improvement on trade, storage and legislation of these agents is of importance. Research on long-term effects of poisoning would be beneficial.
The effect of medical castration on lipid levels in black South African men with Prostate cancer
(University of the Witwatersrand, Johannesburg, 2024) Minkowitz, Shaul
Background In South Africa, androgen deprivation therapy (ADT) is commonly given as primary therapy for prostate cancer (PCa) due to many patients presenting with advanced disease. The metabolic adverse effects of ADT on lipid profile and weight gain have been reported mainly in Caucasian populations but few studies have been performed in African populations. Men of African descent generally have favorable lipid profiles compared to other populations and our study looked to analyze the effect of medical castration on lipid levels in black South African men with PCa. Methods The aim of this study is to describe the changes in blood total cholesterol, triglycerides, LDL and HDL at 6 months and at 1 year in men with prostate cancer newly initiated on ADT. Changes to BMI, waist circumference and HbA1c were also measured after 1 year of ADT. Our study was conducted at Chris Hani Baragwanath Academic Hospital which is a teaching hospital affiliated with the University of the Witwatersrand. It is located in Soweto, South of Johannesburg and serves the 1.3 million local residents who are predominantly black and of the lower income bracket. This study enrolled 38 black South African men who were starting to receive ADT for PCa. Subjects were evaluated at baseline and at 6 and 12 months. Lipid profiles and HbA1C levels were measured using blood samples and body composition was measure using BMI and waist circumference. Results In this prospective single center study we found that ADT resulted in a significant rise in triglyceride levels and weight gain in black South African men reaching mean levels of obesity using ethnic specific definitions. High density lipoproteins levels decreased significantly particularly in the first 6 months of treatment and thereafter began to rise. ADT also resulted in an increased HbA1C level which is a marker for insulin resistance. Conclusions Androgen deprivation therapy unfavorably changed the body habitus and lipid profile of men with PCa. It was demonstrated that even black South Africans who generally have favorable lipid profiles compared to their counterparts are at risk of developing metabolic syndrome while being treated with ADT
The feasibility of early chemical thromboprophylaxis in traumatic brain injury patients admitted to a trauma ICU
(University of the Witwatersrand, Johannesburg, 2024) Mathibela, Setoni
Trauma is a disease process that occurs because of man’s interaction with other people and the environment. Trauma is the leading cause of non-natural death, a significant cause of permanent disability, with the economically active population group most affected (1,2). Traumatic brain injury (TBI) characterises a major source of trauma-related mortality and is a leading cause of permanent disability in the young population (3). Traumatic brain injury commonly occurs in the background of polytrauma and remains a major obstacle in improving trauma outcomes. Mortality is directly attributable to TBI in up to one-third of patients who die after multiple injuries (4)
An assessment of the hospital learning environment within the Univesity of Witwatersrand obstetrics and gynaecolgy registrar training programme
(University of the Witwatersrand, Johannesburg, 2023) Masukume, Rumbidzai; Chauke, Lawrence; Odell, Natalie
Background. The hospital educational environment is a critical component of a health professionals’ education. It influences clinicians’ professional development, well-being, academic success and ability to provide high-quality healthcare services. There is limited data on the postgraduate clinical learning environment (CLE) in obstetrics and gynaecology (Obgyn) in South Africa. Research objectives. (1) to evaluate obstetrics and gynaecology registrars’ perceptions of their CLE utilising the modified Postgraduate Hospital Educational Environment Measure (PHEEM) questionnaire, (2) to assess factors influencing these perceptions; (3) to evaluate the impact of the learning environment on academic outcomes, and (4) to use the results to recommend targeted improvements of the registrar training programme in Obgyn at the University of Witwatersrand (WITS). Methods. A prospective cross-sectional study involving a convenience sample of doctors enrolled for the four-year Obgyn training programme at WITS. The modified PHEEM questionnaire was electronically sent to 80 participants between January and April 2022. Categorical variables were described using frequencies and percentages. Continuous variables were summarised by measures of central tendency. Factors associated with the PHEEM scores were evaluated using the Student’s t-test and analysis of variance (ANOVA) tests. A p-value of <0.05 was considered statistically significant. Results. Of the 80 participants, 46 (57.5%) responded to the questionnaire. The mean total modified PHEEM score (SD) was 74.9 (16.4) out of a possible 160. The mean scores in this study were as follows: perception of autonomy 27.4/56 (5.3), perception of teaching 30.2/60 (4.0), and perception of social support 17.3/44 (7.1). The overall perceptions of the educational environment were influenced by sex (p<0.001), supernumerary status (p= 0.0036), and marital status (p=0.001). Only two individuals did not complete the four-year training programme. A total of 81.8% of those who completed the four-year training programme passed their Fellowship of the College of Obstetricians and Gynaecologists (FCOG) of South Africa qualifying exams (FCOG 2) on their first exam attempt, however, 34.1% wrote the FCOG 2 exams after completing the four-year training. Conclusion. During the study period, the educational environment within the Obgyn WITS circuit was perceived to be more negative than positive, indicating that all three domains of the modified PHEEM require attention to enhance the educational environment.

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