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    Euthanasia and Physician-assisted Suicide in South Africa: Towards an Ethico-legal Framework to assist Medical Practitioners with End-of-life Decision-making
    (University of the Witwatersrand, Johannesburg, 2023-07) Guidozzi, Yolande; Dhai, Ames; Egan, Anthony
    South Africa is confronted with court challenges from people who fear intractable suffering from terminal illness requesting assisted death. Euthanasia (E) and physician assisted suicide (PAS) are still criminal offences in South Africa. Where they have been legalised internationally, the concept has been ‘medicalised’ because of the role medical practitioners are asked to fulfil to enable it. The aim of the study was to investigate South Africa’s ethical and legal environment on end-of life choices. In particular E and PAS in foreign countries was examined to propose a sound ethico-legal framework to assist South African doctors and the legislature to deal with end-of-life decision-making going forward. Well-known philosophical theories and their use in solving bioethical dilemmas, South African case law, and established E/PAS legislation, were canvassed to produce draft South African legislation and recommendations for the management of end-of-life decision-making. The controversial role of medical practitioners in the delivery of E/PAS was analysed. Significantly, the World Medical Association does not presently support E/PAS. It was found that foreign end-of-life models, which generally utilise medical practitioners and health services to facilitate E/PAS, would not be suitable for South Africa. If South Africa were to opt for legalisation of assisted dying, it is proposed that the process be kept outside of the health care service to ensure that it is never perceived to be an extension of medical care. To achieve this, an alternative end-of-life care model is suggested where nongovernmental organisations manage the procedure. Ultimately it was concluded that without a strong palliative care system and income equality, legislation of E and PAS is not yet an option for South Africa. Focus and resources should be directed rather at improving universal access to good palliative and health care. An ethico-legal framework to assist South African doctors with end-of-life decision-making is proposed.
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    Strengthening understanding of effective adherence strategies for first-line and second-line antiretroviral therapy (ART) in selected rural and urban communities in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Gumede, Siphamandla Bonga Ziphozonke
    South Africa accounts for approximately 20% (4.8 million) of the worldwide population of individuals who are HIV-positive and receiving antiretroviral medication (ART). In 2019, approximately 15%-20% of individuals receiving first-line antiretroviral therapy (ART) and up to 30% of individuals receiving second-line ART in the HIV treatment program in South Africa encountered virological failure. In addition, over 40% of individuals receiving first-line antiretroviral therapy (ART) and up to 20% of individuals receiving second-line ART experienced loss to follow-up (LTFU). While there is a significant amount of research on adherence to antiretroviral therapy (ART), there is still a lack of studies examining the various elements at different levels that influence adherence to treatment and the processes that shape adherence behaviour, specifically in South Africa. Furthermore, there exists a dearth of documented information regarding the efficacy and consequences of the measures presently utilized to enhance adherence among individuals living with HIV (PLHIV) who are undergoing antiretroviral therapy (ART). This thesis employed a multilevel socio-ecological framework to elucidate the risk factors that influence treatment adherence across various levels. Additionally, it conducted a comprehensive evaluation of existing research that examined the impact or impacts of intervention techniques on enhancing treatment adherence. The studies presented in this thesis identified the barriers to and facilitators of adherence for people living with HIV on ART and assessed the impact of different adherence intervention strategies that aimed to promote treatment adherence. This was achieved by examining the five research questions: 1. What is the uptake rate of ART, and the individual-level predictors of virological failure and being lost to follow-up (LTFU) in PLHIV taking ART in urban communities? 2. What are the individual-level factors that predict virological failure, low CD4 count, and retention in care for patients on second-line ART in urban communities? 3. What are the individual, relationship or interpersonal, and community-level factors associated with self-reported adherence, pill count, and virological failure to ART in rural communities? 4. What are the different treatment-taking behaviours and perspectives on adherence to ART between virally suppressed and unsuppressed patients on second-line ART in urban communities? 5. What treatment adherence strategies and interventions have been implemented and evaluated in sub-Saharan Africa for ART, hypertension, and Diabetes Mellitus? vii Chapter 2, a protocol paper, detailed the rationale, study aims, research designs, and methods employed in the studies reported on in this thesis. By adapting a multi-level socio-ecological framework to identify factors existing at various levels (including individual, relationship/interpersonal, and community level factors) and describing their interplay chapter 2 demonstrated how an existing socio-ecological conceptual framework can be used as a tool to provide guidance regarding facilitators and barriers to ART adherence. In the study reported in chapter 3, we described the ART uptake and the individual level predictors of virological failure and being LTFU in PLHIV taking ART in Johannesburg. In this retrospective cohort study, we presented analyses based on the TIER.Net database for a large cohort of HIV- infected adult patients who are taking first-line and second-line ART in Johannesburg, South Africa. TIER.Net is the ART monitoring and evaluation system used by the South African National Department of Health for recording ART patient-level information. Records were reviewed for patients on ART from seven high-volume public health facilities in Johannesburg. Study data included medical records of people with HIV who started ART between 01 April 2004 (the inception of the South African national HIV treatment program in the public health system setting) and 29 February 2020. This cut-off period was chosen to give the cohort patients a minimum of one year to receive their annual standard-of-care viral load test. In this study, factors such as age at ART start, current age, sex, duration on ART, baseline CD4 cell count, and retention in care were analyzed as covariates of outcomes (viral load and LTFU). Of the total study cohort, 95% (n=117 260/123 002) were on a first-line regimen and 5% (n=5 742/123 002) were on a second-line regimen. Most patients (59%, n=72 430/123 002) were initiated on an efavirenz-based, tenofovir disoproxil fumarate-based and emtricitabine-based regimen (fixed-dose combination). 91% (n=76 737/84 252) achieved viral suppression at least once since initiating ART and 59% (n=57 981/98 071) remained in care as at the end of February 2020. Findings from the univariate, multivariable logistic regression analysis and fixed effect model showed that younger patients, male patients, patients with low CD4 cell counts, and patients who were initiated on ART between 2004 and 2010 all had poorer clinical, treatment and retention outcomes, particularly those on second-line ART. While national ART guidelines and efforts to initiate PLHIV on treatment have contributed to a higher uptake of ART over time, much still needs to be done to improve retention in care. Although slight efforts have been made to address similar findings in sub-Saharan Africa, these demographic and clinical characteristics must be considered when designing/implementing treatment support strategies and models to improve treatment outcomes, retention in care, and subsequently treatment failures which lead to switching to more complex ART regimens. viii In the study reported in chapter 4, we aimed to identify individual-level factors that predict virological failure, low CD4 count, and retention in care for patients on second-line ART in Johannesburg. In this retrospective cohort study, we conducted analyses of secondary data that was exported from the TIER.Net database. Variables extracted included ART start dates, ART switch dates, treatment retention, viral load, and CD4 cell count results. This retrospective study of 825 PLHIV on second-line ART reported viral load suppression of 83% (n=570/686) among patients on second-line ART, demonstrating lower suppression rates compared to historic first- line treatment (92% suppression rate) in Johannesburg. Just under three-quarters (72%, n=597/825) of the patients remained in care over the reported period, slightly lower than the reported retention rate of 78% in a first-line treatment cohort from Johannesburg. Results from the multivariable logistic regression analysis reported that being <25 years of age, male sex, and geographical transfer (started initial treatment in a different region) independently predicted low CD4+ cell counts and virological failure on second-line treatment. Being younger than 25 years of age, male sex, and transferred-in patients, are easily identifiable factors that may trigger the need for added adherence and support interventions, which include targeted adherence and retention support programs, using mobile health solutions for patient communication, education, and appointment reminders. The study presented in chapter 5 investigated individual, relationship or interpersonal, and community-level factors associated with self-reported adherence, pill count, and virological failure to ART of patients accessing care at the Ndlovu Medical Centre, Limpopo Province. This study was performed as a sub-study of the Intensified Treatment Monitoring Strategy to Prevent Accumulation of Drug Resistance (ITREMA) randomized clinical trial, a well-characterized cohort of 501 participants on antiretroviral treatment, that received prospective long-term follow-up for 96 weeks. In this study, markers of adherence and virological suppression status were periodically assessed. A comprehensive assessment of multilevel risk factors at the baseline of this trial enabled us to characterize their association with study outcomes (viral load, self-reported adherence, and pill count). The multilevel factors included demographic information, employment status, income composition, household composition, partnership status, food security, adherence, actual support from household members, actual family support, coping abilities, clinician trust, health literacy, mental health, and stigmatization. We found that over half (53%, n=243/458)) of the participants reported difficulties with adherence, and over one-third (35%, n=162/458) had suboptimal adherence measured through pill count (pill count<95%) at any point during follow-up. Virological failure appeared infrequently and occurred in 16% (n=68/436) of participants. Using tests of association and multivariable logistic regression analysis (stratified by sex), we found that being male was an independent risk factor for self-reported difficulties with adherence, suboptimal adherence measured through pill ix count, and virological failure. PLHIV who experienced moderate or severe depressive symptoms or had low household income were at increased risk of poor adherence and/or virological failure and may benefit from additional ART adherence support. In the stratified analysis, we found that the risk of virological failure was higher among male participants with food insecurity. We also found that while the prevalence of depressive symptoms was similar between males and females, the association was significant among female participants only. Task-oriented coping was associated with suboptimal adherence as indicated by pill count<95%. Our findings reported in chapter 5 contribute to the available knowledge on risk factors for adverse outcomes of ART in rural populations. The study findings may also contribute to the ongoing development of ‘rural proof’ healthcare policies currently being introduced in South Africa, such as the National Health Insurance and the new 2030 Human Resources for Health Strategy. These strategies seek to promote comprehensive access to healthcare services and also highlight the need for the government to take decisive steps to improve access to care for all individuals seeking healthcare services. Chapter 6 reports a cross-sectional study that sought to describe the different treatment-taking behaviours and perspectives of adherence to ART between virally suppressed and unsuppressed patients using second-line ART in Johannesburg. This study was conducted between July 2018 and August 2018, in five public health facilities (two hospitals, one community health center, and two primary healthcare clinics). We randomly sampled 10% of the population of 1 500 eligible patients and they were invited to participate in this study in one of two ways; telephonically or in facility recruitment where researchers met them at the facility during their scheduled clinic visit. The study sample comprised 149 participants; of which 48% (n=71/149) were virally unsuppressed. The majority of participants (63%, n=94/149) had disclosed their HIV status to their relatives and/or partners within one week of diagnosis. However, 28% (n=42/149) took longer than four weeks to disclose to their relatives and/or partners. Using multivariable logistic regression analysis, we found that single and unmarried people living with their partners were more likely to experience virological failure compared to those who were married. The more toxic second-line multi-pill, which is taken multiple times a day, was seen as significantly harder to take than a single tablet daily, well-tolerated first-line regimen. Participants experiencing medication- related difficulties in taking second-line ART and experiencing side effects were also subjective predictors of virological failure. We also found that participants with virological failure were more likely to have treatment-related side effects. Those participants with side effects were more likely to be unemployed. In general, employed individuals are linked to improved access to healthcare and better health outcomes as compared to their unemployed counterparts. However, while the correlation between improved health outcomes and employment exists, the causal relationship is x complicated as the relationship can be bi-directional. Our study results suggest the importance of improving patients’ knowledge about treatment and adherence, and motivation to continue ART use despite the persistence of side effects. Participants interviewed in the study reported in chapter 6 had firm recommendations around improving adherence to second-line ART, largely focused on reduced dosing and pill burden. These included a second-line fixed-dose combination, a dosage taken once a day, and a reduction in the pill size. Furthermore, the participants suggested that education on the benefits of taking ART could improve adherence, whilst a few participants also suggested the implementation of injectable second-line ART. In chapter 7, we report a systematic review that assessed the impact of interventions that aimed to promote adherence to treatment for chronic conditions (ART, hypertension, diabetes mellitus). We systematically searched the PubMed, Web of Science, Scopus, Google Scholar, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases to identify relevant publications. Data were extracted from eligible studies for study characteristics and description of interventions for the study populations of interest. We found a relatively large body of evidence on interventions to improve adherence among adults living with chronic conditions in sub-Saharan Africa. Of the 25 473 total studies/records screened, a total of 77 studies were subsequently included, describing a total of 49,364 patients. Of the total included studies, 70% (n=54/77) were related to ART for HIV, 8% (n=6) were anti-hypertensive medication related, 16% (n=12/77) were anti- diabetic medication related and 6% (n=5/77) focused on medication for more than one condition. Of the total 77 studies, 60% (n=46/77) reported improved adherence based on the described study outcomes while 21% (n=16/77) reported no significant difference between studied groups. There is expanded evidence that community-and home-based, digital or mobile health (mhealth) and adherence counselling interventions can improve adherence to treatment for chronic conditions. Our findings underscore the need to develop a gold standard (or uniform measures) for measuring adherence. In the general discussion in chapter 8, the main findings were summarized, collated, and discussed. Chapter 8 provided context to the findings about the research questions and discussed its implications for future research along with recommendations. Thereafter, the strengths, limitations of this thesis, and directions for future research were also discussed. Combining multi-level models, the evidence from the studies presented in this thesis enabled us to identify the barriers to and facilitators of adherence for PLHIV on first-line and second-line ART and make recommendations for comprehensive, acceptable, and appropriate intervention strategies to improve treatment adherence. Our research found that many factors influence the xi ability to successfully engage individuals in HIV care. These factors include being male, being younger, experiencing ART-related side effects, having a low household income, presence of food insecurity, and experiencing moderate or severe depressive symptoms. With a large total sample size of 173 842 people included across all studies, our research ensured that a strong body of evidence was created regarding barriers to and facilitators of adherence to ART and adherence intervention strategies implemented to improve treatment adherence. However, all the research studies included in this thesis were conducted in a total of eight health facilities (seven of over 120 health facilities in one South African metropolitan municipality (urban setting) and one facility in a rural setting). While this ensured that study participants had comparable demographic profiles throughout the different studies in this thesis, these findings may not be generalizable to other regions or municipalities in South Africa, or other country settings. However, the research included in this thesis have sufficient sample sizes to enhance the impact of the findings. Furthermore, the magnitude and direction of the impact remained consistent throughout all chapters, indicating that the study results may be strong despite constraints associated with the study's conditions. Utilizing our study findings to enhance adherence intervention tactics is expected to enhance health outcomes and reduce the rate of patients transitioning to more intricate treatment alternatives, such as second-line and third-line ART regimens.
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    Temporal changes in Streptococcus pneumoniae colonization in children following routine childhood immunization with pneumococcal conjugate vaccine in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Downs, Sarah Leah Robina; Madhi, Shabir
    Background: Streptococcus pneumoniae remains a leading cause of morbidity and mortality in children <5 years old in sub-Saharan Africa. Pneumococcal conjugate vaccines (PCVs) reduce pneumococcal-associated disease by reducing vaccine-serotype (VT) circulation. Monitoring serotype-specific nasopharyngeal colonization can serve as a proxy to evaluate the impact of vaccination against VT disease. Sensitive tools for detecting pneumococcal serotypes and other bacterial species are required. Current real‑time Polymerase Chain Reaction (PCR) methods do not fully distinguish 13-valent PCV (PCV13) serotypes from non-vaccine serotypes (NVT). The 7-valent-PCV (PCV7) was introduced in the South African immunization program in 2009 (replaced by PCV13 since 2011) using a 2+1 schedule (at 6, 14, and 40 weeks of age). In this study, the impact of routine PCV immunisation on pneumococcus, and other bacterial colonisation among rural (Agincourt, Mpumalanga) and urban (Soweto, Gauteng) dwelling South African children <5 years old, was evaluated 8-9 years after PCV introduction using a comprehensive, real-time PCR. Methods: Designed and previously published assay-sets were combined into a 96-assay reaction set within a nanofluidic real-time PCR platform. The reaction‑set was optimized using reference isolates and synthetic calibrators for analytical performance. To validate the reaction set, diagnostic performance was evaluated through blind analysis of 1 973 archived nasopharyngeal swab samples (NPS) previously serotyped with the referent standard culture‑based Quellung method. The reaction set was applied to NPS collected from children across two study periods, during the early PCV introduction period and after 8-9 years of routine immunization. In Period-1, 630 NPS collected in May to October 2009 were available from Agincourt and 1135 NPS collected in May 2010 to February 2011 were available from Soweto. In Period-2, NPS were collected from 568 children in July 2017 to February 2018 in Agincourt, and 571 children in June to December 2018 in prospective colonization surveys. 1vii Results: The real-time PCR reaction set was analytically sensitive (limit of detection <102 gene equivalents), efficient (90–110%), and had low variation between replicates (r2 > 0.98) for relative quantification. The diagnostic sensitivity and specificity of the reaction set was >80% and >95% respectively for all assay-sets that targeted serotypes previously detected by Quellung at a prevalence >1%. Comparing Period-2 to Period-1, in Agincourt and Soweto, there was a lower overall (76.9% vs. 83.2%; adjusted Odds Ratio [aOR]: 0.65, 95% confidence interval [CI]: 0.48-0.87 and 49.4% vs. 68.1%; aOR: 0.66; 95% CI: 0.54-0.88, respectively) and PCV13-VT colonisation prevalence (14.3% vs. 51.0%; aOR: 0.16, 95%CI: 0.12-0.21 and 18.6% vs. 40.9%; aOR: 0.41; 95% CI: 0.3- 0.56). In Period-2, residual colonization by 19F (5.3% and 8.1%) remained high in both settings compared with Period-1 (10.3%, aOR: 0.52, 95%CI: 0.33-0.82 and 6.6%; 75/1135; aOR: 2.0; 95% CI: 1.09-3.56, respectively). Non-vaccine-serotype (NVT) colonisation was higher in Period-2 in Agincourt (63.2%) than Period-1 (35.6%, aOR: 3.12, 95%CI: 2.45-3.97), while there was no difference in NVT in Soweto between the two periods (37.8% vs. 42.4%; aOR: 0.96, 95% CI: 0.72-1.26. In Agincourt, there was a higher prevalence in Period-2 compared with Period-1 of Acinetobacter baumannii (36.8% vs 1.1%, aOR: 50.11, 95%CI: 23.14-108.50) and Klebsiella pneumoniae (13.2% vs 0.6%, aOR: 22.16, 95%CI: 8.03-61.11). Conclusions: The high‑throughput nanofluidic real‑time PCR method simultaneously detects 15 bacterial species and 92 pneumococcal serotypes, distinguishing to 57 single serotypes and 35 serotypes within 16 subgroups, using 73 serotyping, and 23 bacterial detection assay-sets in 96 samples (including controls), within a single qPCR run. There was an 80% and 59% reduction in colonization by PCV13-VT serotypes in Agincourt and Soweto, 8-9 years after introduction of routine immunisation with PCV, however, there was high residual prevalence PCV13-VT (14.3-18.6%) despite >90% of enrolled children >40 weeks being immunized with PCV in both settings, mainly due to serotype 19F.
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    Ocular Surface Squamous Neoplasia: Risk factors, diagnosis, management and outcomes at a Tertiary Eye Hospital in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Höllhumer, Roland
    Introduction: Ocular surface squamous neoplasia (OSSN) is the most common ocular surface tumour with a high burden of disease in sub-Saharan Africa. In high-income countries it typically affects older males and in low-income countries younger females. The commonly described risk factors for OSSN include ultraviolet-B radiation exposure, HIV and human papillomavirus (HPV) infection. Diagnosis is suspected clinically and confirmed with histology or other less invasive tests. Management of OSSN can be divided into two main groups, surgical and medical. Surgical management has been the primary management approach traditionally. It is indicated when four or less limbal clock hours are involved and when the basal tumour diameter is less than 15mm. This ensures that the main complication from surgery, limbal stem cell failure, is avoided. Medical therapy is used for larger tumours and includes interferon α2b, mitomycin-C and 5- fluorouracil (5FU). Methods: We conducted an interventional prospective study. Patients that presented between December 2019 and February 2022 with conjunctival masses suspicious of OSSN, or symptomatic conjunctival growths despite medical therapy were considered for inclusion in the study. An electronic questionnaire was completed at enrolment to document demographic data, presenting history, and associated risk factors. A clinical examination and anterior segment photography were performed with slit lamp to document clinical features. Optical coherence tomography (OCT) and methylene blue stain were performed at the initial visit, with liquid-based cytology (LBC) and biopsy for histology at the time of surgery. Masses suspicious of OSSN that occupied less than or equal to four clock hours of the limbus had an excision biopsy with 4mm margins using ix the Shields no-touch technique and double freeze-thaw cryotherapy to the limbus and free conjunctival edge. Larger lesions had an incision biopsy performed to confirm diagnosis and received topical chemotherapy in the form of 5FU. Positive surgical margins and recurrence were managed with 5FU. The participants were followed up for 24 months. Results: One hundred and seventy-five patients were enrolled in the study. Based on biopsy results, 130 were defined as OSSN cases and 45 as benign controls. Median age was 44 years (IQR: [35-51]) with an equal gender distribution in cases. The prevalence of HIV in cases was 74% and was strongly associated with OSSN (p<0.001). Conjunctival intra-epithelial neoplasia made up 82% of cases. There were 182 conjunctival masses among the 175 patients for which three non- invasive diagnostic tests were evaluated (OCT, cytology and methylene blue). There were 135 lesions identified as OSSN on biopsy and 47 lesions were benign. OCT had a sensitivity and specificity of 87.2% (95% CI: 80.0 – 92.5) and 75.6% (95% CI: 60.5 – 87.1) respectively, when an epithelial thickness cut-off of 140μm was used. LBC had a sensitivity of 72.4% (95% CI: 62.5 – 81.0) and specificity of 74.3% (95% CI: 56.7 – 87.5). Methylene blue had a high sensitivity of 91.9% (95% CI: 85.9 – 95.9), but low specificity of 55.3% (95% CI: 40.1 – 69.8). One hundred and nine patients with 114 conjunctival masses completed at least three months of follow-up and were assessed for outcomes. Ninety-four percent (n=107) of patients had surgery as their primary management, with a recurrence rate of 0.9%. Seven patients had 5FU as primary therapy with a resolution rate of 71% and a recurrence rate x of 14%. All patients with partial resolution to 5FU resolved with surgery and additional cycles of 5FU. Side effects from 5FU were mild and did not result in cessation of therapy. Discussion: Our study describes a middle-aged demographic with no gender predisposition and has HIV as the primary assessed risk factor. The age of presentation is slightly younger than other middle-income countries, presumably due to the high prevalence of HIV in South Africa. The histology profile of the tumours was mostly premalignant, which is different from other African countries that show a predominance of SCC. Our study also showed a high percentage of pigmented tumours (55%). Three minimally invasive diagnostic tests were evaluated. OCT performed the best and is a reliable alternative to histology. LBC performed well, but was found to be inferior to OCT. Our main rationale for investigating the use of LBC was to have a biologic specimen with which to conduct ancillary tests, such as HPV polymerase reaction. Methylene blue performed well as a screening test and could be used at a primary care level to assess urgency of referral. We used a standardised management approach which had high resolution, low recurrence rates and had low morbidity for the patient. Conclusion: Our study provides essential data on the urban South African patient with OSSN. We have a middle-aged demographic with no gender predisposition, most of our patients have HIV as a risk factor, and present with premalignant disease. OCT performed well as a non-invasive diagnostic test, with LBC a promising new modality. A combined surgical and medical management strategy yielded high resolution and low recurrence rates.
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    A study of the physiology of pepsinogen in the human with special reference to its disturbance in diseases of the upper gastro-intestinal tract
    (University of the Witwatersrand, Johannesburg, 1953) Hirschowitz, Basil Isaac; Jones, F. Avery
    This study was originally undertaken to determine the clinical value of estimating pepsinogen in the urine in cases of peptic ulcer because recent publications had shown that uropepsin (urinary pepsinogen) excretion in ulcers differed from normal controls. Briefly, the state of knowledge of pepsinogen when this study was undertaken was as follows: pepsinogen was discovered by Langley in 1881 and eventually isolated in 1958 by Herriot who described its physico-chemical properties. It was known to be formed in the stomach wall and mainly secreted into the stomach where it was irreversibly changed into pepsin in the presence or hydrochloric acid. None was reabsorbed and this pepsin was destroyed in the alkaline small intestine. Some pepsinogen diffused directly into the blood stream from the peptic cells and as far as could be ascertained was lost, till it appeared in the urine - a fact discovered by Brucke in 1861. Its transport to and the mechanism of its excretion by the kidney were the subject of hypothetical discussion only. In disease urinary pepsinogen had been studied for some time and the final conclusions were that it was increased in ulcers, especially duodenal ulcers and decreased or absent in pernicious anaemia. It was apparent early in this study that investigation of urinary pepsinogen alone would be of little value in advancing the knowledge of the normal and abnormal physiology of pepsinogen in the human. The investigation was then extended to study the pathological disturbances of urinary pepsinogen more closely, and if possible to determine what happened to pepsinogen between the stomach and the urine. This latter project became possible after the development of a technique not previously described for determining blood pepsinogen and it was found that pepsinogen diffuses from the peptic cells into the blood, and circulate as free pepsinogen in the plasma. From the plasma it is freely diffused through the body and filtered through the glomerular membrane and then reabsorbed in the tubules of the kidney to the extent of 65 - 95%. This new concept of pepsinogen excretion by the kidney calls for a re-orientation of the conclusions previously held of the significance of the urinary pepsinogen in disease, In this report, an attempt is made to present the whole cycle of pepsinogen metabolsim from its formation in the stomach to its appearance in the urine, with-normal and abnormal variations, as a unified concept. While in places comments or conclusions may appear dogmatic, it is realized that this study has produced more questions than answers. It is hoped, however, that a small contribution will have been effected by this work towards a better understanding of the direction of further advances in the knowledge of the aetiology and pathological behaviour of peptic ulcers.
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    The Use of Social Media Platforms in Implementing Quality Improvement Initiatives for Quality Assurance of Paediatric Chest Radiographs in Radiological Departments of Varying Radiographer Expertise
    (University of the Witwatersrand, Johannesburg, 2024) Hlabangana, Linda Tebogo; Andronikou , Savvas
    Introduction Chest radiographs are the most widely performed diagnostic imaging test in children. Good quality radiographs assist in making the correct diagnosis. In resource limited settings, such as in Africa, there are several limiting factors that affect the quality of the radiograph which go beyond the availability of equipment and human resources, including geopolitical and socioeconomic challenges. Novel innovations are required to overcome these challenges by leveraging off technology and the widespread distribution of smart phones. Aim The aim of the study was to evaluate the improvement in the quality of chest radiographs performed in children after initiating quality improvement interventions at three radiology departments. The interventions used the Internet, Facebook® and Twitter®) to remotely communicate with the radiographers. Methods A longitudinal, descriptive study was performed at three radiological centres in South Africa. They study had a retrospective phase (before intervention), and a prospective phase. Over a period of six months, communication on quality factors of chest radiographs and how to improve quality were sent out using Facebook and Twitter. Thereafter, radiographs were collected and the quality assessed. Results A total of 966 radiographs were included in the study. The most common errors overall were “scapula in the way” (38.7%), “rotation” (34.7%) and “poor collimation” (22.2%). The errors “parts cut off” (1.3%) and “wrong/no left/right marker” (1.7%) were the least common. Rahima Moosa Mother and Child Hospital demonstrated non-significant improvement in the quality of radiographs over the duration of the study. The other two centres demonstrated no significant or sustained improvement in the quality of chest radiographs performed. The research did not demonstrate a significant benefit from the intervention. There was vi low engagement with the social media platforms. A total of six radiographers followed the Twitter handle and the Facebook page had 37 friends/followers, eight of these were radiographers participating in the study. Conclusions Although social media have demonstrated impactful use in education and communication, the usage by radiographers in South Africa to improve the quality of chest radiographs is limited. . There was no significant benefit demonstrated from the use of Facebook and Twitter as educational and information tools. Further research using low-data consumption social media apps to create locally relevant and sustainable solutions for quality assurance and quality improvement in radiography are required.
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    The Feasibility of Introducing a Harmonised Treatment Regimen, Comparing Affordable Blood Tests and PET-CT Scans, to Improve Two-Year Survival Rates in Children, Adolescents and Young Adults with Hodgkin Lymphoma in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Geel, Jennifer Ann; Ballot , Daynia; Metzger, Monika
    Paediatric classical Hodgkin lymphoma (cHL) is highly curable using chemotherapy and radiotherapy. Prior to this study, no collaborative, prospective cHL studies had been performed in South Africa. The retrospective assessment informed the creation of the prospective harmonised guideline. We aimed to determine a baseline survival rate and prognostic factors; explore reasons for mortality in HIV-positive patients, assess the feasibility of introducing a harmonised treatment guideline, prospectively assess survival and analyse the prediction of chemosensitivity at interim assessment. In the retrospective analysis, multiple potential prognostic factors were analysed and survival rates calculated with Kaplan-Meier curves and Cox regression analysis. An initial survey was conducted of the clinical researchers before the launch of the prospective study, followed by a mid-study assessment. Two-year overall survival was calculated by Kaplan-Meier curves and computer-learning models were utilised to compare chemosensitivity based on interim PET-CT assessment with changes in haematological and non-specific markers of disease activity. The retrospective analysis accrued 294 patients, of whom 29 were HIV-positive. The 5-year overall survival was 84% in HIV-negative and 49% in HIV-positive patients. Advanced stage, HIV infection and treatment with regimens other than doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) were associated with lower survival rates. In HIV-positive patients, an AIDS-defining CD4 count and hypoalbuminaemia were associated with poorer prognosis. The pre-study assessment indicated that the majority of centres fulfilled all criteria to participate in the study. The mid-study assessment identified barriers to participation and methods to mitigate these challenges. Analysis of 132 prospectively accrued patients (19 HIV-positive, 113 HIV-negative) treated on a risk-stratified, response-adjusted treatment regimen resulted in higher survival rates of 93% in HIV-negative and 89% in HIV-positive patients. Changes in low-cost, widely available blood tests correctly predicted chemosensitivity, identifying patients who may not require radiotherapy. In conclusion, higher survival rates for paediatric cHL were documented following the introduction of a harmonised management guideline in South Africa. In settings that do not have access to PET-CT, changes in affordable blood tests may be used to substitute for xvi radiological interim assessment, although a format suitable for individual patients is yet to be developed for the clinical setting. This research marks the inaugural collaborative effort where patients from every South African paediatric oncology unit and the majority of private paediatric oncology practices, were afforded the opportunity to participate in a prospective study aimed at enhancing survival rates.
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    The use of ultrasound compared to an age- based formula to estimate endotracheal tube size in an academic hospital
    (University of the Witwatersrand, Johannesburg, 2024) Heslop, Donovan; Leonard, Tristan; Redelinghuys, Cara
    Background An accurate estimation of tracheal diameter for endotracheal tube size selection is imperative in the pediatric population, with ultrasound shown to be an acceptable and superior method of endotracheal tube size estimation when compared to conventional age-based methods. Aim To compare the accuracy of endotracheal tube size estimation using airway ultrasound to age-based formula in the South African pediatric population. Methods This was a prospective observational study, with 54 patients, American Society of Anesthesiologists physical status I–III, aged two to 12 years old, scheduled for elective surgery at Chis Hani Baragwanath Academic Hospital, South Africa. Patients were allocated to two groups, the age-based method group or ultrasound method group. The accuracy of each method used for endotracheal tube estimation was assessed using a standardized leak test. Post intubation endotracheal tube cuff pressures were measured and post operative follow up was done to assess for features of airway injury. Results The ultrasound method was a more accurate estimate of endotracheal tube size (74.47%) compared to the age-based method (29.63%) (p = 0.0011). In all cases a cuffed endotracheal tube was used. No difference was seen between the mean endotracheal tube cuff pressure between the groups with a large proportion of patients having underinflated endotracheal tube cuffs. Conclusion Ultrasound is a more accurate predictor of appropriate ETT size in the pediatric population compared to a conventional age-based formula. The use of ultrasound for the estimation of ETT size is an accurate, non-invasive, and reproducible technique with potential for long-term cost saving and reduced complications. Ultrasound is iii becoming readily accessible in the theatre setting in South Africa and with appropriate training and expertize, this bedside tool has the potential for more widespread uptake and may be a more accurate means of determining endotracheal tube size in children.
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    Developing an Intervention to Improve Informed Decision-Making for Oncology Patients in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Blanchard, Charmaine Louise; Norris, Shane
    Introduction Patients making cancer treatment decisions face several challenges including grappling with difficult terminology and deliberating different options based on the information provided and their own values while experiencing high levels of stress. Informed cancer decision making by South African patients in the public healthcare sector, is further complicated by the constrained resources in the oncology clinics limiting the time available for consultations with the oncologists. Language and socio-cultural barriers impact on the patient’s ability to make fully informed treatment decisions, which are legally and ethically required. While decision aids (DAs) exist in high income countries (HICs) to assist patients to make informed cancer treatment decisions, there are no studies reporting the development of cancer treatment DAs in South Africa. Aim The aim of this thesis was to develop a decision support intervention (DESI) to improve cancer patient informed treatment decision making. Methods This thesis applied the Intervention Mapping (IM) framework to the development of the DESI. The three objectives of the thesis related to the first step of the IM process namely a needs assessment to develop the logic model of the problem. The first objective was to assess the effectiveness of decision aids (DAs) in addressing vulnerable patient-reported decision needs by conducting a mixed methods systematic review to understand the synergies and gaps between the DAs and the patients’ needs. For the second objective a quantitative study was undertaken to measure the South African patient’s health literacy (HL), factors associated with HL, their decision control preferences (DCPs), and to assess their decision needs. The study enrolled 124 patients diagnosed with cancer at three tertiary level oncology clinics in South Africa (two in Gauteng and one in KwaZulu Natal). For the third objective a qualitative study was undertaken to understand the patient experiences of making cancer treatment decisions and the oncology staff perceptions of the decision- making process. In-depth interviews with 30 patients and eight focus groups with oncology staff were conducted at the same clinical sites as the quantitative study. The results of the XVII three studies were triangulated to provide a logic model of the problem which informed the next steps of the IM process, resulting in an evidence-based theory driven intervention program. Results The systematic review identified significant gaps between the DAs and the vulnerable patients’ decision support needs, particularly relating to communication in the consultation and providing counselling and coaching support for decision-making. The 124 South African patients at the study sites in Gauteng and KwaZulu Natal had mostly marginal (69%) to limited (11%) health literacy, positively associated with their level of education (OR 2.2, 95% CI 0.58 – 8.55 for high school and OR 14.6 95% CI 2.2 – 96.61 for tertiary education) and socio-economic status (OR 4.1, 95% CI 1.03 - 15.98, for the wealthiest tertile). The patients reported high information needs (71%) despite reporting understanding a lot of what the doctors explained (77%) and feeling comfortable a lot, asking questions (82%) in the consultation. Most patients (82%) preferred an active decision-making role. The qualitative study findings confirmed the high levels of information needs, but most patients did not ask questions in the consultation and often played a passive role in decision-making. Language and cultural differences between the patients and the oncologists were identified by oncology staff as major barriers to informed decision-making, and support from the patients’ families, the oncology nurses and the palliative care teams addressed some of the patients’ decision needs. Following the logical, iterative process of the IM framework a locally relevant decision support intervention program was developed. Conclusion Patients have high levels of cancer and treatment information needs and wish to be active participants in their treatment decision making yet often lack the self-efficacy to engage in treatment deliberation with their oncologists. Language and cultural discordance between the patient and oncologist compounded by the time pressures of the clinic, are barriers to effective patient-centred communication in the consultation. It is vital that adequate training is provided to oncologists to improve culturally sensitive patient-centred communication when supporting cancer patients to make informed treatment decisions.