Doctoral Degrees (Paediatrics and Child Health)

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    Nutritional status of children at cancer diagnosis and during treatment, with a focus on the association with their clinical outcome
    (Stellenbosch : Stellenbosch University, 2023-09) Schoeman, Judith; Kruger, Mariana; Ladas, Elena; Rogers, Paul; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
    ENGLISH ABSTRACT: Up to 50% of children diagnosed with cancer in low-middle-income countries are malnourished, while in paediatric oncology units (POUs) in Africa, less than half had a dedicated dietician, and only a third undertook routine nutritional assessment. Newly diagnosed children with cancer were longitudinally assessed for nutritional status in South Africa, including micronutrient assessment at diagnosis. The majority of the 320 children were well-nourished at diagnosis, while less than 15% had either stunting (14.3%), underweight (11.6%), wasting (8.1%), while a quarter (24.3%) had moderate acute malnutrition (MAM). Girls were more prone to being underweight (12.2% versus 4.5%; P = 0.027), while children five years and older had a higher prevalence of MAM (33.5% versus 14.5%; P < 0.001), with significant improvement six months after diagnosis (P < 0.001). Stunting was significantly associated with poor overall survival one year after a cancer diagnosis (HR 1.9; 95% CI 1.1, 3.3; P = 0.029). Nearly a third (27.8%) of patients had a high poverty risk that was significantly associated with stunting (P = 0.009), food insecurity (P < 0.001), and residential province (P < 0.001). Most children lived in households with a high risk of food insecurity (80%) and had an increased odds ratio for treatment abandonment (OR 4.5; 95% CI 1.0; 19.4; P = 0.045) and hazard for death (HR 3.2; 95% CI 1.02, 9.9; P = 0.046) compared to those with food security. Of 261 patients assessed for micronutrient status in two POUs, half had iron deficiency (47.6%), a third Vit A (30.6%), Vit D (32.6%), or folate (29.7%) deficiencies. There were significant associations between MAM and low levels of Vit A (48.4%; P = 0.005), Vit B12 (29.6%; P < 0.001), and folate (47.3%; P = 0.003). Male patients (40.9%; P = 0.004) and those with wasting (63.6%;P < 0.001) are associated with Vit D deficiency. Folate deficiency is significantly associated with children five years and older (39.8%; P = 0.002), residing in provinces Mpumalanga (40.9%) and Gauteng (31.5%) (P = 0.032); food insecurity (46,3%; P < 0.001), or haematological malignancy (41.4%; P = 0.004). The South African-adapted childhood cancer-specific nutritional algorithm was implemented in an intervention group versus a control group that received standard nutritional support protocol. The implementation of the algorithm led to a significant improvement in nutritional status for the malnourished patients in the intervention group, while it was insignificant for the control group. Determining socio-economic status and micronutrients at childhood cancer diagnosis in South Africa is crucial to plan appropriate nutritional interventions. Of note, stunting is associated with a poor one-year overall survival. The South African-developed algorithm successfully managed children with malnutrition at cancer diagnosis.
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    Clinical predictors of pulmonary embolism in pregnancy and immediate postpartum period: a retrospective, analytical study
    (Stellenbosch : Stellenbosch University, 2022, 2022-12) Sheehama, Ilona Ndapewa; Botha, Matthys Hendrik; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. Obstetrics and Gynaecology.
    ENGLISH ABSTRACT: Background Although pulmonary embolism (PE) is one of the leading causes of death in pregnancy and postpartum, it has low risk of adverse outcome if diagnosed early and treated appropriately. Ventilation-perfusion scanning (VQ scan) or computed tomography pulmonary angiogram (CTPA) are widely used to confirm or diagnose PE, however it carries risks to the mother and the fetus. Up to date, there is no validated clinical predicting tool that can be used in pregnancy and postpartum, thus clinicians face a challenge when suspecting PE in pregnancy and postpartum. Furthermore, the lack of medical resources in low resource environments contributes to the delay of investigations and diagnosis of PE. This study aimed to describe clinical markers for suspicious PE amongst pregnant mothers and immediate postpartum and to design a practical, clinical tool for accurate diagnosis of PE peripartum in our population. Methods The study was performed as a retrospective and analytical study over a period of four months, in the Obstetric Unit at Tygerberg Academic Hospital. The files (total 100) of the patients who were suspected of having PE and underwent imaging (VQ scan or CTPA) were retrospectively evaluated (ECM) to see if there was an association between clinical presentation and PE. All obstetric patients who were imaged for suspected PE, antenatal and immediate postpartum admitted to F2, C2A, OCCU, J2, J4 and J5 were included but not any patients already known with PE or varicose thrombosis. Results There was a statistically significant (P <0.05) association between PE occurrence and ten assessed factors (surgery in <4/52, immobilization >3/7, SOB, hemoptysis, sudden onset of pleuritic chest pain, respiratory alkalosis, sinus tachycardia, deep S1, Q3/T3 and HIV). Conclusion The researcher designed a clinical PE predicting tool that may be used in pregnancy and postpartum.
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    Non-invasive cardiac output monitoring in preterm neonates
    (Stellenbosch : Stellenbosch University, 2021-12) Van Wyk, Lizelle; Smith, Johan; De Boode, Willem-Pieter; Lawrenson, John; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
    ENGLISH ABSTRACT: Neonatal hemodynamic compromise is linked to numerous adverse neonatal outcomes. Objective, comprehensive, continuous hemodynamic monitoring of the systemic circulation, in conjunction with the pulmonary system, is required to timeously intervene and improve outcomes. Non-invasive cardiac output monitoring utilising bioreactance, a specific type of thoracic electrical biosensing technology (TEBT), may offer such a solution. The overall aim of this research was to determine the use of bioreactance as a comprehensive, non-invasive cardiac output monitor in preterm neonates (<37 weeks). Research aims included determining (1) agreement (bias and precision) and (2) trending ability of bioreactance. Further aims were to determine the use of bioreactance in monitoring hemodynamic parameters and thoracic fluid content in the transitional period (first 72 hours of life) and during respiratory support in preterm neonates. In a prospective, observational, longitudinal cohort study, the agreement (accuracy and precision) of bioreactance (BR), as compared to transthoracic echocardiography (TTE), for estimating cardiac output (CO) and stroke volume (SV) in a cohort of stable preterm neonates during the transitional period, was investigated. Bland Altman analyses showed a high bias, indicating poor accuracy, and wide limits of agreement, indicating poor precision, of BR as compared to TTE. A high percentage error indicated non- interchangeability of BR with TTE. Bias was shown to be affected by gestational age, birth weight, continuous positive airway pressure (CPAP), patent ductus arteriosus (PDA) and CO category. Despite a new technology’s inaccuracy and lack of absolute number agreement, it could possibly be a valuable trending monitor, if reference values were known. In the same cohort, the average values for BR-derived hemodynamic parameters (heart rate ( HR), blood pressure ( BP), SV, CO, total peripheral resistance ( TPR)) w ere described. All parameters were associated with postnatal age. Changes were in line with expected transitional changes, as described in the literature. BR may therefore be valuable to monitor the transitional period in preterm neonates. In continued accuracy analysis, the ability of BR, as compared to TTE, to track temporal changes in SV and CO was investigated. Four-quadrant and polar plots were used to assess BR trending ability. Concordance rate was lower than the accepted benchmarks, when using a 5% and 10% exclusion zone. Angular bias was high, radial limits were wide and radial concordance was poor; indicating a poor trending ability. Trending parameters were significantly associated with postnatal age, PDA, and CO category but not gestational age, birth weight or CPAP. BR, as compared to TTE, does not provide good trending analysis of CO and SV and should be used with caution in neonatology to direct therapeutic decisions. A narrative systematic review was performed to determine the agreement and trending ability of electrical biosensing technology (EBT) in neonates, including the current research. Only thoracic EBT studies, with TTE as comparator, were available for inclusion, up to December 2020. High heterogeneity was apparent in the eligible studies, due to varying gestational and chronological ages, birth weight, disease states, ventilation requirements, inotropic support and surgical intervention, which made meta-analysis impractical. Only agreement studies were available with no studies reporting trending analysis. Effect direction plots were used to report outcome measures (bias, percentage error). Overall, most studies showed that EBT was not interchangeable with TTE. Results remained similar in sub-analyses for preterm vs term neonatal populations, different respiratory support modes, cardiac anomalies and type of TEBT technology. In a post hoc analysis of the cohort study, BR-derived thoracic fluid content (TFC) parameters were described. TFC, another hemodynamic parameter, may be able to identify pulmonary fluid overload states, that may compromise cardiac function or be the consequence of cardiac dysfunction. Absolute TFC and cumulative TFC change from baseline (TFC and TFCd0, respectively) decreased over the first 72 hours of life. Both TFC and TFCd0 showed significant associations with clinical variables (gestational age, postnatal age, respiratory support mode). Sub-analyses according to respiratory support type and a pre-and post -intervention analysis was performed. TFC and TFCd0 showed significant pre- and post-intervention differences between respiratory intervention groups (CPAP and CPAP+surfactant). Neither TFC nor TFCd0 were associated with PDA in the transitional period. TFC and TFCd0 may offer the ability to monitor lung fluid during the transitional period in preterm neonates. In c onclusion, the agreement and trending of bioreactance in preterm neonates in the transitional period is questionable. Numerous physiological and interventional parameters influence this. However, on an individual level, BR may be able to monitor hemodynamic parameters, as parameters showed changes in the same direction as described in transitional physiology. Currently, bioreactance should be used with caution in the neonatal population to dictate therapeutic interventions. More research is required before bioreactance can be used at the bedside to replace transthoracic echocardiography.
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    Tuberculosis-associated mortality in South Africa: longitudinal trends and the impact of health system interventions
    (Stellenbosch : Stellenbosch University, 2021-03) Osman, Muhammad; Hesseling, Anneke Catharina; Naidoo, Prenavum; Welte, Alex; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
    ENGLISH ABSTRACT: Tuberculosis (TB) is estimated to have infected a quarter of the world’s population. In 2019, it was estimated that 10 million people developed TB globally and that the treatment coverage was 71%. In South Africa, approximately 360,000 people developed TB in 2019 with an estimated treatment coverage of 58%. Human immunodeficiency virus (HIV) is one of the most important drivers of TB, especially in sub-Saharan Africa. Of the estimated 38 million people living with HIV globally, 7.5 million (20%) were in South Africa. People living with HIV are more likely to develop TB disease and TB is one of the leading causes of death among people living with HIV. Among the estimated 1.4 million TB deaths in 2019; 59,000 occurred in South Africa. This estimate of mortality includes any death, regardless of the cause, occurring before or during antituberculosis treatment, and does not include TB-related deaths that occurred after the successful completion of treatment. TB reporting in South Africa is based on data captured in TB treatment registers and there are no routine estimates for TB-associated mortality before or after TB treatment. I used the onion model and the TB care cascade frameworks, to evaluate TB-associated mortality during, before and after TB treatment. Through a series of four interlinked studies, I investigated TB-associated mortality during TB treatment for adults and in children. I showed that mortality in South Africa decreased from 11% in 2009 to 8% in 2016 in adults, and from 3.3% in 2007 to 1.9% in 2016 in children and adolescents. I demonstrated that young children, older adolescents, the oldest adults, males, and people living with HIV (especially those with the lowest CD4 counts) were at highest risk of mortality during TB treatment whilst antiretroviral therapy (ART) had a protective effect. I also showed how this differs by HIV status and demonstrated that in people living with HIV, younger adult females have the greatest risk of mortality. I collected data for two studies to evaluate mortality before TB treatment. In the first, I reported a TB prevalence of 8% in people who died suddenly and unexpectedly; more than 90% had undiagnosed TB. I demonstrated multiple missed opportunities for TB screening and testing in these individuals. Sentinel surveillance for TB in this group could be an important indicator of TB control efforts. In the second study, I reported initial loss to follow up (ILTFU) of 20% in TB patients in 2 sub-districts of Cape Town among whom 17% had died. Although hospitals accounted for 25% of TB diagnoses, they contributed to 55% of patients with ILTFU and to 85% of the mortality in this group. This study demonstrates the need for earlier case-finding to reduce mortality and the value of including hospitals in routine TB reporting. Given the exclusion of mortality after TB treatment from the current definition of TB- deaths and the recognition of the burden of post-TB lung health, I conducted a study in Cape Town to assess TB patients who had successfully completed TB treatment. I showed the complexity of tracing these individuals. In the sample of adults located, I reported a high burden of respiratory symptoms and 6% had recurrent TB. The mortality rate following the successful completion of TB treatment was 2.5 deaths per 100 person years with a standardised mortality ratio of 4 compared to the general population. This highlights the need for ongoing care, post TB treatment completion. In this dissertation I documented the key health system changes in the public sector in South Africa and the changes in TB-associated mortality over time. Finally, I attempted to collate the findings of TB-associated mortality during, before and after TB treatment in the context of losses along the TB care cascade. This dissertation provides novel insights into TB-associated mortality in South Africa. I propose additional strategies to improve mortality estimates and to reduce TB-associated mortality in South Africa.
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    Improving early diagnosis and referrals to life-saving care for children with cancer in Cameroon
    (Stellenbosch : Stellenbosch University, 2021-03) Afungchwi, Glenn Mbah; Kruger, Mariana; Hesseling, Peter Bernard; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
    ENGLISH ABSTRACT: Childhood cancer is curable, but survival rates in low- and middle-income countries (LMICs), especially sub-Saharan Africa, are generally low. In 2018, the International Society of Paediatric Oncology (SIOP) and the World Health Organization (WHO) launched an initiative to improve childhood cancer survival to 60% by 2030 globally. As the majority of children with cancer live in LMICs, the emphasis should be on initiatives to improve survival in these countries. This PhD dissertation has investigated the incidence of childhood cancer in Northwest Cameroon, how to improve early diagnosis of children with cancer and the role of socioeconomic support of families with a child with cancer in Cameroon. Chapter 2 of this dissertation is a literature review, documenting the management of childhood cancer in Africa for the period 2014 to 2018. As part of a twinning programme between Stellenbosch University and the Cameroon Baptist Convention Health Services established in 2003, a hospital-based childhood cancer registry was prospectively analysed to determine the childhood cancer burden in Northwest Cameroon between 2004 and 2015 and is reported on in Chapter 3. Burkitt lymphoma was the most common diagnosis, followed by nephroblastoma and retinoblastoma, but Burkitt lymphoma diagnosis has decreased over time, probably due to the improvement in diagnosis of other childhood cancers. The registry data is useful to plan improved clinical services and may assist in future with the development of a population-based childhood cancer registry in Cameroon. To improve early diagnosis and referral of children with suspected cancers, a nurse-led training programme was conducted in six health districts of Northwest Cameroon with the support of the Sanofi Espoir Foundation’s My Child Matters programme. This low-cost training programme improved knowledge essential for early recognition of childhood cancer signs and could be replicated in other low-income settings for improved early diagnosis of childhood cancer (Chapter 4). The next step was to investigate the destitution level through a survey of families with children with Burkitt lymphoma and the association with adherence to treatment. Destitution level (measured by socioeconomic circumstances) did not affect adherence to treatment or follow-up for these children, probably due to the charity-driven financial support with regard to accommodation, food parcels and transport funding. However, survival rate was lower for children in single-mother households, which indicated the need for a more individualised model of support-based care for such single-parent families (Chapter 5).As traditional and complementary medicine (T&CM) use was common in Cameroon, further investigation was carried out to determine the use first in families with children with Burkitt lymphoma and thereafter in families with children across the spectrum of cancer. The initial study was done by the health care team with potential nondisclosure bias but found significant use of T&CM (Chapter 6a). The follow-up study therefore involved interviewers not part of the health care team to minimise nondisclosure bias. The majority of families of children with cancer had used (T&CM) before diagnosis while only a quarter of families had used T&CM after diagnosis (Chapter 6b). The use of T&CM resulted in worsening cancer symptoms and was financially costly to families. Half of the parents/guardians were not willing to disclose the use of T&CM to their treating health care team. A final step was to examine the development of paediatric oncology services in Cameroon over the last 20 years. Treatment programmes were developed largely with the help of international twinning programmes and support from charities as there was no financial support from the state (Chapter 7). Over the period, childhood cancer survival improved and staff capacity for the management of childhood cancer was established.This dissertation has provided local evidence of successful management of childhood cancer in Cameroon with suggestions regarding feasible actions necessary to achieve 60% childhood cancer survival by 2030 in line with the WHO-SIOP initiative.