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.
Late effects of childhood cancer and – treatment in a South African cohort
(Stellenbosch : Stellenbosch University, 2023-03) Van Zyl, Anel; Kruger, Mariana; Rogers, Paul C; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
ENGLISH ABSTRACT: Survival rates for childhood cancer have increased dramatically over the last few decades. Unfortunately, cure for childhood cancer survivors (CCSs) often comes at a cost. Most CCSs will develop at least one late effect or complication of the previous cancer or its treatment, potentially negatively impacting their health-related quality of life (HRQoL). Therefore, long-term follow-up (LTFU) care is necessary after treatment completion. LTFU care is established in most high-income countries (HICs) but is inadequate in most low- and middle-income countries (LMICs) due to limited resources. Little information on LTFU care for CCSs in South Africa is available, and no structured national LTFU programme exists. This dissertation aimed to investigate global and local LTFU care models and practices, document physical and psychological late effects in a South African CCS cohort, determine their HRQoL, describe their healthcare engagement patterns, and ultimately propose an appropriate LTFU care model for South Africa. A scoping review of LTFU care delivery in HICs and LMICs found that the most commonly used LTFU care model in LMICs was the cancer-centre-based model (the cancer centre provided all LTFU services). (Chapter 2) The community-based and shared care models (care divided between the cancer centre and healthcare partners at secondary or primary healthcare institutions or general practitioners) were increasingly used. A survivorship care plan was crucial for the success of a shared care model. Barriers to LTFU care in LMICs included a lack of trained staff and time, transport problems, insufficient funding, a lack of awareness concerning late effects among CCSs, and inadequate transitioning of care. In some LMICs, non-profit organisations provided funding for LTFU clinics and transportation. A risk-based LTFU stratification model where CCSs with a higher risk for late effects attended the cancer centre annually and those with a lower risk attended a community centre less frequently lessened the burden on the healthcare systems with increased adherence. A shared care, risk stratified LTFU programme with local LTFU guidelines would suit the South African healthcare system and environment. Subsequently, we surveyed local paediatric oncologists’ perceived knowledge regarding LTFU care and the current status of local LTFU care. (Chapter 3) Almost all participants regarded LTFU care and a national LTFU programme as important. However, this research highlighted inadequacies in the LTFU care for CCSs in South Africa, including a lack of formal training in and knowledge of LTFU care, as well as inadequate communication about potential late effects with CCSs. Only half of the paediatric oncologists used LTFU guidelines, and most adjusted them due to service constraints. Paediatric oncologists provided most of the LTFU care, while almost half successfully practiced a shared care model. The research confirmed the need for local LTFU guidelines to guide paediatric oncologists and other healthcare providers in the provision of LTFU care to CCS. We conducted a prospective cross-sectional analytic study to document all late effects in a CCS cohort at Tygerberg Hospital. (Chapter 4) One hundred and sixty CCSs attended a physical LTFU assessment and had appropriate surveillance special investigations. A higher proportion (91.3%) of CCSs compared to similar publications had at least one late effect. Most late effects were mild to moderate in severity. Common late effects were gastrointestinal, metabolic, haematological, musculoskeletal, and neurological disorders. Significant risk factors for late effects included cancer diagnosis, chemotherapy intensity, and radiotherapy. The cohort exhibited poor school performance, while their nutritional and socio-economic status worsened from diagnosis to study visit. This study confirmed a high prevalence of late effects among this South African cohort of CCSs. The worsening socio-economic circumstances might influence adherence to LTFU care. A formal LTFU programme will improve the early identification of and intervention for late effects in South African CCSs, which can improve outcomes. We investigated the level of psychological distress in adult CCSs. (Chapter 5) Forty participants completed the Brief Symptom Inventory-18 instrument for self-reported symptoms. We compared results utilising different case rules (Global Severity Index (GSI) T scores of ≥ 50, ≥ 57, and ≥ 63) for the identification of psychological distress. A GSI T score of ≥ 63 identified only 10% of survivors with psychological distress; a GSI T score of ≥ 57 identified 32.5%, and a GSI T score of ≥ 50 identified 45%. Significant risk factors were radiotherapy, the presence of more than six late effects, the severity of late effects, and a follow-up period of 11-20 years. The study revealed higher levels of psychological distress for this cohort utilising the GSI T score ≥ 50 and ≥ 57 case rules than reported in the literature. It underscored the importance of formal screening for psychological distress via a recognised instrument during LTFU. We also performed a pilot study to investigate a South African CCS cohort's HRQoL. (Chapter 6) CCSs, at least five years after diagnosis, completed the Minneapolis-Manchester Quality of Life adolescent- and adult forms. The age at the study visit and the number and severity of late effects were significantly associated with a poor overall HRQoL. Female sex was a risk factor for poorer psychological functioning. Compared to the adolescent-form cohort, the adult-form cohort had poorer psychological and social functioning and a more inferior body image. One lower stratum of socio-economic status was significantly associated with a more inferior body image and outlook on life. This study identified specific subsets of CCSs that have poor HRQoL. CCSs should be screened for HRQoL to ensure those needing psychological support can access such interventions. The last research component was a linkage analysis study to investigate the healthcare engagement patterns, late effects, and chronic diseases of the CCSs who could not attend physical LTFU assessments or were not contactable. (Chapter 7) These CCSs mainly attended tertiary- and primary-level institutions. A diagnosis at under four years of age, female sex, a cancer diagnosis of leukaemia, treatment with chemotherapy only, and a follow-up period of 16-25 years were associated with the highest number of healthcare visits. The most documented healthcare problems were infections and haematological, neurological, gastrointestinal, dermatological, and endocrinological abnormalities. Brain tumour survivors had the highest risk for healthcare visits at tertiary-level institutions and clinical abnormalities. Older survivors visited healthcare institutions more often. However, as the follow-up period increased, the healthcare visits decreased. This research provided valuable data about the healthcare use patterns of local CCSs. It highlighted the importance of strategies to retain CCSs in LTFU care. This dissertation provided novel and crucial data about the late effects of a CCS cohort in South Africa. We suggest implementing a risk-based shared care national LTFU programme with local LTFU guidelines to ensure sustainable and equitable LTFU care for all CCSs in South Africa. (Chapter 8). The provision of a survivorship care plan and adequate transitioning of healthcare is essential for success. A novel score-based LTFU risk stratification model that incorporates the number and severity of late effects, as well as the level of psychological distress and HRQoL, will facilitate a holistic approach to LTFU care and more accurate identification of CCSs.
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.
A critical interrogation of the acceptability of antituberculosis treatment in caregivers, children, and adolescents in the Western Cape, South Africa
(Stellenbosch : Stellenbosch University, 2022-12) Wademan, Dillon Timothy; Hoddinott, Graeme; Reis, Ria; Reynolds, Lindsey; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
ANGLISH ABSTRACT: Children often experience greater complexity and challenges both in terms of TB diagnosis and treatment. Although great strides have been made to reduce the length and complexity of treatment for both drug susceptible- (DS) and drug resistant (DR)-TB, daily preparation and administration to children remains challenging, with treatment for DR-TB being more complex to prepare, administer and adhere to. Challenges involved in treatment and care for children with TB can have lasting negative impacts on their overall psychological, social, and economic wellbeing. South Africa accounted for 3.3% of all estimated incident TB cases worldwide in 2021. Here, household, socio-economic, and environmental conditions influence treatment management decisions. This project interrogates the acceptability of antituberculosis treatment (ATT) among caregivers and children in the Western Cape, South Africa. For this project, ‘ATT’ includes the drugs and any additional treatment related processes involved to prevent or cure TB. The predominant definition of treatment acceptability refers to the overall ability of the children and caregivers to use the treatment as intended. Most existing measures and studies use palatability, ease of use, and adherence as proxy measures of treatment acceptability. However, other factors including socio-economic circumstances, health services access, and stigma, may also influence the overall acceptability of ATT. This project describes the historical emergence of increasing interest and investment in new, ‘child-friendly’ drugs towards improving the overall acceptability of ATT among children and their caregivers. Through two empirically driven manuscripts, I describe how broader psychosocial, economic, and contextual factors influence caregivers’ and children’s acceptability of ATT. These data toward are drawn from three qualitative sub-studies of ATT trials at the Desmond Tutu TB Centre (DTTC). These studies are, the Shorter Treatment for Minimal TB in children (SHINE) trial; Tuberculosis Child Multidrug-resistant Preventive Therapy (TB-CHAMP) trial; and the Optimizing and operationalizing paediatric drug-resistant tuberculosis (MDRPK2) study. These data comprise semi structured interviews with children and their caregivers. Children (aged ≤17) and their caregivers (aged ≥18) were recruited to the qualitative sub-studies from the parent trials. The findings suggest that while palatability, adverse effects, and health services access, remain a concern for children and their caregivers, psychosocial, economic, and other contextual factors should be considered part of determining the overall acceptability of ATT. The final manuscript proposes an early-stage conceptual framework to measure the many factors that may influence the acceptability of treatment ATT among children and their caregivers. The conceptual framework presents an opportunity to identify key obstacles within households, communities, and healthcare systems to optimise the degree of fit between patients’ needs and available treatment for children with TB. It provides the first steps towards a global standard against which novel treatment strategies could be measured to determine overall TB treatment acceptability. This project contributes to this emerging field of research by providing evidence of the perceived impact of contextual factors on the acceptability of ATT among children and their caregivers. This project provides a conceptual framework with which future researchers can better determine what factors influence the acceptability of ATT among children and their caregivers.
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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