Paediatrics (RCH) - Theses

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    Oral narrative skills of 5- to 7-year-old Aboriginal children growing up in South Australia
    Cahir, Petrea Katrina ( 2023-07)
    Narrative discourse provides rich cultural and linguistic insights into worldviews, language use and development. This study—embedded within a prospective, longitudinal study of Aboriginal children and their families living in urban, regional and remote areas of South Australia—aimed to describe Aboriginal children’s fictional narrative development in their early school years (aged 5–7-years). Aboriginal researchers recorded children’s stories (N = 72) in response to the picture book Frog, where are you? (Mayer, 1969). Across the total sample, the children told stories using a diverse range of dialectal features of Aboriginal English(es), illustrating a diverse range of language repertoires. The first aim of this research was to describe the ways children organise story events and plot structure in fictional storytelling. Macrostructural elements of narratives were analysed, including plot components, goal-oriented frameworks and story event inclusion. The second aim was to describe patterns and variations in children’s use of temporal expressions (grammatical and lexical) and their functions to tell cohesive stories. Within-sample comparisons across ages and the areas where children lived (major city, regional and remote communities) were made. Drawing on maternal and primary caregiver questionnaire data, the third aim of the research was to explore relationships between the narrative abilities and maternal, social family or household factors. The study prioritised culturally-informed research processes and took a data-driven approach to analysis. Across the narrative measures, variability of skills and approaches to storytelling were apparent, but developmental patterns were also identified. Analysis of macrostructural elements of narrative samples identified a significant, positive age-related increase in skills. On average, children's stories did not differ between geographical areas (metropolitan and regional/remote). Following comprehensive, dialect-specific coding of verbal morphology, developmental progression of temporal cohesion skills across the total sample was similarly identified, but this did not differ significantly between age groups. Consistent with other studies of language and narrative development, findings suggest wide variation amongst children in the early years of school. Individual differences, known to exist more broadly in language development, were identified. Some variance could be explained by the impact of social determinants (mother’s employment and household income), but this requires replication with larger samples of families. Other factors (e.g., difficulties with cognition or language learning) were also considered as contributing factors to children’s narrative outcomes; however, the absence of additional developmental data limited the observations made. Additionally, differences based on observations not captured in the study-derived measure of narrative cohesion suggest children’s use of culturally-salient approaches to telling cohesive stories. Overall, this research—the first study of Aboriginal children’s storytelling in southeastern Australia and the largest of any fictional narrative study with Aboriginal children—systematically describes the variation of children’s development also observed in real-world contexts. The findings have important implications for culturally competent clinical and education practices, particularly emphasising the need to understand reasons for variability, which can potentially reduce the risk of misunderstandings and misjudgements in intercultural classroom and clinical settings. Further research, however, is needed to identify potential protective factors and vulnerabilities for Aboriginal children’s narrative development.
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    Urinary tract infection in children – changing the management paradigm so more children can be treated at home
    Scanlan, Barry Thomas ( 2023-07)
    Urinary tract infections (UTI) are a common reason for paediatric emergency department (ED) presentations. Although most children are successfully treated with oral antibiotics, approximately one-third receive intravenous (IV) antibiotics and hospital admission. However, there is limited evidence supporting these decisions, and consequently an opportunity to approach antibiotic use differently to potentially treat more children out of hospital. Guidelines recommend most patients can be treated with oral antibiotics, but the studies used to support these guidelines excluded several cohorts. The aims of this thesis were to investigate current UTI management, particularly use of antibiotics and Hospital-in-the-Home (HITH), to define which children actually need IV antibiotics, and to explore the feasibility of using shorter IV antibiotic durations. The initial study focused on use of HITH for IV antibiotics for UTI. The study found that 90% of patients successfully completed treatment without readmission to hospital, and none became severely unwell at home. However, HITH was underused, with only 8% of patients on IV antibiotics using this model. The study supports home IV antibiotics for selected UTI management. The next study used a wider lens, examining all current UTI management in ED and found little variation in antibiotic route, choice, and duration for lower UTIs and uncomplicated upper UTIs. However, complicated upper UTIs, where there is less evidence, showed more variation. No single feature reliably predicted use of IV antibiotics, but multiple complicating factors were associated with their initiation, suggesting they represent ‘red flags’ for clinicians. In the following study, clinicians were asked why they used IV antibiotics for UTI and admitted children to hospital. Although they had defined reasons for using IV, objective clinical evidence did not always support their reasons. The study hypothesised that multiple features lead to the decision to prescribe IV antibiotics and that these features may group together. Given the finding that multiple but not always the same features led to IV antibiotic initiation, the next study aimed to develop a clinical score to determine which children need IV antibiotics. The Melbourne RUPERT score was successfully developed and tested on patients with confirmed and probable UTI. Using six clinical features, the score is straightforward, easily attainable, reproducible and aids consistent stratification of patients to determine route of initial antibiotic treatment. Finally, using outcomes and learnings from the preceding studies, a randomised control trial protocol was developed. This trial aims to investigate whether an ultra-short IV duration (1 day) is non-inferior to the standard duration for children requiring IV antibiotics. If a single daily dose of IV antibiotics followed by oral antibiotics proves sufficient, patients could be discharged home from the ED on oral antibiotics, eliminating the need for hospital admission. In questioning whether more children with UTI could be treated out of hospital, this thesis found that indeed they can, through delivering IV antibiotics at home, treating more children with oral antibiotics, and investigating an identified practice of earlier switch from IV to oral. This has the potential for major impacts on patient care and hospital sustainability.
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    Investigating the molecular basis of brain malformations causing severe infantile epilepsies
    Coleman, Matthew John ( 2023-08)
    Malformations of cortical development (MCD) encompass a wide spectrum of conditions that result from abnormal brain development, including polymicrogyria, periventricular nodular heterotopia and focal cortical dysplasia. MCD affect ~1 in 2,500 children and can result in epilepsy, developmental delay and cerebral palsy. Infantile epileptic spasms syndrome (IESS) is one of the most common forms of severe epilepsy of infancy and MCD are observed in ~50% of children with IESS. It is thought that the majority of cases of IESS and MCD have an underlying genetic cause. Although multiple molecular pathways have been identified, ~60% of cases still lack a genetic diagnosis after standard clinical diagnostic testing. Genetic diagnoses are important for prognosis, diagnostic testing, genetic counselling and precision medicine. Recent advances in genetic technologies allow for rapid, in-depth interrogation of the molecular mechanisms underlying MCD formation. The hypotheses of this thesis are that the application of high-resolution genomic technologies will facilitate a better understanding of the genetic causes of IESS with MCD and that functional characterisation of genes of interest will assist to identify crucial molecular pathways in the normal development and function of the developing brain. The primary research aims of this project are: to investigate the genetic landscape of IESS due to MCD by utilising brain tissue studies; to develop a deeper understanding of the molecular basis and phenotypic classifiers involved in the pathogenesis of brain somatic SLC35A2 variation and its relationship to mild malformation of oligodendroglial hyperplasia in epilepsy (MOGHE); and to identify molecular mechanisms and biomarkers of MOGHE. The genetic basis of IESS due to MCD was identified in 47/59 (80%) individuals. Germline pathogenic variants were identified in 27/59 (46%) individuals in TSC2 (n=19), DEPDC5 (2), CDKL5 (2), COL4A1 and 6p25.2 deletion (1), NPRL3 (1), FGFR1 (1) and TSC1 (1). Pathogenic brain somatic variants were identified in 21/59 (36%) cases, in SLC35A2 (n=9), PIK3CA (3), MTOR (2), TSC2 (2), AKT3 (2), OFD1 (1), TSC1 (1) and DEPDC5 (1). This included one individual with a two-hit DEPDC5 diagnosis, with a germline DEPDC5 variant and a somatic DEPDC5 variant. Multidisciplinary tools and integrated diagnosis review identified all nine individuals with SLC35A2 variants as having mild malformation of cortical development with oligodendroglial hypoplasia in epilepsy (MOGHE). Multi-omic analysis of MOGHE tissue using single nuclei RNA-sequencing (snRNA-seq) and Tandem Mass Tag 16pro liquid chromatography–mass spectrometry (LC-MS/MS) showed that neurogenesis, neuron projection development, axo-dendritic development and neuron differentiation are dysregulated in MOGHE. snRNA-seq analysis identified oligodendrocyte progenitor cells (OPCs) and dividing oligodendrocyte progenitor cells (cOPCs) as the primary cells exhibiting aberrant expression profiles in lesional MOGHE tissues. ACTB, GNG7, MAP4, NEFL, SEMA3E and SOD1 were identified as potential biomarkers in MOGHE and may serve as disease biomarkers or druggable targets in the future. The findings of this thesis contribute to the knowledge of the genetic landscape of paediatric brain malformations and severe epilepsies of infancy and broaden the understanding of cortical malformation development and epileptogenesis.
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    We could do more, but should we? The approach to decisions about life-prolonging treatments for children with life-limiting conditions
    Vemuri, Sidharth ( 2023-05)
    Children with life-limiting conditions are anticipated to have episodes of clinical deterioration in their health. These episodes of deterioration can be significant and may result in the child’s death. During these episodes, decisions about whether to embark on treatments designed to prolong life arise. These treatments involve intensive care therapies, such as intubation and mechanical ventilation, and resuscitative measures. Decision making about these treatments for children with life-limiting conditions commonly occurs between the child’s paediatrician and their parents. This is because the child often lacks developmental capacity to participate in decision making for themselves. Making decisions about life-prolonging treatments, otherwise known as end-of-life decision making, is often viewed with significant trepidation by paediatricians because of the gravity and emotional nature of these decisions. Little is known about how these decisions are made in practice. Despite this gap in knowledge, consensus guidelines in middle- to high-income countries recommend the practice of shared decision making and advance care planning. Shared decision making and advance care planning are concepts that emerge in the care of a decisionally competent adult patient, to preserve and respect their autonomy in decision making. These concepts are poorly understood in the paediatric context where decisions are being made for the child rather than with the child. This thesis explores how paediatricians approach end-of-life decision making for children with life-limiting conditions. This exploration adopts an interpretivist approach which that assumes that a paediatrician’s experience of end-of-life decision making will shape their practice. To achieve this, this thesis draws on two qualitative studies involving semi-structured interviews. The first involves paediatricians primed by a paper-based vignette; the second involves paediatricians and parent-actors primed by a clinical simulation. Development of the latter study was supported by a scoping review of methodological literature. The overall findings were that paediatricians identified and valued a preparatory process of discussions with parents for end-of-life decision making for children with life-limiting conditions. Most paediatricians did not regard this preparation as advance care planning but considered it the practice of shared decision making. Despite reporting this practice as shared decision making, what paediatricians often described were physician-led decision-making approaches. Detail of how paediatricians work within and lead this preparatory process was revealed, with their overarching aim being to facilitate alignment of parental views with the paediatrician’s goals of care for the child. The mechanism by which paediatricians intend to achieve this by leading parents through this process of discussion in preparation for end-of-life decision making was discovered; this mechanism has been termed ‘shepherding’. By developing understanding of paediatricians’ perspectives of the process of preparing for end-of-life decision making for children with life-limiting conditions, there is an increased awareness of the broader ethical landscape in which end-of-life decision making occurs. This thesis makes the end-of-life decision making process for children with life-limiting conditions visible, providing a shared language that can facilitate consistency of practice and training, and future targeted research. Finally, this thesis contributes to knowledge about the role of simulation as a reliable and feasible option in qualitative research inquiry, which should encourage its use in future research of highly sensitive phenomena.
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    Quantifying oedema in children in intensive care
    Gelbart, Ben ( 2023-07)
    Oedema is the accumulation of fluid in tissues and an important clinical sign in the management of critically ill children. It indicates that fluid extravasation from the intravascular to the interstitial space has exceeded physiological clearance mechanisms. The initial mechanistic descriptions in the 19th and 20th centuries still hold true, but there is now greater understanding of the pathophysiology of diseases and interventions that cause oedema, particularly regarding the role of endothelial injury and dysfunction. Oedema is clinically recognisable by clinicians; however, its clinical assessment is inexact and therefore its relevance poorly understood. Positive fluid balance (or fluid accumulation) on the other hand, as measured by fluid balance charts, is a widely reported metric, measurable, and over the past two decades, numerous studies have reported its associated harm in critically ill children. Virtually no data exist regarding the outcomes associated with oedema. This is, at least in part, because standardised, validated methods for quantifying oedema do not exist. The overarching aims of this thesis focused on the development of methods for quantifying oedema and investigating their precision and validity. A prospective observational study in infants with congenital heart disease in intensive care was conducted in this regard. There are virtually no data on the clinical measurement of oedema and therefore the nature of this study is exploratory. The study investigated simple and novel techniques and investigated their validity as well as their relationships to important clinical outcomes such as vital organ oedema and organ dysfunction. This study was supported by preliminary pilot work to establish feasibility and safety of such methods and a retrospective study which investigated the associated outcomes of fluid accumulation measured by fluid balance charts. This thesis addresses an important component of critical illness where a knowledge gap exists and the commonly utilised and reported metric, fluid balance, insufficiently defines fluid status during critical illness.
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    The Role of Maternal Serum Biomarkers in the Aetiology of Cerebral Palsy
    Peris, Monique Caroline ( 2023-02)
    Background CP affects 1 in 700 infants in Australia and is a major cause of physical disability in children. Long term psychological and financial impacts are associated with children with CP and their families. Despite its prevalence, limited effective prevention strategies exist due to the complex aetiology of CP, extensive timeframe over which injury can occur and diagnosis which is often delayed from the time of injury. The Australian Cerebral Palsy Register Report has identified that an estimated 94% of cases of cerebral palsy originate in the antenatal and perinatal period, which draws attention to this important time in the developing brain. Routine maternal serum screening testing in Victoria currently encompasses combined testing of biomarkers to predict the likelihood of congenital and chromosomal anomalies. PAPP-A, hCG, AFP, uE3 and inhibin are well recognised markers of placental integrity used in antenatal testing. Adverse pregnancy outcomes associated with placental dysfunction are also known to increase the risk of CP. Aims and Methods The aims of this research were twofold. Firstly, to determine if first and second trimester biomarkers used in current maternal serum screening are associated with pregnancies resulting in an infant with CP. Secondly, to evaluate what maternal serum biomarkers tell us about aetiological pathways of CP in the antenatal period. The methods used to investigate these aims were: 1. Data linkage between the Victorian Cerebral Palsy Register (VCPR) and Maternal Serum Screening service of the Victorian Clinical Genetics Service (VCGS) linking CP cases with their antenatal screening blood tests. Analysis of the association between CP cases and non CP controls using a retrospective case control study design and predictive analysis. 2. Systematic review of the role of hCG in pregnancy to determine how this biomarker contributes to understanding of aetiological classifications of CP in the antenatal period. Results Data linkage resulted in 435 first trimester and 129 second trimester CP cases who underwent maternal serum screening. Low first trimester levels of PAPP-A and beta-hCG and high second trimester levels of AFP and inhibin were associated with pregnancies that resulted in an infant with CP. Despite this all biomarkers showed poor predictive ability as a diagnostic test for CP. Abnormal biomarker levels were associated with adverse pregnancy outcomes known to increase the risk of CP such as prematurity, perinatal hypoxia-ischaemia and congenital anomalies. The systematic review found an association between placenta mediated pregnancy complications and hCG, highlighting the importance of placental biomarkers as markers of placental dysfunction and integrity. Conclusion First and second trimester biomarkers are associated with the subsequent development of CP, suggesting placental dysfunction as part of the causal pathways in these cases. Improving intervention and prevention relies on improving understanding of the role of the placenta in the aetiology of CP.
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    Investigation of approaches for handling missing data in complex epidemiological studies
    Middleton, Melissa ( 2023-04)
    Missing data are ubiquitous in epidemiological studies and multiple imputation (MI) and inverse probability weighting (IPW) are popular statistical tools to address this. Both approaches can reduce bias in the target effect estimate compared to the standard complete-case analysis, with MI also often improving precision. However, MI may result in biased target effect estimates if the imputation model is misspecified, particularly when imputing large amounts of missing information. Conversely, IPW may not be effective to handle missing data in a disorganised pattern across multiple variables. An alternative approach is to combine MI and IPW, where MI is used to handle small amounts of data missing across multiple variables, while IPW is used to address larger proportions of missingness. The aim of this thesis is to explore the use of MI in combination with IPW, including how best to implement a combined approach, and how it compares to either MI or IPW alone. Simulation and case studies are used to evaluate the approaches, motivated by two case studies considered within the Barwon Infant Study: a case-cohort study with a binary endpoint, and a longitudinal study investigating the effect of an exposure on an outcome measured at a given timepoint. In case-cohort studies, a large proportion of exposure data is missing ‘by design’ and is typically handled with IPW, while unintended missing confounder data are handled using MI. One key consideration of MI is that the imputation model should be compatible with the target analysis model, that is all features and variables of the analysis model should be considered in the imputation model. In the context of using a combined MI/IPW approach, this requires the weighting to be incorporated into the imputation model. There is currently a lack of guidance on how best to do this. It is also unclear whether MI or IPW alone may provide any benefit over a combined approach. In longitudinal studies, missing data is typically handled using MI, however, when there are large proportions of incomplete outcome data due to drop-out, it is unclear whether a combined MI/IPW approach may be preferrable. Within a combined approach, incomplete outcome data could be handled using IPW, while MI is used to handle incomplete covariates. It is unclear whether a combined MI/IPW approach offers any benefit over MI or IPW alone in this setting. The findings from this thesis suggest that in case-cohort studies with a binary endpoint, inclusion of the weights as a predictor in the imputation model when using a combined approach performed well suggesting that it may be sufficient for imputation model compatibility. Additionally, a combined MI/IPW approach provides relatively unbiased target parameter estimates and was preferable to an MI-only or IPW-only approach. In the longitudinal setting, there was no gain in terms of bias or precision when using a combined MI/IPW approach over MI-only, with both performing well. Given that MI-only is simpler to implement, this may be the preferrable approach in this context. The findings from this thesis provide guidance on the use of a combined MI/IPW approach in the context of case-cohort studies with binary outcomes and longitudinal studies estimating the effect of an exposure on an outcome measured at a given timepoint. They address a much-needed gap in the literature for handling missing data in complex epidemiological studies.
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    Safety of Bacille Calmette-Guérin vaccination and revaccination
    Villanueva, Paola ( 2022-12)
    Bacille Calmette-Guerin (BCG) vaccine, derived from live-attenuated Mycobacterium bovis, is commonly given as a single dose in infancy to protect against tuberculosis (TB) in high TB-prevalence settings. There is growing interest in BCG revaccination for the protection of adolescents and adults against TB. Increasing recognition of potential novel applications for BCG to protect against diseases other than TB also mean that BCG vaccination (and revaccination) may become increasingly used in broader age groups and settings. For these reasons, a more comprehensive and detailed understanding of the safety of BCG vaccination and revaccination, particularly in adults, is necessary to help inform public health policy. My PhD research aimed to evaluate the incidence and predictors of reactions (normal, accelerated and adverse) to BCG vaccination, the impact of revaccination on BCG reactions, and the clinical management of adverse reactions to the vaccine. These aims were investigated using active safety surveillance of BCG vaccination reactions within an international randomised controlled trial of nearly 7000 adult participants – the BRACE Trial (BCG vaccination to reduce the impact of COVID-19 in healthcare workers), as well as through two systematic reviews and a meta-analysis of BCG vaccination safety in children. My thesis comprises three sections characterising reactions following BCG vaccination and revaccination: (i) the normal reaction; (ii) accelerated reactions; and (iii) adverse events. The first section reports a cohort study to assess the prevalence, factors influencing formation and vaccinee perception of BCG scarring (normal BCG reaction) following vaccination and revaccination in adults. The second section includes a systematic review and meta-analysis to investigate the clinical significance of an accelerated BCG reaction in children, reporting an association with prior mycobacterial exposure. A cohort study is then presented that evaluated the incidence and clinical implications of an accelerated BCG reaction in asymptomatic adults in low and high TB-prevalence settings. The third section includes a systematic review of the management strategies for BCG-associated lymphadenitis and injection site abscess in children. This is followed by a cohort study to assess the incidence and risk factors (host immune- and vaccination-related) for BCG-associated lymphadenitis and injection site abscess in adults. An additional cohort study in adults assesses the safety of co-administration of BCG with the influenza vaccine. The overall incidence of local adverse events and serious adverse events in the BRACE trial is then described, as well as the impact of previous BCG vaccination on local injection site reactions. Overall, BCG revaccination in adults was associated with increased frequency of normal (scar), accelerated and local adverse reactions (injection site abscess and lymphadenitis), compared to receiving BCG for the first time. Younger age was also associated with increased frequency of normal and local adverse reactions. Similarly, female sex was associated with an increased frequency of normal reactions and lymphadenitis following BCG vaccination, as well as increased frequency of accelerated BCG reactions. Latent TB infection was found to predispose to an accelerated BCG reaction, but was not associated with injection site abscess. Nonetheless, regardless of prior BCG vaccination status, age or sex, the majority of reactions were mild in nature, localised to the injection site and resolved without intervention. In summary, the studies in my thesis indicate that BCG vaccination and revaccination have an acceptable safety profile in children and adults.
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    Exploring the investigation, diagnosis and clinical management of tree nut and peanut allergy in children
    Brettig, Timothy William ( 2023-03)
    By the age of one, 1 in 10 Australian children have developed a food allergy. Most people are aware of common allergens such as cow’s milk, egg, and peanut, but tree nut allergy is less recognised and researched despite having a prevalence similar to peanut allergy in older children. Peanut and tree nuts are responsible for the majority of fatal or near-fatal allergic reactions to food and with natural allergy resolution for peanut reported as 30%, and tree nuts collectively reported as 10%, a diagnosis of peanut or tree nut allergy carries a poor prognosis. Diagnosis of food allergy is not simple. Clinical history determines whether a clinician may perform a diagnostic test such as a skin prick test or blood test to determine the likelihood of allergy. If the result is not conclusive, then an oral food challenge (OFC), or medically supervised food introduction is required to achieve an accurate diagnosis. Whilst OFCs are the gold standard for diagnosis, they are time and labour intensive, expensive and put the individual at risk of severe allergic reaction, or anaphylaxis. They are also the ‘bottle-neck’ in the diagnostic process with limited access relative to the burden of food allergy assessments. With limited understanding of the accuracy of current diagnostic tools there is a real risk for over-diagnosis of tree nut and peanut allergy. This thesis aims to improve the diagnostic approach to tree nut and peanut allergy. It explores several areas involved in the diagnosis of tree nut and peanut allergy including describing the prevalence of cashew allergy and the diagnostic accuracy of currently used tests for specific tree nuts. It also explores the use of diagnostic algorithms as a method to improve diagnostic accuracy and reduce the need for OFCs in both modelled and ‘real world’ datasets for cashew and peanut allergy. The cost of these interventions is also assessed in the first economic evaluation for use of diagnostic algorithms in tree nut allergy diagnosis. Using the population-based EarlyNuts cohort (n=1933), I found the prevalence of cashew allergy in 1 year old infants to be 1.49%, with sensitisation (SPT result >/= 3mm) seen in 1.96%. Infants with eczema in the first year of life were more likely to be cashew allergic (adjusted odds ratio=5.75) and there was also an association between peanut allergy and cashew allergy (adjusted odds ratio=19.30). Cashew was introduced before 12 months of age in 25% of participants, which was low compared to other foods such as peanut. I have undertaken a systematic review of the accuracy of the current tests used in diagnosing tree nut allergy. This review highlighted that for some tree nuts, such as cashew or walnut, the accuracy of tests was reasonable, but many nuts lacked evidence about a conclusive diagnostic cut-off, increasing the likelihood of requiring an OFC for definitive diagnosis. Tests for cashew allergy were most accurate compared to other tree nuts, and newer blood tests, specifically IgE to the cashew component ana o 3, were superior to the commonly used method of a cashew skin prick test for diagnosis. To investigate this further, I combined and analysed global data from studies of patients with possible cashew allergy that had data on both test results and food challenge outcomes, demonstrating that using ana o 3 or a diagnostic algorithm incorporating sIgE to cashew followed by ana o 3 resulted in an 80% reduction in the need for an OFC to get a definitive diagnosis compared to skin prick testing alone. I performed a cost-comparison analysis comparing these approaches to skin prick testing alone (the current clinical practice standard in Australia) again using modelled data. This demonstrated a 46% cost reduction to the healthcare system. The final step of my PhD was to investigate the clinical and economic impact of a similar 2-step algorithm used in a large tertiary hospital allergy department for diagnosis of peanut allergy. This retrospective clinical audit (n=8826) demonstrated an uptake of the diagnostic algorithm of 41.95% of eligible presentations, which resulted in a 27.8% reduction in OFCs performed compared to using peanut SPT alone. I also demonstrated a 32% cost reduction as a result of implementing this pathway. The outcomes of my thesis can be directly translated into modifications of clinical practice resulting in significant clinical impact by achieving more accurate and timely clinical outcomes with fewer OFCs, improved safety for individuals and substantial cost reductions to the health system.
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    Towards timely screening and diagnosis of neonatal jaundice
    Thomas, Mercy ( 2023-04)
    ABSTRACT Neonatal jaundice remains one of the primary reasons for newborn hospital readmissions, despite the efforts to recognise at risk newborns before birth hospital discharge. Due to the increasing prevalence of early hospital discharge of neonates, community based screening, including appropriate point of care technology, is essential for the timely detection of jaundice. This thesis aimed to generate and compile evidence to advance the timely screening of neonatal jaundice in community settings. The thesis contains one review paper, a discussion paper and three research studies, each investigating aspects of the evidence required for advancing neonatal jaundice screening policy. The first study determined the rate and severity of jaundice readmissions to tertiary level neonatal services in Victoria. Medical records of newborns from four major metropolitan health services were retrospectively reviewed for April to September of three consecutive years 2018, 2019 and 2020. The overall incident rate of jaundice readmissions was high at 3.3%. While the rate of readmissions differed between hospitals, the percentage of newborns readmitted remained the same across the study period at most sites. A substantial number of newborns (11%) were readmitted with severe jaundice, and this presentation was similar across both the gestational age groups of 35 to 37+6 weeks and greater than or equal to 38 weeks newborns. Moreover, a significant proportion (37%) of newborns were readmitted earlier than usual (within three days of age) following discharge from the birth hospital. The second study assessed current screening practices, including the enablers and barriers to screening and opportunities to optimise neonatal jaundice screening in community settings. An anonymous, purpose-designed web-based (REDCap) survey was sent to maternal and child health (MCH) nurses who worked across the local government areas from metropolitan and regional Victoria, and to domiciliary midwives from two selected hospitals in Metropolitan Melbourne. The most common enablers were physical examination of newborns and discharge summaries from the birth hospital for MCH nurses, compared to years of experience, and jaundice screening documentation tools for domiciliary midwives. Common barriers included screening newborns with darker skin tones, communication difficulties among culturally and linguistically diverse families, and lack of point of care screening tools. Recommendations from this study include the need for point of care screening tools, optimising the screening process by providing parent and staff education, a standardised, evidence based practice guideline, and a timely streamlined handover process between birth services and MCH services. The third study investigated the possibility of developing a low cost point of care screening tool to aid in the onsite, real-time diagnosis of neonatal jaundice in community settings. New insights in transporters of bilirubin metabolism hypothesise that a proportion of bilirubin is excreted via the renal system. This study aimed to determine if unconjugated bilirubin, the key biomarker responsible for neonatal jaundice, could be measured in the urine of newborns. Urine samples of jaundiced (SBR greater than150 umol per Litre) newborns (n=22) were collected within the first 72 hours of life. Urine samples were analysed using two methods 1) High-performance liquid chromatography and 2) Liquid chromatography triple quadrupole mass spectrometry. The preliminary findings indicated the presence of unconjugated bilirubin in the urine of newborns but at low levels. While urine bilirubin could facilitate a less invasive jaundice screening method, the correction for urine concentration and correlation to serum bilirubin needs would need to be established before validating the diagnostic utility of urine bilirubin. The results of this project highlight the existing gaps in practice for the timely detection of neonatal jaundice in community settings, which can lead to avoidable hospital readmissions and severe cases of jaundice. The study emphasises the opportunity to enhance preventative strategies, including improving infant feeding practices, enhanced communication pathways between birth services and MCH services, implementing community-based screening protocols, and utilising point of care screening tools to improve newborn outcomes. These findings have important implications for public health policy, practice, and research. To ensure the successful implementation of these recommendations, an implementation framework is proposed involving collaboration among healthcare providers, policymakers, and researchers to develop guidelines, education resources and a communication pathway between birth services and MCH services to ensure optimal screening practices and timely diagnosis of neonatal jaundice.