Paediatrics (RCH) - Theses
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ItemAssessment of pulmonary function in childhood neuromuscular weakness( 2004)Children with neuromuscular weakness may have severe or progressive weakness that results in pulmonary restriction. Weakness can also result in spinal deformity that worsens the pulmonary restriction. Corrective spinal surgery carries significant respiratory risk. Accurate respiratory assessment is important for pre-operative risk assessment. Aims: 1) to evaluate the current clinical practice of pulmonary function testing and their role in respiratory assessment in children with neuromuscular weakness undergoing corrective spinal surgery and 2) to develop a precise method of predicting pulmonary function tests in children with neuromuscular weakness.
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ItemThe genetic control of neural crest development in early craniofacial morphogenesis( 2004-11)Craniofacial development requires orchestrated and complex interactions between multiple tissues of different origins. Cranial neural crest stem cells migrate from the dorsal neural tube into the frontonasal process and branchial arches where they ultimately form most of the skeletal structures and connective tissue of the craniofacial complex, as well as contributing neurons and glia to cranial ganglia. The timing and mechanism by which cranial neural crest cells progressively differentiate from multipotent stem cells into lineage restricted and terminally differentiating cell types has previously not been investigated. In addition, there are many deficits in our knowledge of the molecular controls regulating early development of neural crest cells within the branchial arches. Spatial and temporal changes in migratory and lineage potential in neural crest populations contributing to the developing first branchial arch and trigeminal ganglia were examined by back-transplanting cells from quail into chick embryos. Neural crest cells that had barely entered the first branchial arch had largely lost both the ability to localise to the trigeminal ganglia and neurogenic differentiation capacity but were still capable of long-distance migration. However, after a further 12 hours residence in the branchial arch, neural crest cells had lost long-distance migratory ability.
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ItemAn evaluation of the quality of different forms of early postoperative care in children following tonsillectomy( 2004)Introduction: The perioperative care of children has undergone a revolution in recent years with the introduction of day-case care. The introduction of clay-case care as an alternative to inpatient care has predominantly been for economic reasons. The care of children in hospital by their parents has been advocated for many years and came into vogue in the 19608 with the emergence of the Care-By-Parent-Unit (CBPU) movement. Whilst reportedly successful, this form of care was poorly evaluated and succumbed to the economic pressure that led to the introduction of day-case care. This thesis describes the introduction and evaluation of a CBPU in an attempt to identify the role of CBPU care for the immediate postoperative care of children in a major paediatric tertiary referral centre. Method: A randomised, controlled trial was performed comparing inpatient and CBPU care for the management of children following tonsillectomy. A non-randomised cohort of children undergoing day-case tonsillectomy was also included for comparison. The primary outc0l11e was the quality of clinical care assessed using a composite of five clinical outcomes. Secondary outcomes included the incidence of posthospitalisalion behavioural changes assessed using the Posthospitalisation Behavioural Questionnaire (PHBQ)), parental satisfaction, and the results of an economic analysis. Results: 288 children were assessed in the randomised comparison of inpatient and CBPU care. An additional 129 children were included in the day-case cohort. The results indicated that the CBPU offered a standard of clinical care at least equivalent to both inpatient and day-case care according to prespecified criteria of equivalence (OR 0.55, 95% CI 0.34 - 0.88 and 1.03, 95% CI 0.62 - 1.71 respectively). No clinically significant difference was detected in the incidence of posthospitalisation behavioural changes between groups in children under the age of thirteen (absolute difference in effect sizes between inpatient and CBPU care groups: 0.04, 95% CI - 0.33 to 0.25 and between day-case and CBPU care groups: 0.05, 95% CI - 0.26 to 0.35). Parental satisfaction was substantially higher in the CBPU group compared to both inpatient care (effect size 1.3, 95% CI 1.1 - 1.4) and day-case care (effect size 1.2, 95% CI 0.9 - 1.3). The cost minimisation analysis estimated that CBPU care provided a 20% saving to the hospital compared with inpatient care (sensitivity analysis 4% to 43%), whilst day-case care provided a 35% saving compared with inpatient care (sensitivity analysis 20% - 58%). The Willingness-to-pay analysis indicated that a CBPU was likely to be able to sustain a $50 co-payment. Conclusion: CBPU care was demonstrated to offer a standard of clinical care at least equivalent to inpatient and day-case care, whilst being substantially more acceptable to parents. CBPU was no more costly to the hospital than inpatient care although marginally more expensive than day-case care. It is likely therefore that CBPU care does have a role as an alternative to inpatient care for a substantial group of patients in major paediatric tertiary referral centres such as the Royal Children's Hospital. CBPU care may also improve the community's acceptance of day-case care by emphasising that it is both safe and appropriate for parents to look after their own children following many medical procedures.
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ItemThe Introduction of hepatitis B vaccine in rural Vietnam( 2004)Vietnam, a nation of almost 80 million people with a high rate of chronic infection with the hepatitis B virus (HBV), is currently expanding its introduction of hepatitis B vaccine (HepB vaccine) for infants across the nation. This is occurring within an immunisation program widely commended for its high coverage and achievements in disease control. During 1997, HepB vaccine was introduced for a small proportion of infants in urban areas, using a locally manufactured product which had not previously been objectively evaluated in the field. In addition, the problem of HBV infection itself had not been adequately quantitated, making subsequent evaluation of the program difficult. To make HepB vaccine available more widely and at birth, as is needed to prevent the perinatal infection responsible for a large proportion of chronic HBV infection, its storage outside the cold chain has been suggested. This would enable its use for infants born in remote areas lacking access and refrigeration, but scientific verification of the vaccine's immunogenicity and protective efficacy (PE) when used in this way is lacking. In addition, it is not certain that birth dosing, nor indeed the three required doses of the vaccine itself will be acceptable to Vietnamese mothers, who are unused to infants receiving any vaccines before the age of two months and not unreasonably concerned about injection safety. In this thesis I examine the situation with respect to the conduct of the Expanded Program on Immunisation (EPI) in one rural province of central northern Vietnam, and community attitudes towards this program and the introduction of HepB vaccine. Grave concerns about the planning, safety, effectiveness and veracity of reporting of the Program are raised, and health worker and community education programs recommended prior to the introduction of birth dosing with HepB vaccine. I report on a survey of the seroprevalence of HBV infection in this location, confirming very high rates of perinatal infection and a monotonous increase in exposure with age. I also compare the immunogenicity of the locally produced vaccine in two different formulations with that of two internationally licensed Korean vaccines, concluding that the dose currently used in the Vietnamese EPI should be increased. I evaluate three different strategies for the introduction of HepB vaccine in varying geographic and demographic milieu, both scientifically in terms of their immunogenicity and PE, and for their operational feasibility and likely generalisability throughout Vietnam. I provide further evidence in support of the immunogenicity of HepB vaccine stored at ambient temperature, but only limited evidence relating to PE, probably because of the low dose of vaccine available. I compare the responses of local communities to differing levels of dissemination of information relevant to the introduction of HepB vaccine, and of health workers to training to improve their conduct of the EPI. Improving the EPI, including introduction of HepB vaccine with a birth dose, seems both feasible and acceptable to all concerned. Finally, I evaluate the activities conducted by examining changes in the prevalence of two objectively measurable indicators of the conduct of the EPI. Whilst rates of scars following bacille Calmette-Guerin vaccine increased substantially, rates of immunity to measles amongst older infants did not.