Paediatrics (RCH) - Research Publications
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ItemKawasaki disease and cardiovascular risk: a comprehensive review of subclinical vascular changes in the longer term(WILEY, 2016-07)UNLABELLED: Studies of subclinical vascular changes post-Kawasaki disease indicate that, in general, individuals with a history of coronary artery aneurysms have increased carotid intima-media thickness, evidence of endothelial dysfunction, and increased arterial stiffness, possibly indicative of heightened cardiovascular risk. The results are less consistent for low-risk groups. CONCLUSION: Until data are available from larger prospective studies, it is prudent to advise families of individuals with a history of Kawasaki disease to minimise traditional modifiable cardiovascular risk factors.
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ItemThe immunomodulatory effects of measles-mumps-rubella vaccination on persistence of heterologous vaccine responses(WILEY, 2019-07)It is proposed that measles-containing vaccines have immunomodulatory effects which include a reduction in all-cause childhood mortality. The antibody response to heterologous vaccines provides a means to explore these immunomodulatory effects. This is the first study to investigate the influence of measles-mumps-rubella (MMR) vaccine on the persistence of antibodies to a broad range of heterologous infant vaccinations given in the first year of life. In total, 319 children were included in the study. All infants received routine vaccinations at 6 weeks, 4 and 6 months of age. At 12 months of age, 212 children were vaccinated with MMR and Haemophilus influenzae type b-meningococcus C (Hib-MenC) vaccines while the remaining 99 children had not yet received these vaccines. In the MMR/Hib-MenC-vaccinated group, blood was taken 28 ± 14 days after receiving these vaccines. Antibodies against diphtheria, tetanus, pertussis [pertussis toxin (PT), filamentous hemagglutinin, pertactin], poliomyelitis (type 1, 2, 3) and 13 pneumococcal serotypes were measured. Seroprotection rates and geometric mean antibody concentrations were compared between MMR/MenC-Hib-vaccinated and MMR/MenC-Hib-naïve participants. In the final analysis, 311 children were included. Seroprotection rates were lower in MMR/Hib-MenC-vaccinated children against PT and pneumococcal serotype 19A. After adjustment for prespecified factors, MMR/Hib-MenC-vaccinated infants had significantly higher antibody concentrations against tetanus (likely explained by a boosting effect of the carrier protein, a tetanus toxoid), while for the other vaccine antigens there was no difference in antibody concentrations between the two groups. MMR vaccination given at 12 months of age in a developed country does not significantly influence antibody concentrations to heterologous vaccines received in the first year of life.
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ItemPulmonary Mycobacterium abscessus complex in children with cystic fibrosis: A practical management guideline(WILEY, 2019-05)The treatment of Mycobacterium abscessus complex (MABSC) pulmonary infections is an emerging challenge in patients with cystic fibrosis (CF). Multidrug therapy for prolonged durations is required and carries the significant burden of drug-related toxicity, cost and selective pressure for multiresistant bacteria. International guidelines acknowledge that clinical and in vitro data to support treatment regimens are limited, particularly in children. As part of a collaboration between the infectious diseases and respiratory units at our institution, we have developed a modified treatment guideline that aims to balance the aims of MABSC eradication and slowing disease progression with minimising drug toxicity and resistance. The outcomes of this treatment approach will be monitored and reported. In this manuscript, we discuss the available evidence for treatment choices and present our treatment guideline for paediatric patients with CF and MABSC infection.
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ItemReview article: A primer for clinical researchers in the emergency department: Part VII. Considering a research higher degree in emergency medicine: How does it work, where to start, what to consider(WILEY, 2019-02)In this series we address important topics for clinicians who participate in research or are considering research as part of their career path in emergency medicine. While much emergency research is successfully done by clinicians without a research higher degree (RHD), undertaking a master's degree or doctorate allows a research topic to be pursued in greater depth. It also provides a solid basis for a future research career in terms of research quality, advanced skills, academic progression and track record, as well as eligibility for grants and RHD supervision. The decision to undertake a RHD is not an easy one, and requires consideration of the time and cost involved, as well as the impact on a clinician's life plans. However, the expertise provided through a RHD often ultimately complements clinical training and establishes an excellent foundation for future research and career. This article provides an overview of RHDs and what to consider before embarking on one.
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ItemAdverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations(WILEY, 2018-05)AIMS: Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c-amB and liposomal amphotericin (l-amB) in children. METHODS: Children admitted to the Royal Children's Hospital Melbourne and treated with c-amB or l-amB between January 2010 and September 2013 were included. Clinical and laboratory data were retrospectively extracted from medical records to compare amphotericin-related infusion reactions, nephrotoxicity (glomerulotoxicity and tubulopathy) and hepatotoxicity. RESULTS: Seventy-six children received c-amB and 39 received l-amB. Standard drug administration (recommended dose and infusion time) occurred in 74% (56/76) of patients on c-amB and 85% (33/39) on l-amB. In these 89 children, infusion-related reactions were similar for both c-amB and l-amB (23% (13/56) vs. 9% (3/33); P = 0.15); none occurred in children aged <90 days. There was no difference in amphotericin-associated glomerulotoxicity (c-amB 14% (8/56) vs. l-amB 21% (7/33); P = 0.40) or in the median maximum potassium requirements (c-amB 3.1 vs. l-amB 2.3 mmol kg-1 d-1 ; P = 0.29). Hepatotoxicity occurred more frequently with l-amB than c-amB (83% (24/29) vs. 56% (20/36); P = 0.032). CONCLUSIONS: When appropriately administered, l-amB was associated with more hepatotoxicity than c-amB, with no difference in infusion-related reactions or nephrotoxicity. Differences in adverse effects between the preparations is not as marked in children as reported in adults.
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ItemInterrupted BCG vaccination is a major threat to global child health(ELSEVIER SCI LTD, 2016-04)
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ItemNo Preview AvailableInvasive Group A Streptococcal Disease Epidemiology, Pathogenesis and Management(ADIS INT LTD, 2012)Invasive group A streptococcal infections are uncommon, although serious, infections with high case fatality rates. Periodic resurgences in invasive group A streptococcal infections in industrialized countries have been reported from the 1980s onwards, with current estimates of incidence in these countries of approximately 3-4 per 100 000 population. Infants, pregnant women and the elderly are at increased risk of invasive group A streptococcal infection. The group A streptococcus has an array of virulence factors that underpin its invasive capacity and, in approximately 10% of cases, superantigen toxins produced by the bacteria stimulate a large proportion of T cells, leading to streptococcal toxic shock syndrome. Given the rapid clinical progression, effective management of invasive group A streptococcal infections hinges on early recognition of the disease and prompt initiation of supportive care (often intensive care) together with antibacterial therapy. In cases of toxic shock syndrome, it is often difficult to distinguish between streptococcal and staphylococcal infection before cultures become available and so antibacterial choice must include coverage of both of these organisms. In addition, clindamycin is an important adjunctive antibacterial because of its anti-toxin effects and excellent tissue penetration. Early institution of intravenous immunoglobulin therapy should be considered in cases of toxic shock syndrome and severe invasive infection, including necrotizing fasciitis. Early surgical debridement of necrotic tissue is also an important part of management in cases of necrotizing fasciitis.
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ItemNo Preview AvailableA Comparative Analysis of Polyfunctional T Cells and Secreted Cytokines Induced by Bacille Calmette-Guerin Immunisation in Children and Adults(PUBLIC LIBRARY SCIENCE, 2012-07-19)BCG vaccine is one of the most commonly-administered vaccines worldwide. Studies suggest the protective efficacy of BCG against TB is better for children than for adults. One potential explanation is that BCG induces a better protective immune response in children. Twenty six children and adults were immunised with BCG. The proportion of Th1-cytokine-producing mycobacterial-specific T cells, and the concentrations of secreted cytokines, were measured before and 10 weeks after BCG immunisation. A significant increase in the proportion of mycobacterial-specific cytokine-producing T cells was observed in both age groups. After BCG immunisation, children and adults had comparable proportions of mycobacterial-specific polyfunctional CD4 T cells when measured relative to the total number of CD4 T cells. However, relative to the subset of Th-1-cytokine-producing CD4 T cells, the proportion of polyfunctional cells was greater in children. Concentrations of secreted cytokines were comparable in children and adults. These findings suggest that the mycobacterial-specific cell-mediated immune response induced by BCG immunisation in children and adults is similar. The implication of a shift to a more polyfunctional immune response within the Th1-cytokine-producing CD4 T cells in children is uncertain as this aspect of the immune response has not been assessed as a potential correlate of protection against TB.
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ItemNo Preview AvailableWhat the paediatrician needs to know when pandemic influenza arrives in clinical practice(SPRINGER-VERLAG BERLIN, 2008)Avian (H5N1) influenza or “bird ‘flu” has received considerable attention in both the medical literature and the mass media in the last few years. Despite the tabloids’ portrayal of an imminent threat, to date there have been relatively few cases in humans in spite of large numbers of infected poultry (Hien et al. 2004). However, this may be falsely reassuring. Most indications suggest that it is just a matter of time until the next influenza pandemic occurs (Osterholm 2005). In the words of the UK Chief Medical Officer: “most experts believe that it is not a question of whether there will be another severe influenza pandemic but when” (Department of Health 2005). Although experts are agreed that a future influenza pandemic is almost inevitable, its timing is unpredictable and it is uncertain whether the virus responsible will be H5N1 or another, novel, influenza strain (Osterholm 2005). A recent editorial described avian influenza as a “predicament of extraordinary proportions” (Anonymous 2006). The next influenza pandemic will have a dramatic impact on all levels of health care including the everyday work of doctors. This chapter focuses on the clinical aspects of pandemic influenza about which paediatricians need to be familiar.