Paediatrics (RCH) - Research Publications
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ItemHisto-blood Group Antigen status of Australian Aboriginal children and seropositivity following oral rotavirus vaccination( 2022)Background: High rates of breakthrough rotavirus gastroenteritis have been reported among Aboriginal children living in rural and remote Australia despite receipt of two doses of oral rotavirus vaccine. Histo-blood group antigens (HBGAs) may mediate rotavirus genotype-dependent differences in susceptibility to rotavirus infection and immune responses to rotavirus vaccination. Methods: HBGA phenotype – Lewis and secretor status - was determined by enzyme immunoassay of saliva samples obtained from Australian Aboriginal children who were enrolled at age 6 to <12 months in a randomised clinical trial of an additional (booster) dose of oral rotavirus vaccine. Participants had received the routine two-dose schedule of oral rotavirus vaccine administered at age 6 weeks and 4 months. Non-secretor phenotype was confirmed by DNA extraction to identify FUT2 ‘G428A’ mutation. Rotavirus seropositivity was defined as serum anti-rotavirus IgA ≥ 20 AU/mL measured by ELISA on enrolment. Results: Of 156 children, 119 (76%) were secretors, 129 (83%) were Lewis antigen positive, and 105 (67%) were rotavirus IgA seropositive. Eighty-seven of 119 (73%) secretors were rotavirus seropositive, versus 4/9 (44%) weak secretors and 13/27 (48%) non-secretors. Eighty-nine of 129 (69%) Lewis antigen positive children were rotavirus seropositive versus 10 of 19 (53%) of those who were Lewis antigen negative. Conclusions Most Australian Aboriginal children were secretor and Lewis antigen positive. Non-secretor children were less likely to be seropositive for rotavirus following vaccination, but this phenotype was less common. HBGA status is unlikely to fully explain the underperformance of rotavirus vaccine at a population level among Australian Aboriginal children.
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ItemA child presents with acute kidney injury, alkalosis and hypercalcaemia-a new-age cause for a historical syndrome: Answers(Springer, 2022-08)On further history, it was discovered that the family had been using alkaline water as an alternate source of oral fluids given its reported health benefits. Alkaline water is advertised as negatively charged water with a pH of 8–10. These properties are marketed to provide significant health benefits including increased energy levels, reduced effects of ageing and stress and reduced incidence of illness and disease. Alkaline water contains calcium and magnesium carbonate, both exogenous sources of absorbable alkaline. The consumption of alkaline water in this case resulted in a milk-alkali syndrome with hypercalcaemia, metabolic alkalosis and an acute on chronic kidney injury. It was not detected for several months, and as a result, had a significant negative impact on this patient and his family. He required frequent venepuncture, increased clinical reviews (further complicated by the current COVID-19 pandemic) and regular titration of medications. Fortunately, on cessation of the alkaline water, his creatinine returned to baseline and calcium and acid–base normalised.
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ItemInterhospital transport of children with bronchiolitis by a statewide emergency transport service(AUSTRALASIAN MED PUBL CO LTD, 2021-09)Objective: To investigate the rate of interhospital emergency transport for bronchiolitis and intensive care admission following the introduction of high flow nasal cannula and standardised paediatric observation and response charts. Design: Retrospective cohort study. Setting: A statewide paediatric intensive care transport service and its two referral paediatric intensive care units (PICUs) in Victoria, Australia. Participants: Children less than 2 years old emergently transported with bronchiolitis during two time periods: 2008-2012 and 2015-2019. Main outcome measures: Incidence rates of bronchiolitis transport episodes, PICU admissions and respiratory support. Results: 802 children with bronchiolitis were transported during the study period, 233 in the first period (2008-2012) and 569 in the second period (2015-2019). The rate of interhospital transport for bronchiolitis increased from 32.9 to 71.8 per 100 000 children aged 0-2 years. The population-adjusted rate of PICU admission increased from 16.2 to 36.6 per 100 000 children aged 0-2 years. Metropolitan hospitals were the predominant referral source and this increased from 60.1% of transports to 78.6% (P < 0.001). In children admitted to a PICU, the administration of high flow nasal cannula during transport increased significantly from 1.7% to 75.9% (P < 0.001) and a concomitant reduction in continuous positive airway pressure and mechanical ventilation occurred (40-12.4% and 27-6.9% respectively; P < 0.001). The proportion of mechanical ventilation as well as PICU and hospital length of stay decreased over time. Conclusions: The population-adjusted rate of interhospital transport and admission to the PICU for bronchiolitis increased over time. This occurred despite a lower rate of non-invasive and invasive mechanical ventilation during transport and in the PICU.
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ItemCharacteristics and outcomes of children receiving intensive care therapy within 12 hours following a medical emergency team event(AUSTRALASIAN MED PUBL CO LTD, 2021-09)Objectives: To describe characteristics and outcomes of children requiring intensive care therapy (ICT) within 12 hours following a medical emergency team (MET) event. Design: Retrospective cohort study. Setting: Quaternary paediatric hospital. Patients: Children experiencing a MET event. Measurements and main results: Between July 2017 and March 2019, 890 MET events occurred in 566 patients over 631 admissions. Admission to intensive care followed 183/890 (21%) MET events. 76/183 (42%) patients required ICT, defined as positive pressure ventilation or vasoactive support in intensive care, within 12 hours. Older children had a lower risk of requiring ICT than infants aged < 1 year (age 1-5 years [risk difference, -6.4%; 95% CI, -11% to -1.6%; P = 0.01] v age > 5 years [risk difference, -8.0%; 95% CI, -12% to -3.8%; P < 0.001]), while experiencing a critical event increased this risk (risk difference, 16%; 95% CI, 3.3-29%; P = 0.01). The duration of respiratory support and intensive care length of stay was approximately double in patients requiring ICT (ratio of geometric means, 2.0 [95% CI, 1.4-3.0] v 2.1 [95% CI, 1.5-2.8]; P < 0.001) and the intensive care mortality increased (risk difference, 9.6%; 95% CI, 2.4-17%; P = 0.01). Heart rate, oxygen saturation and respiratory rate were the most commonly measured vital signs in the 6 hours before the MET event. Conclusions: Approximately one-fifth of MET events resulted in intensive care admission and nearly half of these required ICT within 12 hours. This group had greater duration of respiratory support, intensive care and hospital length of stay, and higher mortality. Age < 1 year and a critical event increased the risk of ICT.
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ItemStatistical analysis plan for the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial(ELSEVIER, 2021-03)Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses.
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ItemNo Preview AvailableTime to act on climate change(WILEY, 2022-12-05)
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ItemNo Preview AvailableAssociations between dual‐decline in cognition and gait speed with risk of dementia – results from the ASPREE trial cohort(Wiley, 2022-12)Background Dual decline in gait speed and cognition is associated with an increased risk of dementia. However, it is unclear if risks are conferred by decline in domain‐specific cognition and gait. We aimed to examine associations between dual decline in gait speed and cognition (global cognition, memory, processing speed and verbal fluency) with risk of dementia. Methods Prospective cohort study. Participants were from the ASPREE (ASPirin in Reducing Events in the Elderly) study, a double‐blind, randomized, placebo‐controlled trial of low dose aspirin in older adults (≥70 years; ≥65 if US minority). Of 19,114 randomized participants, 16,855 (88%) had longitudinal gait and cognitive data. Gait speed was measured at 0, 2, 4, 6 years and close‐out. Cognitive measures included Modified Mini‐Mental State examination (3MS, global cognition), Hopkins Verbal Learning Test‐Revised (HVLT‐R, memory), Symbol Digit Modalities (SDMT, processing speed) and Controlled Oral Word Association Test (COWAT‐F, verbal fluency), assessed at years 0, 1, 3, 5, and close‐out. Participants were classified into four groups: 1) dual decline in gait and cognition; 2) gait decline only; 3) cognitive decline only and 4) non‐decliners. Cognitive decline was defined as membership of the lowest tertile of annual change. Gait decline was defined as decline in gait speed ≥0.05 m/s per year across the study. Dementia (DSM‐IV criteria) was adjudicated by an expert panel using cognitive tests, functional status and clinical records. Cox proportional hazard models were used to estimate risk of dementia adjusting for covariates with death as competing risk. Results The mean age of participants was 75.0 (SD4.4) years. Compared with non‐decliners, risk of dementia was highest in the gait+HVLT‐R decliners (HR 24.7; 95% CI 16.3‐37.3), followed by the gait+3MS (HR 22.2; 95% CI 15.0‐32.9), gait+COWAT‐F (HR 4.66 95%; CI 3.5‐6.3) and gait+SDMT (HR 4.3 95% CI 3.2‐5.8) groups. Dual decliners also had higher risk of dementia than those with either gait or cognitive decline alone for 3MS and HVLT‐R. Conclusion The combination of decline in gait speed and memory may be the best suited to predict future dementia risk.
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ItemStability of combined Le Fort I maxillary advancement and mandibular reduction.(Walter de Gruyter GmbH, 2003-11)BACKGROUND: There have been reports that correction of severe Class III abnormality by single jaw surgery may invite relapse in the long-term. The purpose of this study was to retrospectively evaluate the stability of combined Le Fort I maxillary advancement and bilateral sagittal split osteotomies for mandibular reduction. METHODS: Thirty patients with a skeletal Class III malocclusion underwent bimaxillary surgery using rigid fixation and interpositional bone grafting of the maxilla. The average age was 24.4 years, and the mean follow-up period was 20 months (Range: 12-63 months). Post-operative changes were measured on lateral cephalometric radiographs using an anatomical best-fit technique. RESULTS: The maxilla was advanced, on average, 6.1 mm (SD: 1.8 mm) and repositioned superiorly at PNS 1.9 mm (SD: 2.1 mm). The mandible was repositioned posteriorly 5.6 mm ISD: 4.2 mm) at menton, which also auto-rotated superiorly. At follow-up, the maxilla relapsed horizontally 0.6 mm (SD: 1.1 mm, p < 0.01) with no significant vertical change. The maxillary central incisors were proclined and the interincisal angle was reduced. Menton relapsed anteriorly 1.4 mm (SD: 2.7 mm, p < 0.01), and gonion rotated superiorly 1.5 mm (SD: 2.3 mm, p < 0.001). In 67 per cent of cases menton moved anteriorly less than 2.5 mm. The overjet and overbite did not change significantly. CONCLUSIONS: The data show that 12-months post-operatively, maxillary advancement combined with mandibular setback was relatively stable in the horizontal and vertical planes.
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ItemThe parenting skill development and education service: Telehealth support for families at risk of child maltreatment during the COVID-19 pandemic(WILEY, 2022-08)Children are at heightened risk of maltreatment during community wide crises. The Parenting Skill Development and Education (PSDE) Service is a 6‐week telehealth intervention designed and implemented during the COVID‐19 pandemic to support families with young children in Australia at risk of child maltreatment. This study aimed to conduct a formative review of the PSDE service to (a) describe families accessing the PSDE during the pandemic, (b) determine parent and referrers' satisfaction of the service and (c) explore clinicians' experiences of service delivery. A mixed‐method study design incorporating the analysis of routinely collected data, and qualitative interviews with clinicians was conducted. Participants were 11 families displaying child maltreatment risk and 11 clinicians. Parents accessing the service were experiencing considerable risk factors for child maltreatment. The service was deemed acceptable by parents and referrers; however, several challenges in telehealth delivery were documented including parent engagement, technology difficulties and assessing child safety. Our findings highlighted the importance of ensuring adequate support and monitoring of families where there is child maltreatment risk during the COVID‐19 pandemic. In addition, these findings highlight the acceptability of telehealth services to support families at risk of child maltreatment for families, clinicians, and referrers.
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ItemNo Preview AvailableNormal skeletal development of mice lacking matrilin 1:: Redundant function of matrilins in cartilage?(AMER SOC MICROBIOLOGY, 1999-11)Matrilin 1, or cartilage matrix protein, is a member of a novel family of extracellular matrix proteins. To date, four members of the family have been identified, but their biological role is unknown. Matrilin 1 and matrilin 3 are expressed in cartilage, while matrilin 2 and matrilin 4 are present in many tissues. Here we describe the generation and analysis of mice carrying a null mutation in the Crtm gene encoding matrilin 1. Anatomical and histological studies demonstrated normal development of homozygous mutant mice. Northern blot and biochemical analyses show no compensatory up-regulation of matrilin 2 or 3 in the cartilage of knockout mice. Although matrilin 1 interacts with the collagen II and aggrecan networks of cartilage, suggesting that it may play a role in cartilage tissue organization, studies of collagen extractability indicated that collagen fibril maturation and covalent cross-linking were unaffected by the absence of matrilin 1. Ultrastructural analysis did not reveal any abnormalities of matrix organization. These data suggest that matrilin 1 is not critically required for cartilage structure and function and that matrilin 1 and matrilin 3 may have functionally redundant roles.