Paediatrics (RCH) - Research Publications
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ItemNo long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine(Elsevier, 2016-06)Background: A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. Objective: This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Methods: Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Results: Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Conclusion: Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group.
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ItemThe Effect of Intermittent Antenatal Iron Supplementation on Infant Outcomes in Rural Vietnam: A Cluster Randomized Trial(SCIENCEDOMAIN International, 2015)Objectives: Intermittent antenatal iron supplementation is an attractive alternative to daily dosing during pregnancy, however the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Vietnam. Methods: This cluster randomised trial was conducted in Ha Nam province, Vietnam. 1,258 pregnant women in 104 communes were assigned to daily iron-folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Results: There was no difference in birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 g; 95% CI -22 to 78), or twice weekly MMN compared to daily IFA (MD -36.8 g; 95% CI -82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly compared to daily IFA (geometric mean ratio (GMR) 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (GMR 0.62; 95% CI 0.57 to 0.68), with no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56). Conclusions: Twice-weekly antenatal IFA supplementation achieved similar mean birthweight, and improved cognitive scores in infants at 6 months of age, compared to daily IFA supplementation, and should be considered for use in settings with low anemia prevalence.
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ItemAtrioventricular block after ASD closure(BMJ PUBLISHING GROUP, 2016)OBJECTIVE: Secundum atrial septal defect (ASD) is a common congenital heart defect. There is limited data on both early and late atrioventricular (AV) block post ASD closure. The aim of this study was to determine the incidence and risk factors of AV block associated with ASD closure. METHODS: A retrospective analysis of all patients who underwent ASD closure either with a device or surgical method at the Royal Children's Hospital Melbourne between 1996 and 2010 was performed. Baseline demographics, procedural details and follow-up data were collected from medical records. RESULTS: A total of 378 patients were identified; 242 in the device group and 136 in the surgical group. Fourteen patients (3.7%) had AV block (1 with second degree and 13 with first degree) at a median follow-up of 28 months; 11/242 (4.5%) in the device group and 3/135 (2.2%) in the surgical group (p=0.39). Six patients had new-onset AV block after ASD closure. In the device subgroup, patients with AV block at follow-up had a larger indexed device size compared with those without (22 (15-31) vs 18(7-38), p=0.02). Multivariate analysis revealed the presence of AV block either pre procedure or post procedure to be the only variables associated with late AV block. CONCLUSIONS: Late AV block in patients with repaired ASD is rare and most likely independent of the technique used. In the device subgroup, the only risk factor identified to be associated with late AV block was the presence of either preprocedural or postprocedural AV block, so long-term follow-up for these patients should be provided.
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ItemHigh-level mobility skills in children and adolescents with traumatic brain injury(TAYLOR & FRANCIS INC, 2015-12-06)AIM: To evaluate the reliability, validity and responsiveness of the High-level Mobility Assessment Tool (HiMAT) in children and adolescents with traumatic brain injury (TBI) and to compare the mobility skills of children with TBI to those of healthy peers. METHOD: The mobility skills of 52 children with moderate and severe TBI (36 males; mean age = 12 years, range = 6-17) were assessed using the HiMAT and the Pediatric Evaluation of Disability Inventory (PEDI). Inter-rater reliability, re-test reliability and responsiveness of the HiMAT were evaluated in sub-groups by comparing results scored at several time-points. The HiMAT scores of children with TBI were compared with those of a healthy comparative cohort. RESULTS: The HiMAT demonstrated excellent inter-rater reliability (ICC = 0.93), re-test reliability (ICC = 0.98) and responsiveness to change (p = 0.002). The PEDI demonstrated a ceiling effect in mobility assessment of ambulant children with TBI. The HiMAT scores of children with TBI were lower than those of their healthy peers (p < 0.001). INTERPRETATION: The HiMAT is a reliable, valid and sensitive measure of high-level mobility skills following childhood TBI. The high-level mobility skills of children with TBI are less proficient than their peers.
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ItemNew Australian sauropods shed light on Cretaceous dinosaur palaeobiogeography.(Springer Science and Business Media LLC, 2016-10-20)Australian dinosaurs have played a rare but controversial role in the debate surrounding the effect of Gondwanan break-up on Cretaceous dinosaur distribution. Major spatiotemporal gaps in the Gondwanan Cretaceous fossil record, coupled with taxon incompleteness, have hindered research on this effect, especially in Australia. Here we report on two new sauropod specimens from the early Late Cretaceous of Queensland, Australia, that have important implications for Cretaceous dinosaur palaeobiogeography. Savannasaurus elliottorum gen. et sp. nov. comprises one of the most complete Cretaceous sauropod skeletons ever found in Australia, whereas a new specimen of Diamantinasaurus matildae includes the first ever cranial remains of an Australian sauropod. The results of a new phylogenetic analysis, in which both Savannasaurus and Diamantinasaurus are recovered within Titanosauria, were used as the basis for a quantitative palaeobiogeographical analysis of macronarian sauropods. Titanosaurs achieved a worldwide distribution by at least 125 million years ago, suggesting that mid-Cretaceous Australian sauropods represent remnants of clades which were widespread during the Early Cretaceous. These lineages would have entered Australasia via dispersal from South America, presumably across Antarctica. High latitude sauropod dispersal might have been facilitated by Albian-Turonian warming that lifted a palaeoclimatic dispersal barrier between Antarctica and South America.
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ItemThe dentary of Australovenator wintonensis (Theropoda, Megaraptoridae); implications for megaraptorid dentition.(PeerJ, 2015)Megaraptorid theropods were an enigmatic group of medium-sized predatory dinosaurs, infamous for the hypertrophied claw on the first manual digit. Megaraptorid dentition is largely restricted to isolated teeth found in association with skeletal parts; however, the in situ maxillary dentition of Megaraptor was recently described. A newly discovered right dentary pertaining to the Australovenator holotype preserves in situ dentition, permitting unambiguous characterisation of the dentary tooth morphology. The new jaw is virtually complete, with an overall elongate, shallow profile, and fifteen visible in situ teeth at varying stages of eruption. In situ teeth confirm Australovenator exhibited modest pseudoheterodonty, recurved lateral teeth with a serrate distal carina and reduced mesial carina, similar to other megaraptorids. Australovenator also combines of figure-of-eight basal cross-section with a lanceolate shape due to the presence of labial and lingual depressions and the lingual twist of the distal carina. Computed tomography and three-dimensional imagery provided superior characterisation of the dentary morphology and enabled an accurate reconstruction to a pre-fossilised state. The newly established dental morphology also afforded re-evaluation of isolated theropod teeth discovered at the Australovenator holotype locality and from several additional Winton Formation localities. The isolated Winton teeth are qualitatively and quantitatively similar to the in situ dentary teeth of Australovenator, but are also morphometrically similar to Abelisauridae, Allosauridae, Coelophysoidea, Megalosauridae and basal Tyrannosauroidea. Qualitative characters, however, clearly distinguish the teeth of Australovenator and the isolated Winton teeth from all other theropods. Evidence from teeth suggests megaraptorids were the dominant predators in the Winton Formation, which contrasts with other penecontemporaneous Gondwanan ecosystems.
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ItemThe pes of Australovenator wintonensis (Theropoda: Megaraptoridae): analysis of the pedal range of motion and biological restoration.(PeerJ, 2016)The pedal range of motion in Australovenator wintonensis is investigated to determine what influence soft tissue had on range of motion in the foot. Fortunately, the theropod pes shares a close morphology with extant large cursorial birds. Therefore, to better understand the pedal range of motion of Australovenator, the pedal range of motion of Dromaius novaehollandiae (commonly known as the emu) was analysed with and without soft tissue. We used a variety of innovative digital techniques to analyse the range of motion and biologically restore the Australovenator pes. Computed tomography scans of Dromaius pes in fully flexed and fully extended positions provided the soft tissue range of motion limits. The bone on bone range of motion of the same specimen was replicated following the removal of soft tissue. It was identified that there was an increase in range of motion potential with the removal of soft tissue. This variation provided a guide to develop the potential range of motion of a fully fleshed Australovenator pes. Additionally, the dissection of the Dromaius pes provided a guide enabling the replication of the corresponding soft tissue and keratin sheaths of the Australovenator pes.
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ItemForearm Range of Motion in Australovenator wintonensis (Theropoda, Megaraptoridae).(Public Library of Science (PLoS), 2015)The hypertrophied manual claws and modified manus of megaraptoran theropods represent an unusual morphological adaptation among carnivorous dinosaurs. The skeleton of Australovenator wintonensis from the Cenomanian of Australia is among the most complete of any megaraptorid. It presents the opportunity to examine the range of motion of its forearm and the function of its highly modified manus. This provides the basis for behavioural inferences, and comparison with other Gondwanan theropod groups. Digital models created from computed tomography scans of the holotype reveal a humerus range of motion that is much greater than Allosaurus, Acrocanthosaurus, Tyrannosaurus but similar to that of the dromaeosaurid Bambiraptor. During flexion, the radius was forced distally by the radial condyle of the humerus. This movement is here suggested as a mechanism that forced a medial movement of the wrist. The antebrachium possessed a range of motion that was close to dromaeosaurids; however, the unguals were capable of hyper-extension, in particular manual phalanx I-2, which is a primitive range of motion characteristic seen in allosaurids and Dilophosaurus. During flexion, digits I and II slightly converge and diverge when extended which is accentuated by hyperextension of the digits in particular the unguals. We envision that prey was dispatched by its hands and feet with manual phalanx I-2 playing a dominant role. The range of motion analysis neither confirms nor refutes current phylogenetic hypotheses with regards to the placement of Megaraptoridae; however, we note Australovenator possessed, not only a similar forearm range of motion to some maniraptorans and basal coelurosaurs, but also similarities with Tetanurans (Allosauroids and Dilophosaurus).
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ItemFrench Intensive Care Society, International congress - Réanimation 2016.(Springer Science and Business Media LLC, 2016-06)
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ItemDeterminants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries(BMJ PUBLISHING GROUP, 2016-11)BACKGROUND: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally. METHODS: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression. RESULTS: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed. CONCLUSIONS: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas. TRIAL REGISTRATION NUMBER: NCT02179112; Pre-results.