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Royce S.G.,Murdoch Childrens Research Institute | Sedjahtera A.,Murdoch Childrens Research Institute | Samuel C.S.,Howard Florey Institute | Samuel C.S.,University of Melbourne | And 4 more authors.
Clinical Science | Year: 2013

Although CSs (corticosteroids) demonstrate potent effects in the control of airway inflammation in asthma, many patients continue to experience symptoms and AHR (airway hyper-responsiveness) despite optimal treatment with these agents, probably due to progressive airway remodelling. Identifying novel therapies that can target airway remodelling and/or airway reactivity may improve symptom control in these patients. We have demonstrated previously that the anti-fibrotic hormone RLN (relaxin) can reverse airway remodelling (epithelial thickening and subepithelial fibrosis) and AHR in a murine model of AAD (allergic airways disease). In the present study, we compared the effects of RLN with a CS (methylprednisolone) on airway remodelling and AHR when administered independently or in combination in the mouse AAD model. Female mice at 6-8 weeks of age were sensitized and challenged to OVA (ovalbumin) over a 9-week period and treated with methylprednisolone, RLN, a combination of both treatments or vehicle controls. Methylprednisolone was administered intraperitoneally on the same day as nebulization for 6 weeks, whereas recombinant human RLN-2 was administered via subcutaneously implanted osmotic mini-pumps from weeks 9-11. RLN or methylprednisolone alone were both able to significantly decrease subepithelial thickness and total lung collagen deposition; whereas RLN but not methylprednisolone significantly decreased epithelial thickness and AHR. Additionally, combination therapy with CS and RLN more effectively reduced subepithelial collagen thickness than either therapy alone. These findings demonstrate that RLN can modulate a broader range of airway remodelling changes and AHR than methylprednisolone and the combination of both treatments offers enhanced control of subepithelial fibrosis. © The Authors Journal compilation © 2013 Biochemical Society.


Giallo R.,Murdoch Childrens Research Institute | Giallo R.,RMIT University | Woolhouse H.,Murdoch Childrens Research Institute | Gartland D.,Murdoch Childrens Research Institute | And 5 more authors.
European Child and Adolescent Psychiatry | Year: 2015

Children exposed to maternal depression during pregnancy and in the postnatal period are at increased risk of a range of health, wellbeing and development problems. However, few studies have examined the course of maternal depressive symptoms in the perinatal period and beyond on children’s wellbeing. The present study aimed to explore the relationship between both the severity and chronicity of maternal depressive symptoms across the early childhood period and children’s emotional–behavioural difficulties at 4 years of age. Data from over 1,085 mothers and children participating in a large Australian prospective pregnancy cohort were used. Latent class analysis identified three distinct trajectories of maternal depressive symptoms from pregnancy to 4 years postpartum: (1) no or few symptoms (61 %), (2) persistent subclinical symptoms (30 %), and (3) increasing and persistently high symptoms (9 %). Regression analyses revealed that children of mothers experiencing subclinical and increasing and persistently high symptoms were at least two times more likely to have emotional–behavioural difficulties than children of mothers reporting minimal symptoms, even after accounting for known risk factors for poor outcomes for children. These findings challenge policy makers and health professionals to consider how they can tailor care and support to mothers experiencing a broader spectrum of depressive symptoms across the early childhood period, to maximize opportunities to improve both short-and long-term maternal and child health outcomes. © 2015, Springer-Verlag Berlin Heidelberg.


Randall M.,The Royal Childrens Hospital | Imms C.,La Trobe University | Carey L.,National Stroke Research Institute
Developmental Medicine and Child Neurology | Year: 2012

Aim This paper reports the second phase of a study to extend the Melbourne Assessment for use with children with neurological impairment aged 2 to 4years. The aim was to establish if (1) children's scores on the Modified Melbourne Assessment (MMA) and the Quality of Upper Extremity Skills Test (QUEST) showed a moderate to high, positive relation, (2) children had comparable behaviours for task and time demands on both tools, and (3) scores on the MMA could discriminate between children with mild, moderate, and severe levels of upper limb impairment. Method An observational study of 30 children (19 males, 11 females) with neurological impairment aged 2 to 4years. Twenty-four children had spasticity (20 with a unilateral and four with a bilateral impairment) and two children presented with athetosis, two with ataxia, and two with hypotonia. Results A high, positive relation was found between children's scores on the MMA and the QUEST (ρ=0.90; p=0.001). The clinical use of the MMA was comparable to the QUEST. MMA scores were able to discriminate between children's levels of upper limb impairment as determined by clinicians' ratings (F 2,27=67.76, p=0.001). Interpretation These findings suggest the MMA can be clinically useful for children as young as 2.5years and has the advantage of being valid for use with older children. Scores from the tool can also provide therapists with a quantitative means of consistently reporting level of upper limb impairment. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.


Adair B.,University of Melbourne | Said C.M.,University of Melbourne | Rodda J.,The Royal Childrens Hospital | Morris M.E.,University of Melbourne
Developmental Medicine and Child Neurology | Year: 2012

Aim To evaluate studies on the psychometric properties of measurement tools used to quantify functional mobility in children with hereditary spastic paraplegia (HSP) and other childhood neurological conditions. Method Two independent reviewers identified measures previously used by clinicians to quantify functional mobility. Because our primary interest was HSP, the first search identified measurement tools in studies that included those with HSP. To enhance the generalizability, the second search examined the reliability, validity, and responsiveness of tools in children with a range of neurological conditions such as cerebral palsy, spinal muscular atrophy, Down syndrome, and traumatic brain injury. The Consensus-based Standards for the Selection of Health Measurement Instruments was used to rate the methodological quality of identified articles. Results The Gillette Functional Assessment Questionnaire (FAQ), the Functional Mobility Scale (FMS), the Gross Motor Function Measure (GMFM), the Rivermead Motor Assessment, and the Walking Index for Spinal Cord Injury II were identified for quantifying functional mobility. The FMS and GMFM were reliable, valid, and responsive to changes across a range of childhood neurological conditions. The FAQ was reliable and valid for measuring functional mobility in similar populations. Interpretation The FAQ, FMS, and GMFM are valid, reliable, and responsive measures in children with a range of neurological conditions. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.


Efron D.,Murdoch Childrens Research Institute | Efron D.,University of Melbourne | Efron D.,The Royal Childrens Hospital | Lycett K.,Murdoch Childrens Research Institute | And 3 more authors.
Sleep Medicine | Year: 2014

Objective: Sleep problems are common in children with attention-deficit/hyperactivity disorder (ADHD), yet little is known about sleep medication use in this population. The aim of this study was to describe sleep medication use, as well as associated child and family characteristics in school-aged children with ADHD. Method: Sleep medication use was ascertained using a prospective parent-completed seven-night sleep and medication log. Exposure variables included socio-demographic characteristics, total sleep problem severity (Children's Sleep Habits Questionnaire), ADHD severity and subtype (ADHD Rating Scale IV), ADHD medication use, internalising and externalising co-morbidities (Anxiety Disorders Interview Schedule for Children/Parent version IV) and parent mental health (Depression Anxiety Stress Scale). Results: Two hundred and fifty-seven children with ADHD participated and of these 57 (22%) were taking sleep medication (melatonin 14% and clonidine 9%). Sleep medication use was associated with combined-type ADHD and ADHD medication use. The presence of co-occurring internalising and externalising co-morbidities was also associated with sleep medication use in ad hoc analyses. Conclusion: Sleep medication use is common in children with ADHD and is associated with combined-type ADHD and use of ADHD medication. Further research is needed on the broad functional benefits and long-term safety of sleep medication in this population. © 2014 Elsevier B.V.


Huo C.W.,The Royal Childrens Hospital
Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand | Year: 2012

Radial head dislocation secondary to obstetric brachial plexus palsy is a rare complication that may occur a few years after birth. Five cases were examined and a comprehensive literature search was performed. Although it is a concern for parents, the dislocation resulted in mild or minimal functional impairment for all five children. Surgical interventions such as biceps tendon transfer, radial head open reduction or excision and annular ligament reconstruction were largely ineffective in significantly improving ranges of motion. Clinicians should be aware of the potentially futile outcomes and risks associated with the surgical treatment of radial head dislocation.


Shore B.J.,Childrens Hospital Boston | White N.,The Royal Childrens Hospital | Graham H.K.,The Royal Childrens Hospital
Journal of Children's Orthopaedics | Year: 2010

Purpose: Equinus is the most common deformity in cerebral palsy. However, despite the large volume of published studies, there are poor levels of evidence to support surgical intervention. This study was undertaken to examine the current evidence base for the surgical management of equinus deformity in cerebral palsy. Methods: A systematic review of the literature using "equinus deformity", "cerebral palsy" and "orthopaedic surgery" generated 49 articles. After applying inclusion and exclusion criteria, 35 articles remained. The Oxford Centre for Evidence-Based Medicine (CEBM) levels of evidence and the Methodological Index for Non-Randomized Studies (MINORS) were used to grade the articles. Results: Studies ranged in sample size from 9 to 156 subjects, with an average of 38 subjects. The mean age of subjects at index surgery ranged from 5 to 19 years. Nineteen studies used instrumented gait analysis, with an average follow-up of 2.8 years. Seven studies reported that a younger age at index surgery was associated with an increased risk of recurrent equinus. The average rate of calcaneus in hemiplegic children was 1% and it was 15% in those with spastic diplegia. Most studies were level 4 quality of evidence, leading to, at best, only grade C recommendation. Conclusions: Cerebral palsy subtype (hemiplegia versus diplegia) and age at index surgery were the two most important variables for determining the outcome of surgery for equinus deformity in cerebral palsy. Despite the great emphasis on differences in surgical procedures, there was less evidence to support the type of operation in relation to outcome. © 2010 EPOS.


Rodwell K.,The Royal Childrens Hospital | Edwards P.,The Royal Childrens Hospital | Ware R.S.,University of Queensland | Boyd R.,University of Queensland
Developmental Medicine and Child Neurology | Year: 2012

Aim The aim of this paper was to systematically review the efficacy and safety of botulinum toxin (BoNT) injections to the salivary glands to treat drooling in children with cerebral palsy and neurodevelopmental disability. Method A systematic search of The Cochrane Central Register of Controlled Trials, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and the Physiotherapy Evidence Database (PEDro) was conducted (up to 1 October 2011). Data sources included published randomized controlled trials (RCTs) and prospective studies. Results Sixteen studies met inclusion criteria. Three outcome measures support the effectiveness of BoNT for drooling. One RCT found an almost 30% reduction in the impact of drooling on patients' lives, as measured by the Drooling Impact Scale (mean difference -27.45; 95% confidence interval [CI] -35.28 to -19.62). There were sufficient data to pool results on one outcome measure, the Drooling Frequency and Severity Scale, which supports this result (mean difference -2.71; 95% CI -4.82 to -0.60; p<0.001). There was a significant reduction in the observed number of bibs required per day. The incidence of adverse events ranged from 2 to 41%, but was inconsistently reported. One trial was terminated early because of adverse events. Interpretation BoNT is an effective, temporary treatment for sialorrhoea in children with cerebral palsy. Benefits need to be weighed against the potential for serious adverse events. More studies are needed to address the safety of BoNT and to compare BoNT with other treatment options for drooling. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.


Chan C.-W.,The Royal Childrens Hospital | Chalkiadis G.A.,The Royal Childrens Hospital
Pain Medicine (United States) | Year: 2010

Background: Chronic pain following trauma may be mediated in part by the sympathetic nervous system. There is evidence of sympathetic nervous system dysfunction in patients who suffer from posttraumatic headaches. Not all patients will obtain relief from conventional and antineuropathic medications. Furthermore, the development of adverse effects may limit therapeutic dosing or continuation of these medications. Case Report: A pediatric case of posttraumatic headache is described. The patient failed medical therapy, and a single stellate ganglion blockade was performed for possible sympathetic involvement. Following sympathetic blockade, the patient's headaches resolved completely. The analgesia proved to be long lasting as the patient reported no further headaches at monthly follow-up intervals. The patient did not require any further analgesic medication after the single procedure. Conclusion: Posttraumatic headache is difficult to treat. Although there is evidence of sympathetic nervous system dysfunction in some patients, the extent to which this influences pain remains to be determined. While most cases are treated with a combination of nonpharmacological and pharmacological measures, sympathetic blockade via the stellate ganglion may be an alternative for those patients not responding to conventional therapy.


Coman D.,The Royal Childrens Hospital
Fetal Diagnosis and Therapy | Year: 2010

The identification of trisomy mosaicism in the prenatal setting is often shrouded with uncertainty for the genetic counsellor, and more importantly for the parents. The outcomes for these pregnancies may well be normal, but abnormalities and even in utero death are possibilities depending on the chromosomal abnormality and the degree of mosaicism. Advice to parents following the diagnosis of trisomy 16 mosaicism at chorionic villus sampling, with confirmation at subsequent amniocentesis, and in the setting of apparently normal fetal ultrasonography, is necessarily cautious. Malformations are seen in the majority of infants born following a diagnosis of mosaic trisomy 16 at amniocentesis, and intrauterine growth retardation, with postnatal catch-up, is the rule. We report here a case with a normal outcome by age 2.5 years and in fact with above-average language ability, and in whom trisomy mosaicism was confirmed postnatally. Copyright © 2010 S. Karger AG, Basel.

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