Paediatrics (RCH) - Research Publications
Now showing items 1-12 of 1852
Simulation -Based Education for Staff Managing Aggression and Externalizing Behaviors in Children With Autism Spectrum Disorder in the Hospital Setting: Pilot and Feasibility Study Protocol for a Cluster Randomized Controlled Trial
(JMIR PUBLICATIONS, INC, 2020-06-01)
Background: Children with autism spectrum disorder (ASD) frequently demonstrate aggression and externalizing behaviors in the acute care hospital environment. Pediatric acute care nursing staff are often not trained in managing aggression and, in particular, lack confidence in preventing and managing externalizing behaviors in children with ASD. High-fidelity simulation exercises will be used in this study to provide deliberate practice for acute care pediatric nursing staff in the management of aggressive and externalizing behaviors. Objective: The purpose of this study is to conduct a pilot and feasibility cluster randomized controlled trial (RCT) to evaluate the effectiveness of simulation-based education for staff in managing aggression and externalizing behaviors of children with ASD in the hospital setting. Methods: This study has a mixed design, with between-group and within-participant comparisons to explore the acceptability and feasibility of delivering a large-scale cluster RCT. The trial process, including recruitment, completion rates, contamination, and completion of outcome measures, will be assessed and reported as percentages. This study will assess the acceptability of the simulation-based training format for two scenarios involving an adolescent with autism, with or without intellectual disability, who displays aggressive and externalizing behaviors and the resulting change in confidence in managing clinical aggression. Two pediatric wards of similar size and patient complexity will be selected to participate in the study; they will be randomized to receive either simulation-based education plus web-based educational materials or the web-based educational materials only. Change in confidence will be assessed using pre- and posttraining surveys for bedside nursing staff exposed to the training and the control group who will receive the web-based training materials. Knowledge retention 3 months posttraining, as well as continued confidence and exposure to clinical aggression, will be assessed via surveys. Changes in confidence and competence will be compared statistically with the chi-square test using before-and-after data to compare the proportion of those who have high confidence between the two arms at baseline and at follow-up. The simulation-based education will be recorded with trained assessors reviewing participants’ abilities to de-escalate aggressive behaviors using a validated tool. This data will be analyzed using mean values and SDs to understand the variation in performance of individuals who undertake the training. Data from each participating ward will be collected during each shift for the duration of the study to assess the number of aggressive incidents and successful de-escalation for patients with ASD. Total change in Code Grey activations will also be assessed, with both datasets analyzed using descriptive statistics. Results: This study gained ethical approval from The Royal Children's Hospital Melbourne Human Research Ethics Committee (HREC) on November 1, 2019 (HREC reference number: 56684). Data collection was completed in February 2020. Data analysis is due to commence with results anticipated by August 2020. Conclusions: We hypothesize that this study is feasible to be conducted as a cluster RCT and that simulation-based training will be acceptable for acute care pediatric nurses. We anticipate that the intervention ward will have increased confidence in managing clinical aggression in children with ASD immediately and up to 3 months posttraining
Utility of CSF Cytokine/Chemokines as Markers of Active Intrathecal Inflammation: Comparison of Demyelinating, Anti-NMDAR and Enteroviral Encephalitis
(PUBLIC LIBRARY SCIENCE, 2016-08-30)
BACKGROUND: Despite the discovery of CSF and serum diagnostic autoantibodies in autoimmune encephalitis, there are still very limited CSF biomarkers for diagnostic and monitoring purposes in children with inflammatory or autoimmune brain disease. The cause of encephalitis is unknown in up to a third of encephalitis cohorts, and it is important to differentiate infective from autoimmune encephalitis given the therapeutic implications. AIM: To study CSF cytokines and chemokines as diagnostic biomarkers of active neuroinflammation, and assess their role in differentiating demyelinating, autoimmune, and viral encephalitis. METHODS: We measured and compared 32 cytokine/chemokines using multiplex immunoassay and APRIL and BAFF using ELISA in CSF collected prior to commencing treatment from paediatric patients with confirmed acute disseminated encephalomyelitis (ADEM, n = 16), anti-NMDAR encephalitis (anti-NMDAR E, n = 11), and enteroviral encephalitis (EVE, n = 16). We generated normative data using CSF from 20 non-inflammatory neurological controls. The sensitivity of CSF cytokine/chemokines to diagnose encephalitis cases was calculated using 95th centile of control values as cut off. We correlated CSF cytokine/chemokines with disease severity and follow up outcome based on modified Rankin scale. One-way hierarchical correlational cluster analysis of molecules was performed in different encephalitis and outcome groups. RESULTS: In descending order, CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10 had the best sensitivity (>79.1%) when all encephalitis patients were included. The combination of IL-6 and IFN-α was most predictive of inflammation on multiple logistic regression with area under the ROC curve 0.99 (CI 0.97-1.00). There were no differences in CSF cytokine concentrations between EVE and anti-NMDAR E, whereas ADEM showed more pronounced elevation of Th17 related (IL-17, IL-21) and Th2 (IL-4, CCL17) related cytokine/chemokines. Unlike EVE, heat map analysis showed similar clustering of cytokine/chemokine molecules in immune mediated encephalitis (ADEM and anti-NMDAR E). Th1 and B cell (CXCL13 and CXCL10) molecules clustered together in patients with severe encephalopathy at admission and worse disability at follow up in all encephalitis. There was no correlation between CSF neopterin and IFN-γ or IFN-α. CONCLUSION: A combination panel of cytokine/chemokines consisting of CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10 measured using multiplex immunoassay may be used to diagnose and monitor intrathecal inflammation in the brain. Given their association with worse outcome, certain key chemokines (CXCL13, CXCL10) could represent potential therapeutic targets in encephalitis.
Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU
Subtelomeric 1q43q44 microdeletions cause a syndrome associating intellectual disability, microcephaly, seizures and anomalies of the corpus callosum. Despite several previous studies assessing genotype-phenotype correlations, the contribution of genes located in this region to the specific features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17 patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations in HNRNPU and ZBTB18 to assess the contribution of each gene as well as the possibility of epistasis between genes. Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability. ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm and refine the complex genotype-phenotype correlations existing in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of AKT3, ZBTB18 and HNRNPU in humans.
Group A Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease: Epidemiology and Clinical Considerations.
(Springer Science and Business Media LLC, 2017-02)
OPINION STATEMENT: Early recognition of group A streptococcal pharyngitis and appropriate management with benzathine penicillin using local clinical prediction rules together with validated rapi-strep testing when available should be incorporated in primary health care. A directed approach to the differential diagnosis of acute rheumatic fever now includes the concept of low-risk versus medium-to-high risk populations. Initiation of secondary prophylaxis and the establishment of early medium to long-term care plans is a key aspect of the management of ARF. It is a requirement to identify high-risk individuals with RHD such as those with heart failure, pregnant women, and those with severe disease and multiple valve involvement. As penicillin is the mainstay of primary and secondary prevention, further research into penicillin supply chains, alternate preparations and modes of delivery is required.
Ethical Considerations for the Return of Incidental Findings in Ophthalmic Genomic Research
(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-01-01)
Whole genome and whole exome sequencing technologies are being increasingly used in research. However, they have the potential to identify incidental findings (IF), findings not related to the indication of the test, raising questions regarding researchers' responsibilities toward the return of this information to participants. In this study we discuss the ethical considerations related to the return of IF to research participants, emphasizing that the type of the study matters and describing the current practice standards. There are currently no legal obligations for researchers to return IF to participants, but some viewpoints consider that researchers might have an ethical one to return IF of clinical validity and clinical utility and that are actionable. The reality is that most IF are complex to interpret, especially since they were not the indication of the test. The clinical utility often depends on the participants' preferences, which can be challenging to conciliate and relies on participants' understanding. In summary, in the context of a lack of clear guidance, researchers need to have a clear plan for the disclosure or nondisclosure of IF from genomic research, balancing their research goals and resources with the participants' rights and their duty not to harm.
The Many Organisational Factors Relevant to Planning Change in Emergency Care Departments: A Qualitative Study to Inform a Cluster Randomised Controlled Trial Aiming to Improve the Management of Patients with Mild Traumatic Brain Injuries
(PUBLIC LIBRARY SCIENCE, 2016-02-04)
BACKGROUND: The Neurotrauma Evidence Translation (NET) Trial aims to design and evaluate the effectiveness of a targeted theory-and evidence-informed intervention to increase the uptake of evidence-based recommended practices for the management of patients who present to an emergency department (ED) with mild head injuries. When designing interventions to bring about change in organisational settings such as the ED, it is important to understand the impact of the context to ensure successful implementation of practice change. Few studies explicitly use organisational theory to study which factors are likely to be most important to address when planning change processes in the ED. Yet, this setting may have a unique set of organisational pressures that need to be taken into account when implementing new clinical practices. This paper aims to provide an in depth analysis of the organisational context in which ED management of mild head injuries and implementation of new practices occurs, drawing upon organisational level theory. METHODS: Semi-structured interviews were conducted with ED staff in Australia. The interviews explored the organisational context in relation to change and organisational factors influencing the management of patients presenting with mild head injuries. Two researchers coded the interview transcripts using thematic content analysis. The "model of diffusion in service organisations" was used to guide analyses and organisation of the results. RESULTS: Nine directors, 20 doctors and 13 nurses of 13 hospitals were interviewed. With regard to characteristics of the innovation (i.e. the recommended practices) the most important factor was whether they were perceived as being in line with values and needs. Tension for change (the degree to which stakeholders perceive the current situation as intolerable or needing change) was relatively low for managing acute mild head injury symptoms, and mixed for managing longer-term symptoms (higher change commitment, but relatively low change efficacy). Regarding implementation processes, the importance of (visible) senior leadership for all professions involved was identified as a critical factor. An unpredictable and hectic environment brings challenges in creating an environment in which team-based and organisational learning can thrive (system antecedents for innovation). In addition, the position of the ED as the entry-point of the hospital points to the relevance of securing buy-in from other units. CONCLUSIONS: We identified several organisational factors relevant to realising change in ED management of patients who present with mild head injuries. These factors will inform the intervention design and process evaluation in a trial evaluating the effectiveness of our implementation intervention.
Explaining culturally and linguistically diverse (CALD) parents' access of healthcare services for developmental surveillance and anticipatory guidance: qualitative findings from the 'Watch Me Grow' study
(BIOMED CENTRAL LTD, 2017-03-22)
BACKGROUND: Regular health visits for parents with young children provide an opportunity for developmental surveillance and anticipatory guidance regarding common childhood problems and help to achieve optimal developmental progress prior to school entry. However, there are few published reports from Australian culturally and linguistically diverse (CALD) communities exploring parents' experiences for accessing child health surveillance programs. This paper aims to describe and explain parental experiences for accessing developmental surveillance and anticipatory guidance for children. METHODS: Qualitative data was obtained from 6 focus groups (33 parents) and seven in-depth interviews of CALD parents recruited from an area of relative disadvantage in Sydney. Thematic analysis of data was conducted using an ecological framework. RESULTS: An overarching theme of "awareness-beliefs-choices" was found to explain parents' experiences of accessing primary health care services for children. "Awareness" situated within the meso-and macro-systems explained parents knowledge of where and what primary health services were available to access for their children. Opportunities for families to obtain this information existed at the time of birth in Australian hospitals, but for newly arrived immigrants with young children, community linkages with family and friends, and general practitioner (GPs) were most important. "Beliefs" situated within the microsystems included parents' understanding of their children's development, in particular what they considered to be "normal" or "abnormal". Parental "choices", situated within meso-systems and chronosystems, related to their choices of service providers, which were based on the proximity, continuity, purpose of visit, language spoken by the provider and past experience of a service. CONCLUSIONS: CALD parents have diverse experiences with primary health care providers which are influenced by their awareness of available services in the context of their duration of stay in Australia. The role of the general practitioner, with language concordance, suggests the importance of diversity within the primary care health workforce in this region. There is a need for ongoing cultural competence training of health professionals and provisions need to be made to support frequent use of interpreters at general practices in Australia.
Does a brief, behavioural intervention, delivered by paediatricians or psychologists improve sleep problems for children with ADHD? Protocol for a cluster-randomised, translational trial
(BMJ PUBLISHING GROUP, 2017-04-01)
INTRODUCTION: Up to 70% of children with attention-deficit/hyperactivity disorder (ADHD) experience sleep problems. We have demonstrated the efficacy of a brief behavioural intervention for children with ADHD in a large randomised controlled trial (RCT) and now aim to examine whether this intervention is effective in real-life clinical settings when delivered by paediatricians or psychologists. We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: Children aged 5-12 years with ADHD (n=320) are being recruited for this translational cluster RCT through paediatrician practices in Victoria and Queensland, Australia. Children are eligible if they meet criteria for ADHD, have a moderate/severe sleep problem and meet American Academy of Sleep Medicine criteria for either chronic insomnia disorder or delayed sleep-wake phase disorder; or are experiencing sleep-related anxiety. Clinicians are randomly allocated at the level of the paediatrician to either receive the sleep training or not. The behavioural intervention comprises 2 consultations covering sleep hygiene and standardised behavioural strategies. The primary outcome is change in the proportion of children with moderate/severe sleep problems from moderate/severe to no/mild by parent report at 3 months postintervention. Secondary outcomes include a range of child (eg, sleep severity, ADHD symptoms, quality of life, behaviour, working memory, executive functioning, learning, academic achievement) and primary caregiver (mental health, parenting, work attendance) measures. Analyses will address clustering at the level of the paediatrician using linear mixed effect models adjusting for potential a priori confounding variables. ETHICS AND DISSEMINATION: Ethics approval has been granted. Findings will determine whether the benefits of an efficacy trial can be realised more broadly at the population level and will inform the development of clinical guidelines for managing sleep problems in this population. We will seek to publish in leading international paediatric journals, present at major conferences and through established clinician networks. TRIAL REGISTRATION NUMBER: ISRCTN50834814, Pre-results.
Exploring the relationship between alpha-actinin-3 deficiency and obesity in mice and humans
(NATURE PUBLISHING GROUP, 2017-07-01)
Obesity is a worldwide health crisis, and the identification of genetic modifiers of weight gain is crucial in understanding this complex disorder. A common null polymorphism in the fast fiber-specific gene ACTN3 (R577X) is known to influence skeletal muscle function and metabolism. α-Actinin-3 deficiency occurs in an estimated 1.5 billion people worldwide, and results in reduced muscle strength and a shift towards a more efficient oxidative metabolism. The X-allele has undergone strong positive selection during recent human evolution, and in this study, we sought to determine whether ACTN3 genotype influences weight gain and obesity in mice and humans. An Actn3 KO mouse has been generated on two genetic backgrounds (129X1/SvJ and C57BL/6J) and fed a high-fat diet (HFD, 45% calories from fat). Anthropomorphic features (including body weight) were examined and show that Actn3 KO 129X1/SvJ mice gained less weight compared to WT. In addition, six independent human cohorts were genotyped for ACTN3 R577X (Rs1815739) and body mass index (BMI), waist-to-hip ratio-adjusted BMI (WHRadjBMI) and obesity-related traits were assessed. In humans, ACTN3 genotype alone does not contribute to alterations in BMI or obesity.
'right@home': a randomised controlled trial of sustained nurse home visiting from pregnancy to child age 2 years, versus usual care, to improve parent care, parent responsivity and the home learning environment at 2 years
(BMJ PUBLISHING GROUP, 2017-03-01)
INTRODUCTION: By the time children start school, inequities in learning, development and health outcomes are already evident. Sustained nurse home visiting (SNHV) offers a potential platform for families experiencing adversity, who often have limited access to services. While SNHV programmes have been growing in popularity in Australia and internationally, it is not known whether they can improve children's learning and development when offered via the Australian service system. The right@home trial aims to investigate the effectiveness of an SNHV programme, offered to women from pregnancy to child age 2 years, in improving parent care of and responsivity to the child, and the home learning environment. METHODS AND ANALYSIS: Pregnant Australian women (n=722) are identified after completing a screening survey of 10 factors known to predict children's learning and development (eg, young pregnancy, poor mental or physical health, lack of support). Consenting women-surveyed while attending clinics at 10 hospitals in Victoria and Tasmania-are enrolled if they report having 2 or more risk factors. The intervention comprises 25 home visits from pregnancy to 2 years, focusing on parent care of the child, responsivity to the child and providing a good quality home learning environment. The standard, universal, Australian child and family health service provides the comparator (control). Primary outcome measures include a combination of parent-reported and objective assessments of children's sleep, safety, nutrition, parenting styles and the home learning environment, including the Home Observation of the Environment Inventory and items adapted from the Longitudinal Study of Australian Children. ETHICS AND DISSEMINATION: This study is approved by the Royal Children's Hospital Human Research Ethics Committees (HREC 32296) and site-specific HRECs. The investigators and sponsor will communicate the trial results to stakeholders, participants, healthcare professionals, the public and other relevant groups via presentations and publications. TRIAL REGISTRATION NUMBER: ISRCTN89962120, pre-results.
Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences
BACKGROUND: Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue. METHODS AND RESULTS: We identified mild and isolated orotic aciduria in 11 unrelated individuals with diverse clinical signs and symptoms, the most common denominator being intellectual disability/developmental delay. Of note, none had blood count abnormalities, relevant hyperammonemia or altered plasma amino acid profile. All individuals were found to have heterozygous alterations in UMPS. Four of these variants were predicted to be null alleles with complete loss of function. The remaining variants were missense changes and predicted to be damaging to the normal encoded protein. Interestingly, family screening revealed heterozygous UMPS variants in combination with mild orotic aciduria in 19 clinically asymptomatic family members. CONCLUSIONS: We therefore conclude that heterozygous UMPS-mutations can lead to mild and isolated orotic aciduria without clinical consequence. Partial UMPS-deficiency should be included in the differential diagnosis of mild orotic aciduria. The discovery of heterozygotes manifesting clinical symptoms such as hypotonia and developmental delay are likely due to ascertainment bias.
A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics.
(Elsevier BV, 2013-10-03)
Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.