ORCID Profile
0000-0002-2940-6886
Current Organisations
University of Western Australia
,
Telethon Kids Institute
,
Perth Children's Hospital
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Publisher: Wiley
Date: 30-03-2015
DOI: 10.1111/RESP.12521
Abstract: In iduals with cystic fibrosis (CF) suffer progressive airway inflammation, infection and lung damage. Airway inflammation and infection are present from early in life, often before children are symptomatic. CF gene mutations cause changes in the CF transmembrane regulator protein that result in an aberrant airway microenvironment including airway surface liquid (ASL) dehydration, reduced ASL acidity, altered airway mucin and a dysregulated inflammatory response. This review discusses how an altered microenvironment drives CF lung disease before overt airway infection, the response of the CF airway to early infection, and methods to prevent inflammation and early lung disease.
Publisher: Elsevier BV
Date: 10-2021
Publisher: American Thoracic Society
Date: 11-2018
Publisher: Frontiers Media SA
Date: 28-03-2019
Publisher: European Respiratory Society (ERS)
Date: 30-06-2010
Publisher: Research Square Platform LLC
Date: 08-09-2021
DOI: 10.21203/RS.3.RS-860700/V1
Abstract: ATP Binding Cassette Subfamily A Member 3 (ABCA-3) is a lipid transporter protein highly expressed in type-II alveolar (AT-II) cells. Mutations in ABCA3 can result in severe respiratory disease in infants and children. To study ABCA-3 deficiency in vitro , primary AT-II cells would be the cell culture of choice although s le accessibility is limited. Our aim was to investigate the suitability of primary nasal epithelial cells, as a surrogate culture model for AT-II cells, to study ABCA-3 deficiency. Expression of ABCA3 , and surfactant protein genes, SFTPB and SFTPC , was detected in primary nasal epithelial cells but at a significantly lower level than in AT-II cells. ABCA-3, SP-B and SP-C were detected by immunofluorescence microscopy in primary nasal epithelial cells. However, SP-B and SP-C were undetectable in primary nasal epithelial cells using western blot. Structurally imperfect lamellar bodies were observed in primary nasal epithelial cells using transmission electron microscopy. Functional assessment of the ABCA-3 protein demonstrated that higher concentrations of doxorubicin reduced cell viability in ABCA-3 deficient nasal epithelial cells compared to controls in an assay-dependent manner. Our results indicate that there may be a role for primary nasal epithelial cell cultures to model ABCA-3 deficiency in vitro although additional cell culture models that more effectively recapitulate the AT-II phenotype may be required.
Publisher: Wiley
Date: 10-03-2023
DOI: 10.1002/PPUL.26377
Abstract: Addressing the recognized challenges and inequalities in providing high quality healthcare for rare diseases such as children's interstitial lung disease (chILD) requires collaboration across institutional, geographical, discipline, and system boundaries. The Children's Interstitial Lung Disease Respiratory Network of Australia and New Zealand (chILDRANZ) is an ex le of a clinical network that brings together multidisciplinary health professionals for collaboration, peer learning, and advocacy with the goal of improving the diagnosis and management of this group of rare and ultra‐rare conditions. This narrative review explores the multifaceted benefits arising from social learning spaces within rare disease clinical networks by applying the value creation framework. The operation of the chILDRANZ network is used as an ex le across the framework to highlight how value is generated, realized, and transferred within such collaborative clinical and research networks. The community of practice formed in the chILDRANZ multidisciplinary meetings provides a strong ex le of social learning that engages with the uncertainty inherent in rare disease diagnosis and management and pays attention to generate new knowledge and best practice to make a difference for children and families living with chILD. This review underscores international calls for further investment in, and support of, collaborative clinical networks and virtual centers of excellence for rare disease.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.PRRV.2021.06.002
Abstract: Asthma is the most common chronic lung disease in childhood. There has been a significant worldwide effort to develop tools/methods to identify children's risk for asthma as early as possible for preventative and early management strategies. Unfortunately, most childhood asthma prediction tools using conventional statistical models have modest accuracy, sensitivity, and positive predictive value. Machine learning is an approach that may improve on conventional models by finding patterns and trends from large and complex datasets. Thus far, few studies have utilized machine learning to predict asthma in children. This review aims to critically assess these studies, describe their limitations, and discuss future directions to move from proof-of-concept to clinical application.
Publisher: Springer Science and Business Media LLC
Date: 06-04-2022
DOI: 10.1038/S41598-022-09463-8
Abstract: Diagnosis of chronic disease in a child can result in unresolved grief (UG) in parents. This study aimed to evaluate the efficacy of psychological insight-oriented therapy (IOT) as a treatment for UG compared to disease related education in parents of children with cystic fibrosis (CF). Sequence of delivery, first IOT then disease related education (or vice versa) was also examined, to let all participants experience both interventions. Parents were screened for UG. Parents with UG were randomised to either five 1-h sessions of IOT or five 1-h sessions of education. Measures were assessed pre-intervention, after the first intervention period (primary efficacy assessment), and after the second intervention period (swapping intervention). Forty-seven parents were screened of which 46.8% (22/47) had UG. Median duration of UG was 5 years (range: 6 months–14 years). Anxiety (50% vs. 20%, p = 0.03) and stress (59% vs. 28%, p = 0.03) were significantly more prevalent in parents with UG. There was no difference between arms in the odds of UG resolving either following the first intervention period (OR 0.88 95% CI 0.5, 1.5) or the second intervention period (OR 0.91 95% CI 0.5, 1.6). While not statistically significant, adjusted mean values for seven of the eight mental health measures were lower in the IOT (first) arm compared to the ED (first) arm, following the first intervention period. UG is a significant burden for families affected by CF. Provision of disease related education and psychological support, regardless of sequence, can result in resolution of grief. Trial registration number: ACTRN12621000796886, date of registration 24/06/2021, retrospectively registered.
Publisher: Wiley
Date: 29-07-2016
DOI: 10.1002/PPUL.23260
Abstract: We present a case of an infant born at almost 28 weeks gestation, found to be homozygous for a missense mutation of ABCA3, with diffuse lung disease that has continued throughout infancy. The patient's clinical course and chest imaging was highly suggestive of diffuse lung disease of infancy, and not of chronic lung disease of prematurity. The lung disease proved to be highly responsive to systemic corticosteroids. This is a case of ABCA3 lung disease that demonstrated improvement after systemic glucocorticosteroid administration.
Publisher: Springer Science and Business Media LLC
Date: 29-12-2022
DOI: 10.1186/S12890-022-02219-0
Abstract: In children, chronic wet cough may be a sign of underlying lung disease, including protracted bacterial bronchitis (PBB) and bronchiectasis. Chronic ( 4 weeks in duration) wet cough (without indicators pointing to alternative causes) that responds to antibiotic treatment is diagnostic of PBB. Timely recognition and management of PBB can prevent disease progression to irreversible bronchiectasis with lifelong consequences. However, detection and management require timely health-seeking by carers and effective management by clinicians. We aim to improve (a) carer health-seeking for chronic wet cough in their child and (b) management of chronic wet cough in children by clinicians. We hypothesise that implementing a culturally integrated program, which is informed by barriers and facilitators identified by carers and health practitioners, will result in improved lung health of First Nations children, and in the future, a reduced the burden of bronchiectasis through the prevention of the progression of protracted bacterial bronchitis to bronchiectasis. This study is a multi-centre, pseudorandomised, stepped wedge design. The intervention is the implementation of a program. The program has two components: a knowledge dissemination component and an implementation component. The implementation is adapted to each study site using a combined Aboriginal Participatory Action Research and an Implementation Science approach, guided by the Consolidated Framework of Implementation Research. There are three categories of outcome measures related to (i) health (ii) cost, and (iii) implementation. We will measure health-seeking as the proportion of parents seeking help for their child in a 6-month period before the intervention and the same 6-month period (i.e., the same six calendar months) thereafter. The parent-proxy, Cough-specific Quality of Life (PC-QoL) will be the primary health-related outcome measure. We hypothesise that a tailored intervention at each site will result in improved health-seeking for carers of children with a chronic wet cough and improved clinician management of chronic wet cough. In addition, we expect this will result in improved lung health outcomes for children with a chronic wet cough. Australian New Zealand Clinical Trials Registry ACTRN12622000430730 , registered 16 March 2022, Retrospectively registered.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2021
DOI: 10.1186/S12961-021-00773-3
Abstract: The purpose of this paper is to highlight a perspective for decolonizing research with Australian First Nations and provide a framework for successful and sustained knowledge translation by drawing on the recent work conducted by a research group, in five remote communities in North-Western Australia. The perspective is discussed in light of national and international calls for meaningful and dedicated engagement with First Nations people in research, policy and practice, to help close the health gap between First Nations and other Australians.
Publisher: Springer Science and Business Media LLC
Date: 06-2016
DOI: 10.1007/S00431-016-2738-2
Abstract: The importance of good device technique to maximise delivery of aerosolised medications is widely recognised. Pressurised metered dose inhaler (pMDI)-spacer technique was investigated in 122 children, aged 2-7 years, with asthma. Eight in idual steps of device technique were evaluated before and after viewing an instructional video for correct device technique. Video measurements were repeated every three months for nine months. Device technique improved directly after video instruction at the baseline study visit (p < 0.001) but had no immediate effect at subsequent visits. Additionally, pMDI-spacer technique improved with successive visits over one year for the group overall as evidenced by increases in the proportion of children scoring maximal (p = 0.02) and near-maximal (p = 0.04) scores. Repeated video instruction over time improves inhaler technique in young children. • Correct device technique is considered essential for sufficient delivery of inhaled medication. • Poor inhaler use is common in young asthmatic children using pressurised metered dose inhalers and spacers. What is New: • Video instruction could be used as a strategy to improve device technique in young children.
Publisher: BMJ
Date: 09-2007
Publisher: Springer Science and Business Media LLC
Date: 08-2017
DOI: 10.1038/S41467-017-00532-5
Abstract: Modulation of airway surface liquid (ASL) pH has been proposed as a therapy for cystic fibrosis (CF). However, evidence that ASL pH is reduced in CF is limited and conflicting. The technical challenges associated with measuring ASL pH in vivo have precluded accurate measurements in humans. In order to address this deficiency, ASL pH was measured in vivo in children using a novel luminescent technology integrated with fibre-optic probes. Here we show that ASL pH in children with CF is similar to that of children without CF. Findings were supported by highly controlled direct pH measurements in primary human airway epithelial cell culture models, which also suggest that the potential ASL pH gradient produced by defective apical ion transport is balanced out by paracellular shunting of acid/base. Thus, reduced baseline ASL pH is unlikely to be an important pathobiological factor in early CF lung disease.
Publisher: Wiley
Date: 05-09-2017
DOI: 10.1111/ANAE.14011
Abstract: Inhalation of aerosolised medications are the mainstay of treatment for a number of chronic lung diseases and have several advantages over systemically-administered medications. These include more rapid onset of action for drugs such as β-adrenergic agonists when compared with oral medication, high luminal doses for inhaled antibiotics when used to treat endobronchial infection, and an improved therapeutic index compared with systemic delivery for these and other classes of drugs such as corticosteroids. The use of aerosolised drugs to treat patients whose tracheas are intubated is less well established, in part because systemic delivery via the intravenous route can be a simpler alternative for many drugs. Consequently, research in this area is largely limited to a number of in vitro studies and very few clinical trials. Unfortunately, a lack of focus in this area has resulted in a number of practices which at best are ineffective, and at worst dangerous for the patient. Although there have been some attempts to re-invigorate research in order to improve delivery systems, current devices are, to a great extent, based on long-standing technology developed more than 50 years ago. In this review, we explore current knowledge and provide guidance as to when and how the inhaled route may be of value when treating patients whose tracheas are intubated, and we set out the challenges facing those attempting to advance the topic. We conclude by reviewing current areas of interest that may lead to more effective and widespread use of aerosols in the treatment of intubated patients.
Publisher: Wiley
Date: 08-12-2009
DOI: 10.1111/J.1651-2227.2009.01508.X
Abstract: A recently proposed method for classifying preschool wheeze is to describe it as either episodic (viral) wheeze or multiple trigger wheeze. In research studies, phenotype is generally determined by retrospective questionnaire. To determine whether recently proposed phenotypes of preschool wheeze are stable over time. In all, 132 two to six-year-old children with doctor diagnosed asthma on maintenance inhaled corticosteroids were classified as having episodic (viral) wheeze or multiple trigger wheeze at a screening visit and then followed up at three-monthly intervals for a year. At each follow-up visit, standardized questionnaires were used to determine whether the subjects wheezed only with, or also in the absence of colds. Stability of the phenotypes was assessed at the end of the study. Phenotype as determined by retrospective parental report at the start of the study was not predictive of phenotype during the study year. Phenotypic classification remained the same in 45.9% of children and altered in 54.1% of children. When children with preschool wheeze are classified into episodic (viral) wheeze or multiple trigger wheeze based on retrospective questionnaire, the classification is likely to change significantly within a 1-year period.
Publisher: Mary Ann Liebert Inc
Date: 10-2010
Abstract: Output from spacers (or valved holding chambers) is sensitive to changes in breathing pattern. Different spacers have unique characteristics that may influence breathing. A method used for breathing simulation, where the simulated breathing can be recorded on subjects while they are using spacers, may allow for more accurate in vitro estimation of drug delivery in specific populations, using specific spacers. A flow chamber was used to record breathing while salbutamol was administered to two adult subjects through different spacers. Each subject performed a series of breathing patterns over a range of different inhalation volumes and flows. Salbutamol "inhaled" by subjects was captured on inspiratory filters and quantified by ultraviolet spectrophotometry. Recorded breathing patterns were simulated and ex vivo drug delivery was compared to in vitro drug delivery. Three equipment configurations were used to validate different aspects of the methodology. Configuration 1: breathing recorded by pneumotachometer placed directly between a human subject and the spacer. Breathing simulation performed with an identical setup. Configuration 2: spacer enclosed within a flow-chamber while breathing was recorded. Breathing simulation performed with an identical setup. Configuration 3: spacer enclosed in flow chamber to record breathing, but not when simulating breathing. In each configuration, the ex vivo and in vitro (simulated) filter doses were compared. Configuration 1: the median difference between ex vivo and in vitro filter doses was 0.4% (range: -12.2 to 6.9%). Configuration 2: the median difference was -2.3% (range: -9.0 to 5.0%). Configuration 3: the median difference was 1.7% (range: -11.5 to 3.9%). Our results indicate that in vitro simulated drug delivery using this method of recording using a flow chamber, closely approximates ex vivo total drug delivery. This technique allows for recording of breathing on patients while they are using spacers, with minimum increase in dead space or resistance, and no physical alteration in the patient-device interface.
Publisher: Springer Science and Business Media LLC
Date: 06-02-2018
Publisher: Springer Science and Business Media LLC
Date: 1988
DOI: 10.1007/BF00614558
Abstract: The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a ersity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome.
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.PRRV.2011.01.008
Abstract: Accumulating evidence suggest that splitting preschool recurrent wheezing disorders into Episodic (Viral) Wheeze (EVW) and Multiple Trigger Wheeze (MTW) is an oversimplification. There is little evidence that the EVW and MTW phenotypes are related to the longitudinal patterns of wheeze, or to different underlying pathological processes. As the clinical response to inhaled corticosteroids and montelukast varies considerably between in idual children with EVW, and between in idual patients with MTW, the clinical usefulness of the EVW-MTW approach is doubtful. Based on the currently available evidence, we propose to describe preschool wheeze symptoms not only in terms of temporal pattern, but also in terms of frequency and severity, and age of onset. Relevant associated clinical parameters like atopy and eczema should be described with recognition of age of onset, pattern, and severity. Comparing these data to biomarkers and histopathology may help to improve our understanding of preschool wheezing disorders in the future. Until phenotypes can be described that are associated with different pathobiological process, are related to different longitudinal outcomes, or are clearly different in terms of response to therapy, clinicians are encouraged to take a trial and error approach of different therapeutic agents in preschool children with troublesome recurrent wheeze.
Publisher: European Respiratory Society (ERS)
Date: 10-2019
DOI: 10.1183/23120541.00248-2019
Abstract: Chronic wet cough, the most common symptom of a disease spectrum that encompasses protracted bacterial bronchitis (PBB) and bronchiectasis, is common among Aboriginal children. In the absence of any community prevalence data, and with the high burden of respiratory disease and the European Respiratory Society task force's recommendation to identify disease burden, we determined the prevalence of chronic wet cough and PBB in young Aboriginal children in four remote communities in north Western Australia. A whole-population, prospective study was conducted. Aboriginal children aged ≤7 years were clinically assessed for chronic wet cough by paediatric respiratory clinicians between July 2018 and May 2019. Where children had a wet cough but parents reported a short or uncertain cough duration, children were followed up 1 month later. A medical record audit 6 weeks to 3 months later was used to determine those children with chronic wet cough who had PBB (based on response to antibiotics). Of the 203 children, 191 (94% median age 3.5 years, range 0–7 years) were enrolled. At the initial visit, chronic wet cough was present in 21 (11%), absent in 143 (75%) and unknown in 27 (14%). By follow-up, the total prevalence of chronic wet cough was 13% (95% CI 8–19%) and 10% (95% CI 7–17%) for PBB. Chronic wet cough was more common in the two communities with unsealed roads (19%) compared to the two with sealed roads (7%). Given the relatively high prevalence, strategies to address reasons for and treatment of chronic wet cough and PBB in young Aboriginal children in remote north Western Australia are required.
Publisher: Wiley
Date: 21-01-2019
DOI: 10.1002/PPUL.24249
Abstract: Structural lung changes seen on computed tomography (CT) scans in Cystic Fibrosis (CF) and Primary Ciliary Dyskinesia (PCD) are currently described using scoring systems derived from CF populations. This practise assumes lung damage in the two conditions is identical, potentially resulting in a failure to identify PCD-specific changes. Our study addresses this assumption. A total of 58 CT scans from 41 PCD patients (age 2-48 years) were examined and the presence and extent of abnormalities common in CF bronchiectasis, bronchial wall thickening, atelectasis, mucous plugging, and air trapping noted. Further assessment of the PCD scans by an experienced chest radiologist identified several unique PCD specific changes. Bronchial wall thickening was the commonest abnormality seen in PCD. All abnormalities were present more often in middle and lower lobes than in upper lobes (P < 0.001). Bronchiectasis, mucus plugging, atelectasis, and air trapping were present more often in PCD than in the historic CF cohorts which formed the basis of two CF scoring systems (P < 0.05). Extensive tree-in-bud pattern of mucus plugging, thickening of interlobar, and interlobular septa, and whole lobe atelectasis were seen significantly more frequently in PCD than CF. Structural changes identified on CT scans in PCD are not identical to those previously described in CF patients and suggest assessment of PCD structural changes on CT should not use CF derived scoring systems.
Publisher: BMJ
Date: 05-2022
DOI: 10.1136/BMJRESP-2022-001236
Abstract: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance. We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance. Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians. ACTRN12619000564156.
Publisher: Wiley
Date: 25-07-2019
DOI: 10.1111/RESP.13642
Abstract: Chronic lung disease is prevalent among Australian Aboriginal children. Chronic wet cough is an early marker of disease but often goes undetected. Currently, no studies have examined health practitioner knowledge of chronic wet cough. We set out to examine health practitioner knowledge of chronic wet cough and chronic lung disease in Aboriginal children and to identify barriers and enablers to effective management. A qualitative study, gathering data through in idual semi-structured, in-depth interviews and focus groups to ascertain health practitioner knowledge about management of Aboriginal children with chronic wet cough in a regional Kimberley town and remote community. Thirty-seven health practitioners participated. Key barriers identified were: (i) limited training in assessment and management of chronic wet cough (ii) prioritization of acute presentations and competing complex chronic conditions and (iii) normalization of cough in children by health practitioners. Key enablers were: (i) improving practitioners' knowledge and expertise in managing chronic wet cough and (ii) health system changes to facilitate longitudinal patient care, improved cultural competence, improved chronic disease management and post-hospitalization follow-up. Key barriers to effective management of chronic wet cough are limited training in chronic wet cough management combined with competing complexities of both acute and chronic healthcare needs for Aboriginal families. Early detection and management of chronic wet cough in Aboriginal children can be facilitated through health practitioner training, access to standardized management guidelines and a service model that allows longitudinal patient follow-up and resources to effectively prevent and manage chronic lung disease in children.
Publisher: Springer Science and Business Media LLC
Date: 29-07-2019
Publisher: BMJ
Date: 02-2022
DOI: 10.1136/BMJRESP-2021-001139
Abstract: Research is needed to determine best practice for genomic testing in the context of child interstitial or diffuse lung disease (chILD). We explored parent’s and child’s health-related quality of life (HRQoL), parents’ perceived understanding of a genomic testing study, satisfaction with information and the study and decisional regret to undertake genomic testing. Parents of children with diagnosed or suspected chILD who were enrolled in a genomic sequencing study were invited to complete questionnaires pretesting (T1) and after receiving the result (T2). Parents’ (T1, n=19 T2, n=17) HRQoL was lower than population norms. Study satisfaction (T1) and perceived understanding (T2) were positively correlated (r s =0.68, p=0.014). Satisfaction with information (T1 and T2) and decisional regret (T2) were negatively correlated (T1 r s =−0.71, p=0.01 T2 r s =−0.56, p=0.03). Parents reported wanting more frequent communication with staff throughout the genomic sequencing study, and greater information about the confidentiality of test results. Understanding of genomic testing, satisfaction with information and participation and decisional regret are inter-related. Pretest consultations are important and can allow researchers to explain confidentiality of data and the variable turnaround times for receiving a test result. Staff can also update parents when there will be delays to receiving a result.
Publisher: Wiley
Date: 23-09-2022
DOI: 10.1002/PPUL.26148
Abstract: The burden of bronchiectasis is disproportionately high in Aboriginal adults, with early mortality. Bronchiectasis precursors, that is, protracted bacterial bronchitis (PBB) and chronic suppurative lung disease (CSLD), often commence in early childhood. We previously reported a 10% prevalence of PBB in Aboriginal children aged 0 to 7 years, however there are no data on prevalence of chronic lung diseases in older children. Our study aimed to determine the prevalence of PBB, CSLD, bronchiectasis, and asthma in Aboriginal children living in four communities. A whole‐population cross‐sectional community co‐designed study of Aboriginal children aged ‐years in four remote communities in Western Australia across two‐time points, a month apart. Children were assessed by pediatric respiratory clinicians with spirometry undertaken (when possible) between March–September 2021. Children with respiratory symptoms were followed up via medical record audit from either the local medical clinic or via a respiratory specialist clinic through to March 2022 to establish a final diagnosis. We recruited 392 (91.6%) of those in the selected communities median age = 8.4 years (interquartile range [IQR] 5.1–11.5). Seventy children (17.9%) had a chronic respiratory pathology or abnormal spirometry results. PBB was confirmed in 30 (7.7%), CSLD = 13 (3.3%), bronchiectasis = 5 (1.3%) and asthma = 17 (4.3%). The prevalence of chronic wet cough significantly increased with increasing age. The prevalence of PBB, CSLD and bronchiectasis is high in Aboriginal children and chronic wet cough increases with age. This study highlights the high disease burden in Aboriginal children and the urgent need for strategies to address these conditions.
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: Elsevier BV
Date: 09-2019
Publisher: Wiley
Date: 09-07-2019
DOI: 10.1002/PPUL.24445
Publisher: Wiley
Date: 18-03-2019
DOI: 10.1002/PPUL.24286
Abstract: Increasing evidence suggests the forced oscillation technique (FOT) has the capacity to provide non-invasive monitoring and diagnosis of respiratory disease in young children. However, which FOT outcomes provide the most pertinent clinical information is currently unknown. The aim of this study was to determine which FOT outcomes were most sensitive for differentiating between health and specific childhood respiratory disease. Respiratory impedance was measured using a commercial device (i2M, Chess Medical, Belgium) in children aged between 3 and 7 years, who had been diagnosed with either cystic fibrosis (N = 84), asthma (N = 99) or were born very preterm (N = 114). Z-scores were calculated for respiratory system resistance (Rrs) and reactance (Xrs) at 6, 8, and 10 Hz, the resonance frequency (Fres), frequency dependence (Fdep The FOT outcomes best able to discern between health and disease were Fres (P < 0.0001) in cystic fibrosis, Fres (P < 0.0001) in asthma and Xrs
Publisher: Informa UK Limited
Date: 12-07-2010
Publisher: Wiley
Date: 16-11-2021
DOI: 10.1111/JPC.15818
Abstract: Establishing the underlying cause in a child with chronic suppurative lung disease (CSLD) allows for targeted treatment and screening for associated complications. One cause of CSLD is primary ciliary dyskinesia (PCD). Testing for PCD requires specialist expertise which is not widely available. Computed tomography (CT) scans are commonly performed when assessing CSLD. Identifying PCD‐specific signs on CT would help clinicians in deciding when to refer for specialist testing. One potential PCD‐specific sign we have observed is fissure adjacent partial lobe atelectasis (FAPLA). We aimed to assess if FAPLA is commonly found in CT of PCD patients. Fifty‐eight CT scans from 42 adult and child PCD patients were analysed. The presence and distribution of FAPLA were noted, and its association to sputum culture and other signs commonly seen in CSLD (bronchiectasis, bronchial wall thickening, air trapping and mucus plugging). FAPLA was found in 13 of 40 participants in their earliest CT scan. The prevalence of FAPLA was similar in children and adults. FAPLA involved the right middle lobe in all 13 cases and was systematically associated with ≥1 other structural change. There was no association between FAPLA and bacterial isolation from sputum. FAPLA was found in 32.5% PCD scans, without difference between children and adults in terms of frequency. Future work will determine if it is a PCD‐specific sign by assessing whether it is also found in other CSLD processes and analysing more scans from children with PCD to determine how early this sign develops.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JCF.2021.11.010
Abstract: Treatment for pulmonary exacerbations of cystic fibrosis (CF) can produce a range of positive and negative outcomes. Understanding which of these outcomes are achievable and desirable to people affected by disease is critical to agreeing to goals of therapy and determining endpoints for trials. The relative importance of outcomes resulting from treatment of these episodes are not reported. We aimed to (i) quantify the relative importance of outcomes resulting from treatment for pulmonary exacerbations and (ii) develop patient and proxy carer-reported weighted outcome measures for use in adults and children, respectively. A discrete choice experiment (DCE) survey was conducted. Participants were asked to make a series of hypothetical decisions about treatment for pulmonary exacerbations to assess how they make trade-offs between different attributes of health. Data were analysed using a conditional logistic regression model. The correlation coefficients from these data were rescaled to enable generation of a composite health outcome score between 0 and 100 (worst to best health state). 362 in iduals participated (167 people with CF and 195 carers) of these, 206 completed the survey (56.9%). Most participants were female and resided in Australia. Difficult ainful breathing had the greatest impact on the preferred health state amongst people with CF and carers alike. Avoidance of gastrointestinal problems also heavily influenced decision-making. These data should be considered when making treatment decisions and determining endpoints for trials. Further research is recommended to quantify the preferences of children and to determine whether these align with those of their carer(s).
Publisher: American Thoracic Society
Date: 15-03-2020
Publisher: Wiley
Date: 11-2012
Publisher: Elsevier BV
Date: 06-2018
Publisher: Wiley
Date: 27-09-2022
DOI: 10.1002/NOP2.1380
Abstract: The aims of the study were to investigate family and hospital staff views about the use of spring‐infusor devices for administration of intravenous antibiotic medications, to examine if the device is acceptable and feasible and to map a process for implementation. A qualitative study with a pragmatist approach, within a larger, mixed methods knowledge translation study. Data were collected by semi‐structured interviews with patients who have cystic fibrosis and their parents and focus groups and interviews with hospital staff. Interviews were concluded when no new themes were identified. Thematic analysis and process mapping was undertaken. Six parents, nine children and 30 staff were interviewed. Families preferred spring‐infusors. Staff knowledge, experience and attitudes toward spring‐infusor use was varied. All staff acknowledged that their role is to support patient‐centred care. Spring‐infusors are preferred by families and clinicians above other IV administration devices but misconceptions about spring‐infusor use and numerous procedural challenges reduced their use.
Publisher: Springer Berlin Heidelberg
Date: 2011
Publisher: IEEE
Date: 12-2019
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.PRRV.2018.03.002
Abstract: Interstitial lung disease in children (chILD) comprises a range of different rare diseases. There is limited evidence for the treatment of chILD and no randomised clinical trials of treatment have been undertaken. Most treatments are therefore prescribed off-label based on expert opinion. The off-label nature of prescription of drugs for chILD highlights the importance of a solid understanding of the side effects to facilitate risk-benefit assessment. The European Respiratory Society chILD guidelines recommend the use of systemic glucocorticosteroids, hydroxychloroquine and azithromycin. Side effects of these drugs will be discussed followed by consideration of other drugs used for the treatment of chILD.
Publisher: Elsevier BV
Date: 04-2019
Publisher: American Academy of Pediatrics (AAP)
Date: 12-2010
Abstract: The goal was to determine the number of breaths required to inhale salbutamol from different spacers/valved holding chambers (VHCs). Breathing patterns were recorded for 2- to 7-year-old children inhaling placebo from 4 different spacers/VHCs and were simulated by a flow generator. Drug delivery with different numbers of tidal breaths and with a single maximal breath was compared. With tidal breathing, mean inhalation volumes were large, ranging from 384 mL to 445 mL. Mean values for drug delivery with an Aerochamber Plus (Trudell, London, Canada) were 40% (95% confidence interval [CI]: 34%–46%) and 41% (95% CI: 36%–47%) of the total dose with 2 and 9 tidal breaths, respectively. Mean drug delivery values with these breath numbers with a Funhaler (Visiomed, Perth, Australia) were 39% (95% CI: 34%–43%) and 38% (95% CI: 35%–42%), respectively. With a Volumatic (GlaxoSmithKline, Melbourne, Australia), mean drug delivery values with 2 and 9 tidal breaths were 37% (95% CI: 33%–41%) and 43% (95% CI: 40%–46%), respectively (P = .02) there was no significant difference in drug delivery with 3 versus 9 tidal breaths. With the modified soft drink bottle, drug delivery. Drug delivery was not improved with a single maximal breath with any device. For young children, tidal breaths through a spacer/VHC were much larger than expected. Two tidal breaths were adequate for small-volume VHCs and a 500-mL modified soft drink bottle, and 3 tidal breaths were adequate for the larger Volumatic VHC.
Publisher: Wiley
Date: 17-07-2018
DOI: 10.1113/JP275426
Publisher: Wiley
Date: 06-2019
DOI: 10.1111/IMJ.14158
Abstract: The inter-jurisdictional National Mutual Acceptance (NMA) scheme for Human Research Ethics Committee (HREC) approvals of human research is designed to reduce the reported delays and costs of ethical review. Introduction of the NMA set forth an uncoupling of the ethics and governance review processes, permitting a single ethical review for multiple sites, while continuing separate governance review for each centre covering financial and operational aspects of the research project. To compare the time required to gain ethics and governance approvals in Australia for a non-interventional investigator-led study from December 2015 to approval times for an earlier pre-NMA study utilising a similar study design and study sites and evaluate the effect that the NMA has had on total approval time for non-interventional multi-centre projects. We recorded the time taken to obtain ethics and governance approval at 16 sites for our nationwide low-risk non-interventional study looking at the prevalence and aetiology of non-tuberculous mycobacterial infection in people with cystic fibrosis in Australia. Applications were submitted to three hospitals and one university HREC to conduct our study at 16 hospital sites, HREC approval took from 16 to 79 days (median 28). Subsequent site-specific governance approval at 15 hospital sites took 23-225 days (median 83). The entire process of gaining ethical and governance approval to conduct the study at 16 sites took 24 months at an estimated cost of AU$56000 (US$ 42 000). Lengthy governance approval processes negate benefits gained from centralised ethics review under the NMA.
Publisher: BMJ
Date: 15-07-2021
DOI: 10.1136/ARCHDISCHILD-2020-321546
Abstract: High-flow nasal oxygen (HFNO) is frequently used in hospitals, producing droplets and aerosols that could transmit SARS-CoV-2. To determine if a headbox could reduce droplet and aerosol transmission from patients requiring HFNO. The size and dispersion of propylene glycol (model for patient-derived infectious particles) was measured using a spectrometer and an infant mannequin receiving 10–50 L/min of HFNO using (1) no headbox, (2) open headbox, (3) headbox-blanket or (4) headbox with a high-efficiency particulate (HEP) filter covering the neck opening. All headbox set-ups reduced the dispersal of droplets and aerosols compared with no headbox. The headbox-blanket system increased aerosol dispersal compared with the open headbox. The fraction of aerosols retained in the headbox for HFNO of 10 and 50 L/min was, respectively, as follows: (1) open headbox: 82.4% and 42.2% (2) headbox-blanket: 56.8% and 39.5% (3) headbox-HEP filter: 99.9% and 99.9%. A HEP-filter modified headbox may serve as an effective droplet and aerosol barrier adjunct for the protection of staff caring for children receiving HFNO.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.PRRV.2015.05.004
Abstract: Biomarkers in cystic fibrosis are used i. for the measurement of cystic fibrosis transmembrane regulator function in order to diagnose cystic fibrosis, and ii. to assess aspects of lung disease severity (e.g. inflammation, infection). Effective biomarkers can aid disease monitoring and contribute to the development of new therapies. The tests of cystic fibrosis transmembrane regulator function each have unique strengths and weaknesses, and biomarkers of inflammation, infection and tissue destruction have the potential to enhance the management of cystic fibrosis through the early detection of disease processes. The development of biomarkers of cystic fibrosis lung disease, in particular airway inflammation and infection, is influenced by the challenges of obtaining relevant s les from infants and children for whom early detection and treatment of disease might have the greatest long term benefits.
Publisher: Elsevier BV
Date: 07-2020
DOI: 10.1016/J.JCF.2019.08.005
Abstract: Recent standards of care mention chest radiography (CR) but not chest computed tomography (CT) in routine annual follow-up of children with cystic fibrosis (CF). To minimise radiation risk, CT or CR should only be performed if they impact clinical decision making. We investigated whether in addition to a wide range of commonly used clinical parameters, chest CT and/or CR in routine follow-up of CF patients influence clinical decisions. 36 web based clinical vignettes (i.e. case simulations) were designed using clinical data from patients aged 8-18 years, randomly selected from two CF centres in The Netherlands. In a randomized cross-over design, clinicians assessed eight vignettes and suggested therapeutic/diagnostic management on two occasions, with a ten-week interval. Radiological information (CT or CR) was included at only one of the two assessments, in random order. Any differences in management could be attributed to information from CT or CR, and were compared by McNemar analysis. 44 European and Australian clinicians completed a total of 143 CT vignette pairs and 167 CR vignette pairs. CT was associated with a significant increase in antifungal treatment (Risk Ratio (RR) 2.8 (1.3-6.0, p = .02)), bronchoscopies (RR 1.6 (1.1-2.5, p = .04)), mycobacterial cultures (RR 1.3 (1.0-1.5, p = .02)), and 'need for hospitalization' (i.e. intravenous antibiotics and/or bronchoscopy) (RR 1.4 (1.0-1.9, p = .03)). CR led to a significant increase in inhaled antibiotics only (RR 1.3 (1.0-1.6, p = .04)). CT but not CR, at routine biennial follow-up was associated with several changes in treatment and/or diagnostic testing, including the need for hospitalization.
Publisher: Wiley
Date: 05-08-2022
DOI: 10.1111/JPC.15665
Abstract: To determine the frequency of protracted bacterial bronchitis (PBB) in children referred to tertiary care with chronic cough and describe management prior to referral. A retrospective cohort study of all new patients with a history of ≥4 weeks of cough seen at the only tertiary paediatric outpatient respiratory service in Western Australia between July 2018 and June 2019. Medical records were reviewed until a final diagnosis was documented or otherwise for a period of 18 months. PBB was the most common cause and comprised 37.9% of all children referred to tertiary respiratory care with chronic cough. In children with PBB, the median cough duration at the time of first specialist review was 5.1 months (IQR 2.1–12.0 months). The most common referral source of PBB was primary practice (40.9%) and the most common working diagnosis pre‐referral was asthma (15.9%). Seventy‐eight percent of children with PBB had an ongoing cough at their first respiratory review, and of these, only 13.5% had been prescribed 4 weeks of antibiotics prior to their respiratory review. Asthma treatment had been prescribed for 34.0% of children with PBB. PBB is the most common cause of chronic cough in children referred to tertiary respiratory care and is frequently misdiagnosed and undertreated pre‐referral. There is a need to facilitate diagnosis and optimal management of PBB in primary care, which could result in earlier symptom resolution and potentially limit disease progression to bronchiectasis.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2017
Publisher: BMJ
Date: 07-2021
DOI: 10.1136/BMJRESP-2021-000956
Abstract: Despite advances in cystic fibrosis (CF) management and survival, the optimal treatment of pulmonary exacerbations remains unclear. Understanding the variability in treatment approaches among physicians might help prioritise clinical uncertainties to address through clinical trials. Physicians from Australia and New Zealand who care for people with CF were invited to participate in a web survey of treatment preferences for CF pulmonary exacerbations. Six typical clinical scenarios were presented three to paediatric and another three to adult physicians. For each scenario, physicians were asked to choose treatment options and provide reasons for their choices. Forty-nine CF physicians (31 paediatric and 18 adult medicine) participated more than half reported 10+ years of experience. There was considerable variation in primary antibiotic selection none was preferred by more than half of respondents in any scenario. For secondary antibiotic therapy, respondents consistently preferred intravenous tobramycin and a third antibiotic was rarely prescribed, except in one scenario describing an adult patient. Hypertonic saline nebulisation and twice daily chest physiotherapy was preferred in most scenarios while dornase alfa use was more variable. Most CF physicians ( %) preferred to change therapy if there was no early response. Professional opinion was the most common reason for antibiotic choice. Variation exists among CF physicians in their preferred choice of primary antibiotic and use of dornase alfa. These preferences are driven by professional opinion, possibly reflecting a lack of evidence to base policy recommendations. Evidence from high-quality clinical trials is needed to inform physician decision making.
Publisher: BMJ
Date: 09-2022
DOI: 10.1136/BMJOPEN-2021-056528
Abstract: Pulmonary exacerbations are associated with increased morbidity and mortality in people with cystic fibrosis (CF). There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations or how these outcomes should be measured. Outcomes of importance to people with lived experience of the disease are frequently omitted or inconsistently reported in studies, which limits the value of such studies for informing practice and policy. To better standardise outcome reporting and measurement, we aim to develop a core outcome set for studies of pulmonary exacerbations in people with CF (COS-PEX) and consensus recommendations for measurement of core outcomes. Preliminary work for development of COS-PEX has been reported, including (1) systematic reviews of outcomes and methods for measurement reported in existing studies of pulmonary exacerbations (2) workshops with people affected by CF within Australia and (3) a Bayesian knowledge expert elicitation workshop with health professionals to ascertain outcomes of importance. Here we describe a protocol for the additional stages required for COS-PEX development and consensus methods for measurement of core outcomes. These include (1) an international two-round online Delphi survey and (2) consensus workshops to review and endorse the proposed COS-PEX and to agree with methods for measurement. National mutual ethics scheme approval has been provided by the Child and Adolescent Health Service Human Research Ethics Committee (RGS 4926). Results will be disseminated via consumer and research networks and peer-reviewed publications. This study is registered with the Core Outcome Measures in Effectiveness Trials database.
Publisher: Wiley
Date: 24-09-2008
Publisher: Elsevier BV
Date: 10-2021
Publisher: Wiley
Date: 09-06-2022
DOI: 10.1111/ANS.17844
Abstract: Lung abscess is a rare condition in paediatrics with a paucity of literature. Intravenous antibiotics is the main therapy however interventional radiological approaches have led to the use of percutaneous drainage. Surgery is reserved for the management of complications. The aim of this study was to describe lung abscess in a cohort of paediatric patients' and determine associations between factors at presentation and outcomes. A 14‐year retrospective cohort study was conducted including all children who presented to a tertiary paediatric hospital in Western Australia with lung abscess. Clinical characteristics, laboratory and radiologic findings, management options and clinical outcomes were examined. Sixty‐eight patients (median age 3.6 (0.08–17.6) years 44.1% female) were identified to have a lung abscess, with 81% being primary lung abscess. Staphylococcus aureus (including MRSA ) and Streptococcus pneumoniae were the most common organisms identified, with S. aureus being most common in Aboriginal patients (80%). A total of 25 antibiotics were prescribed on initiation of treatment in over 20 combinations. 44.9% of patients had complications and hospitalization was prolonged. Patients with S. aureus had longer hospitalization (20.5 days (3–67) than those without (median 13 days (3–52), p = 0.04). There were no associations between factors at presentation and subsequent outcomes. Factors at presentation were not associated with outcomes. There is unwarranted variation in management of paediatric lung abscess and high complication rates. There is a need for collaboration and clinical practice guidelines to standardize care for lung abscess in children.
Publisher: Elsevier BV
Date: 12-2020
Publisher: European Respiratory Society (ERS)
Date: 04-2009
Publisher: European Respiratory Society (ERS)
Date: 04-2018
Publisher: Informa UK Limited
Date: 14-10-2016
DOI: 10.1080/02699052.2016.1201592
Abstract: Providing appropriate rehabilitation services for Acquired Brain Injury (ABI) in childhood presents a number of challenges for caregivers, health and education professionals and the young person as they develop. To record the challenges and possible creative solutions generated by an international group of professionals to address the needs of children with ABI. Review of information: Recommendations were generated from children's special interest group meetings of the International Brain Injury Association (Turin, Italy, 2001 Stockholm, Sweden, 2003 Melbourne, Australia, 2005 Lisbon, Portugal, 2008) and through meetings of the International Paediatric Brain Injury Society (IPBIS), formed in 2009. Delegates participating in the workshops were representative of nations from around the world and included The Netherlands, New Zealand, Australia, the UK, Finland, Germany, South Africa, the US, Canada, Sweden, Brazil and Italy. The information presented is based on a retrospective review of those meetings and the summaries of the topics considered.
Publisher: Springer Science and Business Media LLC
Date: 17-03-2022
DOI: 10.1186/S12890-022-01878-3
Abstract: First Nations children hospitalised with acute lower respiratory infections (ALRIs) are at increased risk of future bronchiectasis (up to 15–19%) within 24-months post-hospitalisation. An identified predictive factor is persistent wet cough a month after hospitalisation and this is likely related to protracted bacterial bronchitis which can progress to bronchiectasis, if untreated. Thus, screening for, and optimally managing, persistent wet cough one-month post-hospitalisation potentially prevents bronchiectasis in First Nations’ children. Our study aims to improve the post-hospitalisation medical follow-up for First Nations children hospitalised with ALRIs and thus lead to improved respiratory health. We hypothesize that implementation of a strategy, conducted in a culturally secure manner, that is informed by barriers and facilitators identified by both parents and health care providers, will improve medical follow-up and management of First Nations children hospitalized with ALRIs. Our trial is a multi-centre, pseudo-randomized stepped wedge design where the implementation of the strategy is tailored for each study site through a combined Participatory Action Research and implementation science approach informed by the Consolidated Framework of Implementation Research. Outcome measures will consist of three categories related to (i) health, (ii) economics and (iii) implementation. The primary outcome measure will be Cough-specific Quality of Life (PC-QoL). Outcomes will be measures at each study site/cluster in three different stages i.e., (i) nil-intervention control group, (ii) health information only control group and (iii) post-intervention group. If our hypothesis is correct, our study findings will translate to improved health outcomes (cough related quality of life) in children who have persistent wet cough a month after hospitalization for an ALRI. Trial registration ACTRN12622000224729, prospectively registered 8 February 2022, URL: www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382886& isReview=true .
Publisher: Springer Science and Business Media LLC
Date: 11-04-2021
Publisher: American Thoracic Society
Date: 15-03-2018
Publisher: Wiley
Date: 17-07-2018
DOI: 10.1113/JP276145
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.PRRV.2019.06.002
Abstract: Clinicians and other decision makers in healthcare use results from clinical trials to inform practice. Interpretation of clinical trial results can be challenging, as weaknesses in trial design, data collection, analysis or reporting, can compromise the usefulness of results. A good working knowledge of clinical trial design is essential to expertly interpret and determine the validity and generalizability of the results. This manuscript will give a brief overview of clinical trial design including the strengths and limitations of various approaches. The focus will be on confirmatory clinical trials.
Publisher: American Thoracic Society
Date: 09-2021
Publisher: Wiley
Date: 30-11-0002
DOI: 10.1002/PPUL.23636
Abstract: Induced sputum s ling holds promise as a method for obtaining s les representative of the lower airways in young children. Collection of induced sputum s les in young children differs from older children and adults' as pharyngeal suctioning is often required. Our aim was to determine the sensitivity and specificity of induced sputum with and without airway clearance techniques to detect lower airway pathogens in children less than age 7 with cystic fibrosis. Microbiological culture results were compared between 61 paired induced sputum and bronchoalveolar lavage fluid s les from young children with cystic fibrosis. The first cohort received no airway clearance and the second cohort received airway clearance. Induced sputum was s led within 7 days of bronchoscopy. Median age (range) of participants was 3.3 years (0.9-6.7). Sensitivity and specificity (95%CI) of induced sputum was 36.8% (16.3, 61.6), and 69% (52.9, 82.4), respectively (N = 61). In subgroup analysis, induced sputum with (N = 31) and without airway clearance (N = 30) demonstrated sensitivity of 50% (15.7, 84.3) and 27.3% (6.0, 61.0), respectively, and specificity of 60.9% (38.5, 80.3), and 78.9% (54.4, 93.9), respectively. Induced sputum is not highly sensitive or specific as routine surveillance for detection of lower airway pathogens in young children with cystic fibrosis. Pediatr Pulmonol. 2017 :182-189. © 2016 Wiley Periodicals, Inc.
Publisher: National Institute for Health and Care Research
Date: 03-2017
DOI: 10.3310/PHR05010
Abstract: Adolescent men have a vital yet neglected role in reducing unintended teenage pregnancy (UTP). There is a need for gender-sensitive educational interventions. To determine the value and feasibility of conducting an effectiveness trial of the If I Were Jack Relationship and Sexuality Education (RSE) intervention in a convenience quota s le of post-primary schools in Northern Ireland. Secondary objectives were to assess acceptability to schools, pupils (male/female, aged 14–15 years) and parents/guardians to identify optimal delivery structures and systems to establish participation rates and reach, including equality of engagement of different socioeconomic and religious types to assess trial recruitment and retention rates to assess variation in normal RSE practice to refine survey instruments to assess differences in outcomes for male and female pupils to identify potential effect sizes that might be detected in an effectiveness trial and estimate appropriate s le size for that trial and to identify costs of delivery and pilot methods for assessing cost-effectiveness. Cluster randomised Phase II feasibility trial with an embedded process and economic evaluation. A teacher-delivered classroom-based RSE resource – an interactive video drama (IVD) with classroom materials, teacher training and an information session for parents – to immerse young people in a hypothetical scenario of Jack, a teenager whose girlfriend is unintentionally pregnant. It addresses gender inequalities in RSE by focusing on young men and is designed to increase intentions to avoid UTP by encouraging young people to delay sexual intercourse and to use contraception consistently in sexual relationships. Abstinence from sexual intercourse (delaying initiation of sex or returning to abstinence) or avoidance of unprotected sexual intercourse (consistent correct use of contraception). Secondary outcomes included Knowledge, Attitudes, Skills and Intentions. The intervention proved acceptable to schools, pupils and parents, as evidenced through positive process evaluation. One minor refinement to the parental component was required, namely the replacement of the teacher-led face-to-face information session for parents by online videos designed to deliver the intervention to parents/guardians into their home. School recruitment was successful (target 25%, achieved 38%). No school dropped out. Pupil retention was successful (target 85%, achieved 93%). The between-group difference in incidence of unprotected sex of 1.3% (95% confidence interval 0.55% to 2.2%) by 9 months demonstrated an effect size consistent with those reported to have had meaningful impact on UTP rates (resulting in an achievable s le size of 66 schools at Phase III). Survey instruments showed high acceptability and reliability of measures (Cronbach’s alpha: 0.5–0.7). Economic evaluation at Phase III is feasible because it was possible to (1) identify costs of delivering If I Were Jack (mean cost per pupil, including training of teachers, was calculated as £13.66) and (2) develop a framework for assessing cost-effectiveness. Trial methods were appropriate, and recruitment and retention of schools and pupils was satisfactory, successfully demonstrating all criteria for progression to a main trial. The perceived value of culture- and gender-sensitive public health interventions has been highlighted. Progression to a Phase III effectiveness trial. Current Controlled Trials ISRCTN99459996. This project was funded by the NIHR Public Health Research programme and will be published in full in Public Health Research Vol. 5, No. 1. See the NIHR Journals Library website for further project information.
Publisher: Wiley
Date: 04-11-2016
DOI: 10.1002/PPUL.23638
Abstract: Ciprofloxacin (CIP) is frequently used when treating cystic fibrose (CF) patients with intermittent Pseudomonas aeruginosa (P. aeruginosa) lung colonization. However, approximately 20% of the patients progress to chronic infection despite early intervention. The aim of this study, was to investigate the pharmacokinetics of CIP, to evaluate if CYP3A4-related metabolism is involved and to find the optimal dose needed to eradicate intermittently colonizing bacteria in the lungs of CF patients. Methods An open-label, prospective pharmacokinetic study was performed. Twenty-two adult CF-patients were each given 500 mg CIP orally. One blood s le was taken at t = 0, and the following 12 hr, nine blood s les were collected. The optimal dose and interval was then calculated by Monte Carlo simulation. CYP3A4-activity was mesured using the Erythromycin Breath Test (ERMBT). Results A 14-fold variation in AUC for the 500 mg CIP (median 473.5 µg/ml × min), and a 30-fold variation in Cmax for CIP (median 2 µg/ml) was found. For CYP3A4-activity the variation was 8-fold. No correlation was found between the CYP3A4-activity and CIP-concentrations. The probability of eradicating intermittent P. aeruginosa colonization in the lungs of CF patients was found to be 57% (3 doses/day), when 500 mg CIP was given. It was calculated to be 89% (2 doses/day) and 94% (3 doses/day), respectivly if 750 mg CIP had been given. Conclusion A large pharmacokinetic difference of CIP in CF patiens was found, not explained by CYP3A4 variation. CIP should be given at 750 mg two or three times daily to adult CF patients with intermittently colonization. Pediatr Pulmonol. 2017 :319-323. © 2016 Wiley Periodicals, Inc.
Publisher: Research Square Platform LLC
Date: 23-09-2022
DOI: 10.21203/RS.3.RS-2079022/V1
Abstract: Survival statistics, estimated using data from national cystic fibrosis (CF) registries, inform the CF community and monitor disease progression. This study aimed to estimate survival among people with CF in Australia and to identify factors associated with survival. This population-based cohort study used prospectively collected data from 23 Australian CF centres participating in the Australian CF Data Registry (ACFDR) from 2005-2020. Period survival analysis was used to calculate median age of survival estimates for each 5-year window from 2005-2009 until 2016-2020. The overall median survival was estimated using the Kaplan-Meier method. Between 2005-2020 the ACFDR followed 4,601 people with CF, noting 516 (11.2%) deaths including 195 following lung transplantation. Out of the total s le, more than half (52.5%) were male and 395 (8.6%) had undergone lung transplantation. Two thirds of people with CF (66.1%) were diagnosed before six weeks of age or by newborn renatal screening. The overall median age of survival was estimated as 54.0 years (95% CI: 51.0–57.04). Estimated median survival increased from 48.9 years (95% CI: 44.7–53.5) for people with CF born in 2005-2009, to 56.3 years (95% CI: 51.2–60.4) for those born in 2016-2020. Factors independently associated with reduced survival include being F508del homozygous, receiving a lung transplant, having low FEV1pp and BMI. Median survival estimates are increasing in CF in Australia. This likely reflects multiple factors, including newborn screening, improvement in diagnosis, refinements in CF management and centre-based multidisciplinary care.
Publisher: Frontiers Media SA
Date: 16-09-2022
DOI: 10.3389/FPED.2022.1010016
Abstract: Bronchiectasis (not related to cystic fibrosis) is a chronic lung disease caused by a range of etiologies but characterized by abnormal airway dilatation, recurrent respiratory symptoms, impaired quality of life and reduced life expectancy. Patients typically experience episodes of chronic wet cough and recurrent pulmonary exacerbations requiring hospitalization. Early diagnosis and management of childhood bronchiectasis are essential to prevent respiratory decline, optimize quality of life, minimize pulmonary exacerbations, and potentially reverse bronchial disease. Disease monitoring potentially allows for (1) the early detection of acute exacerbations, facilitating timely intervention, (2) tracking the rate of disease progression for prognostic purposes, and (3) quantifying the response to therapies. This narrative review article will discuss methods for monitoring disease progression in children with bronchiectasis, including lung imaging, respiratory function, patient-reported outcomes, respiratory exacerbations, sputum biomarkers, and nutritional outcomes.
Publisher: Wiley
Date: 10-02-2017
DOI: 10.1111/JPC.13458
Abstract: Patient adherence is integral to the effectiveness of prescribed treatment, and is associated with beneficial disease outcomes, yet in adolescents with cystic fibrosis, adherence is often sub-optimal. Multiple factors may contribute to treatment adherence, including disease knowledge and self-efficacy. In adolescents with cystic fibrosis: (i) to compare the disease knowledge of adolescents and their parents before transition to adult care (ii) to determine the relationship between disease knowledge (adolescent, parent) and adherence and (iii) to evaluate self-efficacy and its association with disease knowledge and adherence. Adolescents with cystic fibrosis and their parents were recruited from a tertiary children's hospital. Disease knowledge and self-efficacy was assessed using the Knowledge of Disease Management-CF and General Self-Efficacy Scales respectively. Using pharmacy records, medication possession ratio was calculated to measure treatment adherence in the preceding year. Thirty-nine adolescent (aged 12-17 (median 14) years) and parent pairs were recruited. Adherence to hypertonic saline, but not other medications, was significantly associated with disease knowledge in adolescents (r Disease knowledge is sub-optimal in adolescents with cystic fibrosis, even in the 2 years immediately before transition to adult care. Given that adherence with some treatments has been associated with disease knowledge our results suggest the need for educational interventions in adolescents with cystic fibrosis to optimise self-management and health outcomes.
Publisher: BMJ
Date: 13-09-2018
Publisher: Wiley
Date: 15-11-2018
DOI: 10.1111/JPC.14305
Abstract: Chronic respiratory disease is common among Aboriginal Australians. Chronic wet cough is an early marker of chronic disease in children but often goes undetected due, in part, to delayed health seeking by families. Currently, no studies have examined the reasons for delayed health seeking for children's chronic cough. To identify the barriers to, and enablers for, seeking medical help for chronic wet cough in Aboriginal children. This was a qualitative study, gathering data through in idual semi-structured, in-depth interviews and focus groups to ascertain Aboriginal family knowledge, attitudes and beliefs about seeking health care for chronic wet cough in children in a regional Kimberley town, Western Australia between October 2017 and March 2018. Forty Aboriginal community members participated. The three key barriers identified were: 'Cough normalisation', that is, 70% of participants considered chronic cough normal (with 53% of participants' previous interactions with doctors informing their understanding of chronic cough) the lack of health literacy information and a sense of disempowerment (belief that no medical action would be taken and inability to challenge doctors). The key expressed enablers were provision of health literacy information and health practitioner training to assess and treat chronic wet cough in children. All participants reported that they would seek help for chronic wet cough once they were informed that it could signify underlying disease. Results highlight the need for a culturally appropriate information and education to inform Aboriginal families and their health practitioners of the importance of chronic wet cough in children.
Publisher: BMJ
Date: 22-04-2021
Publisher: Wiley
Date: 03-08-2020
DOI: 10.1111/RESP.13661
Publisher: BMJ
Date: 08-2019
DOI: 10.1136/BMJOPEN-2019-030348
Abstract: Clinical decision-making is a complex process. Patient preference information regarding desirable health states should inform treatment and is critical to agreeing on goals of therapy. Cystic fibrosis (CF) is a common, inheritable multisystem disorder for which the major manifestation is progressive, chronic lung disease. Intermittent pulmonary exacerbations are a hallmark of disease and these drive lung damage that results in premature death. We suspect that clinicians make assumptions, most likely implicit assumptions, about outcomes that are desired by patients who are treated for pulmonary exacerbations. The aim of this study is to identify and quantify the preferences of patients with cystic fibrosis regarding treatment outcomes. We will develop a discrete choice experiment (DCE) in collaboration with people with CF and their carers, and evaluate how patients make trade-offs between different aspects of health-related status when considering treatment options. Ethics approval for all aspects of this study was granted by the Western Australia Child and Adolescent Health Service Human Research Ethics Committee [RGS903]. Weighted preference information from the DCE will be used to develop a multiattribute utility instrument as a measure of treatment success in the upcoming Bayesian Evidence-Adaptive Trial to optimise management of CF. Dissemination of results will also occur through peer-reviewed publications and presentations to relevant stakeholders and research networks.
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 09-09-2022
DOI: 10.1186/S13023-022-02508-1
Abstract: Children’s interstitial and diffuse lung disease (chILD) is a complex heterogeneous group of lung disorders. Gene panel approaches have a reported diagnostic yield of ~ 12%. No data currently exist using trio exome sequencing as the standard diagnostic modality. We assessed the diagnostic utility of using trio exome sequencing in chILD. We prospectively enrolled children meeting specified clinical criteria between 2016 and 2020 from 16 Australian hospitals. Exome sequencing was performed with analysis of an initial gene panel followed by trio exome analysis. A subset of critically ill infants underwent ultra-rapid trio exome sequencing as first-line test. 36 patients [median (range) age 0.34 years (0.02–11.46) 11F] were recruited from multiple States and Territories. Five patients had clinically significant likely pathogenic athogenic variants ( RARB, RPL15, CTCF, RFXANK, TBX4 ) and one patient had a variant of uncertain significance ( VIP ) suspected to contribute to their clinical phenotype, with VIP being a novel gene candidate. Trio exomes (6/36 16.7%) had a better diagnostic rate than gene panel (1/36 2.8%), due to the ability to consider a broader range of underlying conditions. However, the aetiology of chILD in most cases remained undetermined, likely reflecting the interplay between low penetrant genetic and environmental factors.
Publisher: BMJ
Date: 25-10-2012
DOI: 10.1136/ARCHDISCHILD-2012-302312
Abstract: Adherence to prescribed inhaled medication is often low in young children. Poor adherence to medication may contribute to lack of symptom control. Doctors are not good at predicting the adherence rates of their patients, and parental report of adherence does not correlate with objective measures of adherence. The objective of this study was to investigate whether parental admission of non-adherence and reasons given for non-adherence correlated with objectively measured adherence. Adherence to prescribed inhaled corticosteroid treatment was monitored electronically in 132 children aged 2–6 years who were participating in a randomised controlled trial comparing different inhaler devices. Follow-up was carried out every 3 months for a year. Parental answers to simple questions about adherence were compared to electronically measured adherence. Mean adherence ranged from zero to 100%. Intra-participant adherence varied throughout the year-long study period (mean variance for in idual children between quarterly periods was 28.5%). Parents who reported missed doses, generally missed at least half of the prescribed doses. Parents who reported that not a single prescribed dose was missed, still missed 20% of doses on average. Adherence was particularly low when parents cited initiating their own trial off medication as a reason for missing doses. By examining parental response to questions enquiring whether any doses were missed, healthcare providers can gain a modest degree of insight into their patients’ true adherence to prescribed medication. Adherence to prescribed asthma medication is extremely variable in young children. Data from this study were derived from a randomised controlled trial (ACTRN12608000294358).
Publisher: Wiley
Date: 17-06-2012
DOI: 10.1111/J.1440-1754.2011.02123.X
Abstract: Wheeze in childhood may comprise different underlying diseases. Disease-specific treatment could potentially improve treatment efficacy. Various attempts have been made to differentiate between pre-school wheeze phenotypes. In this review, the results of clinical trials evaluating treatment of pre-school wheeze are discussed, with specific emphasis on the characteristics and phenotype of the study populations. Evidence suggests that systemic corticosteroids are not beneficial for the treatment of mild-to-moderate exacerbations of pre-school wheeze, irrespective of phenotype. The use of high-dose intermittent inhaled corticosteroid treatment cannot be recommended because of unacceptable side effects. Treatment with regular inhaled corticosteroids and leukotriene antagonists offer modest benefit, but neither treatment reduces hospitalisation rates. There is currently some evidence for a phenotype-specific effect of treatment. Phenotype-directed treatment of pre-school wheeze is currently limited by our ability to accurately differentiate between clinically useful phenotypes.
Publisher: European Respiratory Society (ERS)
Date: 20-04-2018
DOI: 10.1183/13993003.00238-2018
Abstract: In children with cystic fibrosis (CF) the associations between oropharyngeal swabs (OPSs) for detection of Pseudomonas and lung disease have not been evaluated. OPS and bronchoalveolar lavage (BAL) s les were obtained annually in children with CF from 2005 to 2017. OPS test characteristics were calculated using BAL as “gold standard”. Results were related to lung inflammation (BAL neutrophil elastase and interleukin-8), structural lung disease (chest computed tomography PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) scores), respiratory exacerbations and future detection of Pseudomonas on BAL. From 181 patients, 690 paired OPS–BAL cultures were obtained. Prevalence of Pseudomonas in BAL was 7.4%. OPS sensitivity was 23.0% and specificity was 91.4%, reducing the post-test probability for a positive BAL following a negative OPS to 6.3%. Pseudomonas on OPS was not associated with lung inflammation or respiratory exacerbations, but was weakly associated with current PRAGMA-CF %Disease score (p=0.043). Pseudomonas on BAL was associated with positive neutrophil elastase (OR 4.17, 95% CI 2.04–8.53 p .001), increased interleukin-8 (p .001), increased all baseline PRAGMA computed tomography scores (p .001), progression of PRAGMA computed tomography scores (p .05) and increased risk of respiratory exacerbations (incidence rate ratio 2.11, 95% CI 1.15–3.87 p=0.017). In children with CF OPSs only marginally change the probability of detecting lower airway Pseudomonas and are not associated with lung disease indices nor exacerbations risk.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2022
DOI: 10.1038/S41598-022-24374-4
Abstract: Survival statistics, estimated using data from national cystic fibrosis (CF) registries, inform the CF community and monitor disease progression. This study aimed to estimate survival among people with CF in Australia and to identify factors associated with survival. This population-based cohort study used prospectively collected data from 23 Australian CF centres participating in the Australian CF Data Registry (ACFDR) from 2005–2020. Period survival analysis was used to calculate median age of survival estimates for each 5-year window from 2005–2009 until 2016–2020. The overall median survival was estimated using the Kaplan–Meier method. Between 2005–2020 the ACFDR followed 4,601 people with CF, noting 516 (11.2%) deaths including 195 following lung transplantation. Out of the total s le, more than half (52.5%) were male and 395 (8.6%) had undergone lung transplantation. Two thirds of people with CF (66.1%) were diagnosed before six weeks of age or by newborn renatal screening. The overall median age of survival was estimated as 54.0 years (95% CI: 51.0–57.04). Estimated median survival increased from 48.9 years (95% CI: 44.7–53.5) for people with CF born in 2005–2009, to 56.3 years (95% CI: 51.2–60.4) for those born in 2016–2020. Factors independently associated with reduced survival include receiving a lung transplant, having low FEV 1 pp and BMI. Median survival estimates are increasing in CF in Australia. This likely reflects multiple factors, including newborn screening, improvement in diagnosis, refinements in CF management and centre-based multidisciplinary care.
Publisher: Wiley
Date: 18-10-2020
DOI: 10.1111/PAN.14028
Publisher: Elsevier BV
Date: 11-2020
Publisher: Springer Science and Business Media LLC
Date: 14-12-2021
Publisher: Frontiers Media SA
Date: 21-02-2022
Abstract: ATP Binding Cassette Subfamily A Member 3 (ABCA-3) is a lipid transporter protein highly expressed in type-II alveolar (AT-II) cells. Mutations in ABCA3 can result in severe respiratory disease in infants and children. To study ABCA-3 deficiency in vitro , primary AT-II cells would be the cell culture of choice although s le accessibility is limited. Our aim was to investigate the suitability of primary nasal epithelial cells, as a surrogate culture model for AT-II cells, to study ABCA-3 deficiency. Expression of ABCA3 , and surfactant protein genes, SFTPB and SFTPC , was detected in primary nasal epithelial cells but at a significantly lower level than in AT-II cells. ABCA-3, SP-B, and SP-C were detected by immunofluorescence microscopy in primary nasal epithelial cells. However, SP-B and SP-C were undetectable in primary nasal epithelial cells using western blotting. Structurally imperfect lamellar bodies were observed in primary nasal epithelial cells using transmission electron microscopy. Functional assessment of the ABCA-3 protein demonstrated that higher concentrations of doxorubicin reduced cell viability in ABCA-3 deficient nasal epithelial cells compared to controls in an assay-dependent manner. Our results indicate that there may be a role for primary nasal epithelial cell cultures to model ABCA-3 deficiency in vitro , although additional cell culture models that more effectively recapitulate the AT-II phenotype may be required.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.JCF.2019.12.011
Abstract: Young people with cystic fibrosis (CF) may be at increased risk of social isolation and mental illness. This study aimed to design and evaluate the usability and acceptability of a smartphone application (app) to support the social connectedness and wellbeing of young people living with CF. Young people with CF aged 12-17 years (N = 22) were recruited from two paediatric hospitals in Australia. Study participants tested the CF app for six weeks before responding to an online survey about the app's usability and acceptability. A subs le of participants (n = 20) discussed the app's strengths and weaknesses during 11 online group interviews. During the six-week testing period, 77% of participants used the app at least once a week and 82% accessed the app from a smartphone. Usability of the CF app was rated high. Most participants agreed the app was easy to use (86%) and felt comfortable using it (96%). Acceptability of the app was moderate. 77% of participants agreed they would recommend the app to others. Recommendations to improve the app's functionality and acceptability included locating the chatroom within the app rather than redirecting users to a web browser and allowing users to personalise images, wellness tips and videos. This study developed and tested a highly usable, and moderately acceptable, smartphone app to improve the psychosocial health of young people living with CF. Future research will test the efficacy of the CF app on users' social connectedness and wellbeing.
Publisher: American Thoracic Society
Date: 09-2019
Publisher: Elsevier BV
Date: 10-2021
Publisher: American Thoracic Society
Date: 15-03-2020
Publisher: Elsevier BV
Date: 03-2021
No related grants have been discovered for Juan A Rodriguez-Aguilar.