ORCID Profile
0000-0002-1963-5415
Current Organisation
UNSW Sydney
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Publisher: Wiley
Date: 06-2020
DOI: 10.1111/RESP.13777
Publisher: Elsevier BV
Date: 05-2019
Publisher: Wiley
Date: 08-02-2013
DOI: 10.1002/PPUL.22776
Abstract: Exhaled breath condensate (EBC) analysis is a simple non-invasive technique that allows repeated collection of breath s les with a minimum of inconvenience for the subject. These breath s les can potentially indicate lung disease activity and given the ease of collection, EBC is becoming a useful research tool in the study of respiratory diseases. It has the potential to be used in both population-based studies and in the context of pediatric asthma it may prove useful in diagnosis and monitoring. A systematic review was conducted to identify studies of EBC markers in childhood asthma. Most of the studies were cross-sectional in design, and the results suggest that simple chemical entities such as hydrogen ions (as pH), hydrogen peroxide, and oxides of nitrogen are associated with pediatric allergic asthma and exacerbations. In addition, more complex molecules including leukotrienes, prostaglandins, and cytokines such as the interleukins IL-4 and IL-5 are also elevated in the breath of those with asthma. EBC has the potential to aid diagnosis, and to evaluate the inflammatory status of asthmatic children. Future studies may be able to refine further how best to collect EBC s les, to interpret them, and the technique has the potential to allow repeated s ling which will allow studies of natural history, pathogenesis and response to treatment to be undertaken.
Publisher: Wiley
Date: 2001
DOI: 10.1002/1099-0496(200102)31:2<106::AID-PPUL1017>3.0.CO;2-M
Publisher: European Respiratory Society
Date: 09-2017
Publisher: BMJ
Date: 10-2008
Abstract: The incidence of empyema in children is increasing worldwide. While there are emerging data for the best treatment options, there is little evidence to support the imaging modalities used to guide treatment, particularly with regard to the role of routine CT scanning. The aims of this study were to develop a radiological scoring system for paediatric empyema and to assess the utility of routine CT scanning in this disease. Children with empyema were prospectively enrolled over a 3-year period into a randomised clinical trial of video-assisted thoracoscopic surgery versus percutaneous chest drain insertion and urokinase. All children received a preoperative chest radiograph (CXR), pleural ultrasound scan (USS) and chest CT scan. In the urokinase arm the clinician inserted the drain with USS evidence only and did not have access to the CT scan at the time of insertion to reflect clinical practice. A scoring system was developed for each in idual radiological modality and used to compare imaging characteristics of the pleural fluid collection and underlying parenchyma and to assess the utility of USS and CT to predict length of stay after the intervention. Of the 60 subjects recruited, 46 had USS images available for review, 36 had a CT scan which met the inclusion criteria and 31 had all three radiological measurements (CT, USS and CXR) available for analysis. There was substantial interobserver agreement for USS grades (kappa = 0.709) and moderate agreement for total CT scores (kappa = 0.520). There were weak correlations between USS grade and total CT score as well as CT loculation and density scores. Of the 25 CXRs showing simple opacification of the underlying parenchyma only, CT demonstrated simple consolidation (n = 14), necrotising pneumonia (n = 7), cavitary necrosis (n = 3) and pneumatoceles (n = 1). No abnormality was detected on CT scanning which directly altered clinical management. Neither the USS score nor the CT score, nor a combination of the two, were able to predict length of hospital stay. CT scanning detects more parenchymal abnormalities than chest radiography. However, the additional information does not alter management and is unable to predict clinical outcome. This suggests that there is no role for the routine use of CT scanning in children if treated with urokinase and percutaneous chest drain. The omission of routine CT scanning in empyema will reduce the exposure of children to unnecessary radiation and reduce costs. The trial is fully registered with clinicaltrials.gov (ID: NCT00144950).
Publisher: Elsevier BV
Date: 06-2010
Publisher: Elsevier BV
Date: 09-2003
Publisher: Wiley
Date: 06-2020
DOI: 10.1111/RESP.13778
Publisher: Wiley
Date: 30-04-2015
DOI: 10.1002/PPUL.23183
Abstract: Childhood interstitial lung disease (chILD) is a group of rare chronic and complex disorders of variable pathology. There has been no systematic review of published chILD research. This study aimed to describe chILD classification systems, epidemiology, morbidity, treatments, outcomes, and the impact of chILD on families and the burden on health services. A systematic literature search for original studies on chILD was undertaken in the major biomedical databases to the end of December 2013. Epidemiological studies, case series and studies describing classification systems were included. Single case studies were excluded. The search yielded 37 publications that met study criteria. Four different chILD classification systems have been proposed in the past decade. The incidence of chILD has been estimated at 0.13-16.2 cases/100,000 children/year. One to five new cases presented to in idual hospitals each year. In developed countries, the median mortality was 13% (6-19%). Morbidity and outcomes were highly variable and not systematically reported. Corticosteroids and hydroxychloroquine were the most common treatments. The impact of chILD on families and the burden on health services has not been studied. The heterogeneity of the chILD group of disorders, different determinations of what constitutes a chILD disorder and, a paucity of large epidemiological studies precludes consolidation of results across studies. Consensus on chILD classification is needed to support diagnosis and allow direct comparisons of research evidence. Active disease surveillance and international patient registries are required to advance understanding and management of chILD.
Publisher: BMJ
Date: 2005
Publisher: MyJove Corporation
Date: 10-11-2021
DOI: 10.3791/63090
Publisher: Wiley
Date: 09-2009
DOI: 10.1111/J.1440-1843.2009.01595.X
Abstract: Human research ethics committees provide essential review of research projects to ensure the ethical conduct of human research. Several recent reports have highlighted a complex process for successful application for human research ethics committee approval, particularly for multi-centre studies. Limited resources are available for the execution of human clinical research in Australia and around the world. This report overviews the process of ethics approval for a National Health and Medical Research Council-funded multi-centre study in Australia, focussing on the time and resource implications of such applications in 2007 and 2008. Applications were submitted to 16 hospital and two university human research ethics committees. The total time to gain final approval from each committee ranged between 13 and 77 days (median = 46 days) the entire process took 16 months to complete and the research officer's time was estimated to cost $A34 143. Obstacles to timely human research ethics committee approval are reviewed, including recent, planned and potential initiatives that could improve the ethics approval of multi-centre research.
Publisher: Elsevier BV
Date: 10-2022
Publisher: Public Library of Science (PLoS)
Date: 13-02-2017
Publisher: Elsevier BV
Date: 06-2017
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/IMJ.13528
Abstract: When registries collect accurate clinical data over time, they can act as fundamental support structures for patients and their families and powerful cost-effective instruments to support clinical trials and translational research to improve quality of care, quality of life and survival. Registries are critical for rare diseases (RD) with low prevalence and propensity for variation in treatment and outcomes. Rare Voices Australia is leading a call for action to the research and clinical community to prioritise RD data collection and develop an integrated RD Registry strategy for Australia. Financial, operational and governance challenges exist for establishing and maintaining RD registries. As a multidisciplinary team whose interests converge on RD, we highlight the need for the establishment of an Australian RD Registry Alliance. This 'umbrella' organisation will: (i) bring together existing RD registries across Australia (ii) establish National RD Registry Standards to support interoperability and cohesion across registries (iii) develop strategies to attract sustainable funding from government and other sources to maximise the utility of existing RD registries and support the development of new RD registries. The most important role for the Alliance would be to use the RD registries for translational research to address current knowledge gaps about RD and to improve the care for the over 1.4 million Australians estimated to live with RD.
Publisher: Future Medicine Ltd
Date: 08-2009
DOI: 10.2217/PHE.09.31
Abstract: Respiratory syncytial viral infections cause considerable childhood morbidity, and in some countries significant mortality, especially in infants with pre-existing conditions such as bronchopulmonary dysplasia and congenital heart disease. Currently, there is no active vaccine and attempts to prevent and ameliorate the effects of infection are focused on passive immunization by human monoclonal antibodies. This review focuses on the clinical sequelae of respiratory syncytial viral infections in high-risk patients and discusses the effects of public health measures and passive immunization on medical and socioeconomic outcomes.
Publisher: Wiley
Date: 17-07-2020
DOI: 10.1111/JPC.14560
Abstract: Acute otitis media (AOM) is the most common infectious disease for which antibiotics are prescribed its management is costly and has the potential to increase the antimicrobial resistance of this infection. This study measured the levels of adherence to the clinical practice guidelines (CPGs) of AOM and otitis media with effusion (OME) management in Australian children. We searched for national and international CPGs relating to AOM and OME in children and created 37 indicators for assessment. We reviewed medical records for adherence to these indicators in 120 locations, across one inpatient and three ambulatory health-care settings. Our review s le was obtained from three Australian states that contain 60% of the nation's children. We reviewed the records of 1063 children with one or more assessments of CPG adherence for otitis media. Of 22 indicators with sufficient data, estimated adherence ranged from 7.4 to 99.1%. Overuse of treatment, particularly overprescribing of antibiotics, was more common than underuse. A frequent lack of adherence with recommended care was observed for children aged between 1 and 2 years with AOM. Adherence varied by health-care setting, with emergency departments and inpatient settings more adherent to CPGs than general practices. Our assessment of a number of indicators in the common settings in which otitis media is treated found that guideline adherence varied widely between in idual indicators. Internationally agreed standards for diagnosis and treatment, coupled with clinician education on the existence and content of CPGs and clinical decision support, are needed to improve the management of children presenting with AOM and OME.
Publisher: Wiley
Date: 09-08-2020
DOI: 10.1111/DMCN.14640
Publisher: Wiley
Date: 10-2016
DOI: 10.1111/JPC.13356
Publisher: European Respiratory Society
Date: 04-09-2022
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JCF.2017.03.010
Abstract: Fecal calprotectin may be used as a non-invasive method to assess the effect of novel therapies on the gut in cystic fibrosis (CF). Stools from CF patients and healthy controls (HC) (0-10years old) were prospectively collected for evaluation of temporal trends. 130 CF s les (64 subjects) and 114 HC s les (101 subjects) were collected. Overall, fecal calprotectin levels were different in CF patients and HC from 0 to 10years (P=0.0002). Fecal calprotectin in CF was significantly lower than HC from 0 to 1years (P=0.03) and demonstrated an upward trajectory until 4years. From >4 to 10years calprotectin was consistently higher in CF patients compared with HC (P=0.007). Fecal calprotectin levels in children with CF and HC were age-dependent and had distinct trajectories. Careful interpretation of calprotectin is required if used in drug trials for CF, particularly in children less than 4years old.
Publisher: Informa UK Limited
Date: 10-2023
DOI: 10.2147/JAA.S421158
Publisher: American Thoracic Society
Date: 05-2010
DOI: 10.1164/AJRCCM-CONFERENCE.2010.181.1_MEETINGABSTRACTS.A3286
Publisher: Public Library of Science (PLoS)
Date: 22-05-2020
Publisher: Elsevier BV
Date: 12-2008
Publisher: American Diabetes Association
Date: 12-11-2010
DOI: 10.2337/DC09-1492
Abstract: Progressive β-cell loss causes catabolism in cystic fibrosis. Existing diagnostic criteria for diabetes were based on microvascular complications rather than on cystic fibrosis–specific outcomes. We aimed to relate glycemic status in cystic fibrosis to weight and lung function changes. We determined peak blood glucose (BGmax) during oral glucose tolerance tests (OGTTs) with s les every 30 min for 33 consecutive children (aged 10.2–18 years). Twenty-five also agreed to undergo continuous glucose monitoring (CGM) (Medtronic). Outcome measures were change in weight standard deviation score (wtSDS), percent forced expiratory volume in 1 s (%FEV1), and percent forced vital capacity (%FVC) in the year preceding the OGTT. Declining wtSDS and %FVC were associated with higher BGmax (both P = 0.02) and with CGM time & .8 mmol/l (P = 0.006 and P = 0.02, respectively) but not with BG120 min. A decline in %FEV1 was related to CGM time & .8 mmol/l (P = 0.02). Using receiver operating characteristic (ROC) analysis to determine optimal glycemic cutoffs, CGM time above 7.8 mmol/l ≥4.5% detected declining wtSDS with 89% sensitivity and 86% specificity (area under the ROC curve 0.89, P = 0.003). BGmax ≥8.2 mmol/l gave 87% sensitivity and 70% specificity (0.76, P = 0.02). BG120 min did not detect declining wtSDS (0.59, P = 0.41). After exclusion of two patients with BG120 min ≥11.1 mmol/l, the decline in wtSDS was worse if BGmax was ≥8.2 mmol/l (−0.3 ± 0.4 vs. 0.0 ± 0.4 for BGmax & .2 mmol/l, P = 0.04) or if CGM time above 7.8 mmol/l was ≥4.5% (−0.3 ± 0.4 vs. 0.1 ± 0.2 for time & .5%, P = 0.01). BGmax ≥8.2 mmol/l on an OGTT and CGM time above 7.8 mmol/l ≥4.5% are associated with declining wtSDS and lung function in the preceding 12 months.
Publisher: Wiley
Date: 2009
DOI: 10.1002/PPUL.20917
Abstract: Surgery for congenital and early childhood lung cysts is often dictated by symptoms such as respiratory distress, infection or pneumothorax. Asymptomatic cysts present a therapeutic dilemma: surgical intervention and "conservative" observation have advocates. The risk of malignancy in such cysts is considered by some an indication for surgical intervention and is reviewed in this paper. Pleuropulmonary blastoma (PPB) is the most frequent malignancy associated with childhood lung cysts. Although rare, PPB occurs predictably in certain clinical and familial situations. This unique biology of PPB can inform the cyst management decision. The earliest manifestation of PPB is a malignant lung cyst in young children, clinically and radiographically indistinguishable from benign congenital lung cysts. Histopathologic examination differentiates cystic PPB from the benign cystic variants. Surgical excision of cystic PPB (with or without chemotherapy) cures approximately 85-90% of children. If not excised, cystic PPB evolves to cystic/solid or solid high-grade sarcoma (cure rate 45-60%) by age 2-6 years. Numerous reports of "malignancy in a congenital lung cyst" are now understood as the characteristic progression of cystic PPB. PPB is genetically determined in many cases. Detailed family history may reveal the hallmarks of PPB in the patient or young relatives: a unique constellation of diseases including lung cysts, cystic nephroma, childhood cancers, stromal sex-chord ovarian tumors, seminomas or dysgerminomas, intestinal polyps, thyroid hyperplasias, and hamartomas. Pneumothorax and multifocal/bilateral lung cysts also characterize PPB. These diagnoses predict that a lung cyst is more likely PPB than a benign congenital cyst. Patients fitting this pattern deserve histologic diagnosis. The genetic basis for this heritable syndrome is unknown but is being actively investigated.
Publisher: European Respiratory Society (ERS)
Date: 10-2021
DOI: 10.1183/23120541.00448-2020
Abstract: Patient-oriented research approaches that reflect the needs and priorities of those most affected by health research outcomes improves translation of research findings into practice. Targeted therapies for cystic fibrosis (CF) are now a viable treatment option for some eligible in iduals despite the heterogeneous patient-specific therapeutic response. This has necessitated development of a clinical tool that predicts treatment response for in idual patients. Patient-derived mini-organs (organoids) have been at the forefront of this development. However, little is known about their acceptability in CF patients and members of the public. We used a cross-sectional observational design to conduct an online survey in people with CF, their carers and community comparisons. Acceptability was examined in five domains: 1) willingness to use organoids, 2) perceived advantages and disadvantages of organoids, 3) acceptable out-of-pocket costs, 4) turnaround time and 5) source of tissue. In total, 188 participants completed the questionnaire, including adults with CF and parents of children with CF (90 (48%)), and adults without CF and parents of children without CF (98 (52%)). Use of organoids to guide treatment decisions in CF was acceptable to 86 (95%) CF participants and 98 (100%) community participants. The most important advantage was that organoids may improve treatment selection, improving the patient's quality of life and life expectancy. The most important disadvantage was that the organoid recommended treatment might be unavailable or too expensive. These findings indicate acceptance of patient-derived organoids as a tool to predict treatment response by the majority of people surveyed. This may indicate successful future implementation into healthcare systems.
Publisher: Elsevier BV
Date: 08-2022
Publisher: BMJ
Date: 05-2007
Publisher: Elsevier BV
Date: 06-2003
Publisher: American Thoracic Society
Date: 05-2010
DOI: 10.1164/AJRCCM-CONFERENCE.2010.181.1_MEETINGABSTRACTS.A3277
Publisher: Cambridge University Press (CUP)
Date: 02-12-2015
DOI: 10.1017/S0950268815003015
Abstract: Linked administrative population data were used to estimate the burden of childhood respiratory syncytial virus (RSV) hospitalization in an Australian cohort aged years. RSV-coded hospitalizations data were extracted for all children aged years born in New South Wales (NSW), Australia between 2001 and 2010. Incidence was calculated as the total number of new episodes of RSV hospitalization ided by the child-years at risk. Mean cost per episode of RSV hospitalization was estimated using public hospital cost weights. The cohort comprised of 870 314 children. The population-based incidence/1000 child-years of RSV hospitalization for children aged years was 4·9 with a rate of 25·6 in children aged months. The incidence of RSV hospitalization (per 1000 child-years) was 11·0 for Indigenous children, 81·5 for children with bronchopulmonary dysplasia (BPD), 10·2 for preterm children with gestational age (GA) 32–36 weeks, 27·0 for children with GA 28–31 weeks, 39·0 for children with GA weeks and 6·7 for term children with low birthweight. RSV hospitalization was associated with an average annual cost of more than AUD 9 million in NSW. RSV was associated with a substantial burden of childhood hospitalization specifically in children aged months and in Indigenous children and children born preterm or with BPD.
Publisher: Elsevier BV
Date: 06-2018
Publisher: American Thoracic Society
Date: 05-2005
Publisher: Wiley
Date: 20-05-2016
DOI: 10.1111/JPC.13205
Abstract: Very premature infants consume healthcare resources following discharge from neonatal intensive care units (NICU). This study aimed to evaluate the burden of respiratory related rehospitalisation within the first 3 years post discharge in very premature infants in an Australian population. Rehospitalisation of a 4-year cohort of NICU survivors, born less than 32 weeks gestation, was derived from data linkage of three state-wide databases including NSW Neonatal Intensive Care Units' Data Collection, Admitted Patient Data Collection and the Death Registry. Rehospitalisation diagnoses were determined by ICD-10 AM codes. Of the 2939 survivors, 525 (18%) had bronchopulmonary dysplasia (BPD) and 261 BPD infants (50%) were discharged on home oxygen. Almost two-third (1860, 63%) of the survivors are required rehospitalisation, respiratory causes, including 394 respiratory syncytial virus (RSV)-related, accounted for 2668 (48%) of the 5599 rehospitalisations. Significantly more home oxygen BPD survivors had respiratory (70%) and RSV-related (22%) rehospitalisations than the BPD infants not needing home oxygen (58% and 18%, respectively), and the survivors without BPD had the lowest rates (32% and 10%, P < 0.001). Most respiratory (61%) and RSV-related (74%) rehospitalisations occurred during the first 12 months post discharge. No RSV-related fatality occurred. Amongst the total 17 562 hospital days, respiratory and RSV-related admissions accounted for 10 905 (62%) and 3031 (17.2%) days. In multivariable logistic analyses, home oxygen and maternal indigenous status were independently associated with high (3 or more) respiratory and RSV rehospitalisation rates. Respiratory rehospitalisations are common in very premature survivors. Home oxygen and indigenous status are significant risk factors for respiratory and RSV-related rehospitalisations.
Publisher: Wiley
Date: 16-04-2021
DOI: 10.1111/JPC.15507
Abstract: Almost exactly 10 years after the publication of ‘Call for a national plan for rare diseases’ in this journal, the Federal Government launched the National Strategic Action Plan for Rare Diseases (the Action Plan) on the 26th of February 2020, in the lead up to Rare Disease Day on the 29th of February – a rare day for rare diseases. The Action Plan is the culmination of effective advocacy by Rare Voices Australia (RVA) and other stakeholders in the rare disease (RD) sector. RVA is the peak body for Australians living with a RD. The organisation works collaboratively with RD organisations, researchers and clinicians. Since the initial call for a RD plan, a number of health‐care initiatives and policy changes have gathered apace including expanded antenatal and newborn screening, the increasing application of next generation sequencing and advances in gene and cell therapeutics. The development of new models of care, diagnostic and treatment pathways, and communities of practice have started to ease the considerable burden and inequitable access to care experienced by RD patients and their families. However, much work remains to be done. The Action Plan outlines the actions to bring about the best possible health and well‐being outcomes for Australians living with RD. It is centred around three pillars – awareness and education, care and support, research and data – and will be delivered against the principles of person centredness, equity, and sustainable systems and workforce.
Publisher: Wiley
Date: 2005
DOI: 10.1002/PPUL.20251
Abstract: The incidence of empyema complicating community-acquired pneumonia is increasing and causes significant childhood morbidity. Pneumococcal infection remains the most common isolated cause in developed countries, with Staphylococcus aureus the predominant pathogen in the developing world. Newer molecular techniques utilizing the polymerase chain reaction have led to an increase in identification of causative bacteria, previously not isolated by conventional culture techniques. This remains an important epidemiological tool, and may help in guiding correct antibiotic use in the future. There are many treatment options, however, and the care a child currently receives is dependent on local practice, which is largely determined by availability of medical personnel and their preferences. Although there are many reported case series comparing treatment options, only two randomized controlled studies exist to guide treatment in children. There is an urgent need for this to be addressed, particularly with the introduction of relatively new surgical techniques such as video-assisted thorascopic surgery.
Publisher: BMJ
Date: 07-2020
DOI: 10.1136/BMJRESP-2020-000593
Abstract: Detection of pneumonia-causing respiratory viruses in the nasopharynx of asymptomatic children has made their actual contribution to pneumonia unclear. We compared nasopharyngeal viral density between children with and without pneumonia to understand if viral density could be used to diagnose pneumonia. Nasopharyngeal swabs (NPS) were collected from hospitalised pneumonia cases at Princess Margaret Hospital (PMH) and contemporaneous age-matched controls at PMH outpatient clinics and a local immunisation clinic in Perth, Australia. The density (copies/mL) of respiratory syncytial virus (RSV), influenza A virus (InfA), human metapneumovirus (HMPV) and rhinovirus in NPS was determined using quantitative PCR. Linear regression analysis was done to assess the trend between viral density and age in months. The association between viral density and disease status was examined using logistic regression. Area under receiver operating characteristic (AUROC) curves were assessed to determine optimal discriminatory viral density cut-offs. Through May 2015 to October 2017, 230 pneumonia cases and 230 controls were enrolled. Median nasopharyngeal density for any respiratory virus was not substantially higher in cases than controls (p .05 for each). A decreasing density trend with increasing age was observed—the trend was statistically significant for RSV (regression coefficient −0.04, p=0.004) but not for other viruses. After adjusting for demographics and other viral densities, for every log 10 copies/mL density increase, the odds of being a case increased by six times for RSV, three times for HMPV and two times for InfA. The AUROC curves were .70 for each virus, suggesting poor case–control discrimination based on viral density. The nasopharyngeal density of respiratory viruses was not significantly higher in children with pneumonia than those without however, the odds of being a case increased with increased density for some viruses. The utility of viral density, alone, in defining pneumonia was limited.
Publisher: BMJ
Date: 23-07-2009
Publisher: European Respiratory Society (ERS)
Date: 26-04-2006
DOI: 10.1183/09031936.06.00063505
Abstract: The aim of this study was to develop a technique for the collection of exhaled breath condensate (EBC) from ventilated children and assess its safety and feasibility. Collection of EBC is used to investigate markers of oxidative stress in the lower airway. No studies have assessed its safety in ventilated children. An in vitro model was developed by connecting a ventilator to an artificial lung 14 clinical and ventilatory parameters were measured during EBC collection from ventilated children. Levels of 8-isoprostane were measured following collection with and without humidification of the inhaled gas. Amount of water vapour collected was linearly related to time and to minute ventilation in the in vitro model. EBC collections (n = 68) were made from ventilated children. In the nonhumidified group, the mean (range) positive end-expiratory pressure increased by 4.1% (2.8-5.5%) and the peak inspiratory flow decreased by 6.1% (11.0-1.3%) during collection. Detectable levels of 8-isoprostane were only found in 10 out of 18 nonhumidified EBC s les (median (range) 4.7 pg x mL(-1) (0-5.8)). Collection of exhaled breath condensate from ventilated infants and children is feasible and safe. Discontinuation of humidification is likely to be important in standardising the measurement of inflammatory parameters in exhaled breath condensate collected from ventilated children.
Publisher: BMJ
Date: 23-07-2012
Abstract: During air flight, cabin pressurisation produces an effective fraction of inspired oxygen (FiO(2)) of 0.15. This can cause hypoxia in predisposed in iduals, including infants with bronchopulmonary dysplasia (BPD), but the effect on ex-preterm babies without BPD was uncertain. The consequences of feeding a baby during the hypoxia challenge were also unknown. Ex-preterm (without BPD) and term infants had fitness to fly tests (including a period of feeding) at 3 or 6 months corrected gestational age (CGA) in a body plethysmograph with an FiO(2) of 0.15 for 20 min. A 'failed' test was defined as oxygen saturation (SpO(2)) <90% for at least 2 min. 41 term and 30 ex-preterm babies (mean gestational age 39.8 and 33.1 weeks, respectively) exhibited a significant median drop in SpO(2) (median -6%, p<0.0001) there was no difference between term versus ex-preterm babies, or 3 versus 6 months. Two term (5%) and two ex-preterm (7%) babies failed the challenge. The SpO(2) dropped further during feeding (median -4% in term and -2% in ex-preterm, p<0.0001), with transient desaturation (up to 30 s) <90% seen in 8/36 (22%) term and 9/28 (32%) ex-preterm infants the ex-preterm babies desaturated more quickly (median 1 vs 3 min, p=0.002). Ex-preterm babies without BPD and who are at least 3 months CGA do not appear to be a particularly at-risk group for air travel, and routine preflight testing is not indicated. Feeding babies in an FiO(2) of 0.15 leads to a further fall in SpO(2), which is significant but transient.
Publisher: MyJove Corporation
Date: 10-11-2021
DOI: 10.3791/63090-V
Publisher: American Academy of Pediatrics (AAP)
Date: 12-2021
Abstract: The validity of oropharyngeal swabs obtained by parents is described, and a case for parent-collection to be used as part of remote care is presented.
Publisher: BMJ
Date: 05-2023
Publisher: Elsevier BV
Date: 10-2019
Publisher: Frontiers Media SA
Date: 06-2023
DOI: 10.3389/FMOLB.2023.1148501
Abstract: Background: Cystic fibrosis (CF) is caused by a wide spectrum of mutations in the CF transmembrane conductance regulator ( CFTR ) gene, with some leading to non-classical clinical presentations. We present an integrated in vivo, in silico and in vitro investigation of an in idual with CF carrying the rare Q1291H -CFTR allele and the common F508del allele. At age 56 years, the participant had obstructive lung disease and bronchiectasis, qualifying for Elexacaftor/Tezacaftor/Ivacaftor (ETI) CFTR modulator treatment due to their F508del allele. Q1291H CFTR incurs a splicing defect, producing both a normally spliced but mutant mRNA isoform and a misspliced isoform with a premature termination codon, causing nonsense mediated decay. The effectiveness of ETI in restoring Q1291H-CFTR is largely unknown. Methods: We collected clinical endpoint measurements, including forced expiratory volume in 1 s percent predicted (FEV1pp) and body mass index (BMI), and examined medical history. In silico simulations of the Q1291H-CFTR were compared to Q1291R, G551D, and wild-type (WT)-CFTR. We quantified relative Q1291H CFTR mRNA isoform abundance in patient-derived nasal epithelial cells. Differentiated pseudostratified airway epithelial cell models at air liquid interface were created and ETI treatment impact on CFTR was assessed by electrophysiology assays and Western blot. Results: The participant ceased ETI treatment after 3 months due to adverse events and no improvement in FEV1pp or BMI. In silico simulations of Q1291H-CFTR identified impairment of ATP binding similar to known gating mutants Q1291R and G551D-CFTR. Q1291H and F508del mRNA transcripts composed 32.91% and 67.09% of total mRNA respectively, indicating 50.94% of Q1291H mRNA was misspliced and degraded. Mature Q1291H-CFTR protein expression was reduced (3.18% ± 0.60% of WT/WT) and remained unchanged with ETI. Baseline CFTR activity was minimal (3.45 ± 0.25 μA/cm 2 ) and not enhanced with ETI (5.73 ± 0.48 μA/cm 2 ), aligning with the in idual’s clinical evaluation as a non-responder to ETI. Conclusion: The combination of in silico simulations and in vitro theratyping in patient-derived cell models can effectively assess CFTR modulator efficacy for in iduals with non-classical CF manifestations or rare CFTR mutations, guiding personalized treatment strategies and optimizing clinical outcomes.
Publisher: MDPI AG
Date: 21-05-2023
DOI: 10.3390/JPM13050864
Abstract: Primary nasal epithelial cells and culture models are used as important diagnostic, research and drug development tools for several airway diseases. Various instruments have been used for the collection of human nasal epithelial (HNE) cells but no global consensus yet exists regarding the optimal tool. This study compares the efficiency of two cytology brushes (Olympus (2 mm diameter) and Endoscan (8 mm diameter)) in collecting HNE cells. The study involved two phases, with phase one comparing the yield, morphology and cilia beat frequency (CBF) of cells collected from paediatric participants using each of the two brushes. Phase two compared nasal brushing under general anaesthetic and in the awake state, across a wide age range, via the retrospective audit of the use of the Endoscan brush in 145 participants. Results indicated no significant difference in CBF measurements between the two brushes, suggesting that the choice of brush does not compromise diagnostic accuracy. However, the Endoscan brush collected significantly more total and live cells than the Olympus brush, making it a more efficient option. Importantly, the Endoscan brush is more cost-effective, with a notable price difference between the two brushes.
Publisher: Springer Science and Business Media LLC
Date: 09-09-2021
DOI: 10.1038/S41533-021-00253-9
Abstract: Asthma is the most common chronic condition of childhood. Self-management is integral to good asthma control. This qualitative paper explores how children with asthma and their parents perceive asthma, their experience with asthma, and how they manage symptoms, preventions and medications within and outside the home. We undertook 15 focus groups with 41 school-aged (6–11 years) children with asthma and 38 parents. Parents and their children attended the same focus groups. We used thematic analysis to analyse the transcripts. Our findings show the impact asthma can have on children’s social and emotional wellbeing and highlight how reliant school-aged children are on their parents to effectively manage their asthma. Parents reported being unsure when their child’s symptoms warranted visiting their doctor or hospital. Schools were identified as a source of difficulty regarding asthma management families reported that children may be self-conscious about their asthma and using their inhaler at school. School policies and teachers’ lack of asthma knowledge were reported to exacerbate children’s reluctance to use their inhaler at school. Our results have implications for the design and implementation of children’s self-management interventions for their asthma, particularly when they are at school and away from their parents.
Publisher: IOP Publishing
Date: 24-11-2014
DOI: 10.1088/1752-7155/8/4/046009
Abstract: Exhaled breath analysis is able to identify biomarkers of respiratory and systemic diseases. It was hypothesized that markers of pancreatic function would be identified in the breath of those with diabetes mellitus and cystic fibrosis. Children aged 6-18 years old with diabetes mellitus (DM), cystic fibrosis (CF), cystic fibrosis related diabetes (CFRD) and healthy controls (C) contributed exhaled breath condensate (EBC), with concurrent blood glucose measurements taken from a subset. EBC C-peptide, glucose, sodium concentrations and conductivity were subsequently measured.A total of 104 children were recruited (DM = 56, CF = 26, CFRD = 5, C = 17). C-peptide was detected in EBC: CF 19.6 ± 11.7 pmol L(-1) DM: 9.66 ± 8.27 pmol L(-1) CFRD: 11.9 ± 9.23 pmol L(-1) which was significantly higher than in the control group (0.987 ± 2.26 pmol L(-1)) (p < 0.0001). No statistically significant difference was seen between the three groups for glucose, conductivity or sodium concentration.Glucose was not reliably found in EBC, but C-peptide was found to be higher in CF EBC. This may represent inflammation and a change in airway integrity, rather than increased secretion of this peptide.
Publisher: Springer Basel
Date: 2016
Publisher: Wiley
Date: 2019
DOI: 10.1111/JPC.14300
Publisher: Public Library of Science (PLoS)
Date: 31-07-2012
Publisher: Wiley
Date: 10-02-2021
DOI: 10.1002/HSR2.241
Publisher: BMJ
Date: 08-04-2015
Publisher: BMJ
Date: 08-04-2015
Publisher: Informa UK Limited
Date: 07-2021
DOI: 10.2147/JAA.S311721
Publisher: American Thoracic Society
Date: 02-2016
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.BRAT.2016.11.004
Abstract: Anxiety disorders are highly prevalent in children with asthma yet very little is known about the cognitive and parent factors that may underpin this relationship. The present study investigated interpretation biases in children with asthma and anxiety and their parents, and whether parent-child discussions influenced children's interpretations. Eighty-nine parent-child dyads were included across four groups: children with asthma and anxiety, children with anxiety only, children with asthma only and healthy children (aged between 8 and 13 years old). Interpretation bias was assessed using ambiguous scenarios. Children with anxiety showed an interpretation bias in the general threat scenarios, whereas children with asthma showed an interpretation bias in the asthma threat scenarios. Parental predictions of their child's responses showed similar results. Parent-child discussions increased avoidance for children with anxiety and no asthma across all scenarios, but only for children with asthma and anxiety in the asthma threat scenarios. The results provide partial support for a cognitive theory of asthma and anxiety in children and suggest that parents play a role in influencing children's thinking styles. Treatment programs could thus aim to target and modify interpretation biases in children with anxiety, and include parents as part of treatment.
Publisher: BMJ
Date: 03-2009
Abstract: Non-cystic fibrosis (non-CF) bronchiectasis often starts in childhood with a significant impact on adult morbidity. Little is known about disease progression through childhood and the effect on growth and spirometry. This study reviews longitudinal lung function and growth in children with non-CF bronchiectasis. The case notes of patients with non-CF bronchiectasis were reviewed retrospectively. Patients were included if at least three calendar years of lung function data were available. Anthropometric measurements and annual spirometry were analysed over both two and four consecutive years. Changes over time were assessed using Generalised Estimating Equations. Fifty-nine patients (31 boys) were identified. At baseline the median age was 8.2 years (range 4.8-15.8), the mean (SD) for height, weight and body mass index (BMI) for age z-scores were -0.68 (1.31), -0.19 (1.34) and 0.19 (1.38), respectively. At baseline, the mean (SD) z-score for forced expiratory volume in 1 s (FEV(1)) was -2.61 (1.82). Over 2 years (n = 59), mean FEV(1) and forced vital capacity (FVC) improved by 0.17 (95% CI 0.01 to 0.34, p = 0.039) and 0.21 (95% CI 0.04 to 0.39, p = 0.016) z-scores per annum, respectively. Over 4 years there was improvement in height-for-age z-scores (slope 0.05, 95% CI 0.01 to 0.095, p = 0.01) but no improvement in other anthropometric variables. There was no change in spirometry (FEV(1) slope 0.00, 95% CI -0.09 to 0.09, p = 0.999 and FVC slope 0.09, 95% CI -0.09 to 0.1, p = 0.859). Children with non-CF bronchiectasis show adequate growth over time. Lung function stabilises but does not normalise with treatment, underscoring the need for early detection and institution of appropriate therapy.
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: Frontiers Media SA
Date: 23-09-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2015
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.JCF.2017.07.011
Abstract: The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract. M2-PK was measured in stools collected from patients with CF and HC (0-10years). Linear mixed model analysis was used. M2-PK levels did not significantly change in children with CF (36 patients, 77 s les) (P=0.998) or HC (45 patients, 45 s les) (P=0.21), over the age range 0-10years. Patients with CF had elevated M2-PK compared to HC (median [IQR range]: 10.7 [5.7-28.6 1.0-239.1] (n=77) vs. 1.0 [1.0-1.0 1.0-50.0] (n=45) U/mL, respectively P=0.001). Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.PRRV.2009.12.003
Abstract: Interest in azithromycin in the management of patients with cystic fibrosis has grown over the last decade. Uniquely this drug has both antibacterial and immune modulating effects which appear to be the reason for its clinical benefit as proven in several well designed clinical studies. In this review we discuss the proposed mechanisms of action of azithromycin and review the evidence for its clinical effectiveness and safety in cystic fibrosis.
Publisher: MDPI AG
Date: 30-11-2020
Abstract: Systemic glutathione deficiency, inflammation, and oxidative stress are hallmarks of cystic fibrosis (CF), an inherited disease that causes persistent lung infections and severe damage to the respiratory system and many of the body organs. Improvements to current antioxidant therapeutic strategies are needed. The dietary supplement, γ-glutamylcysteine (GGC), which is the immediate precursor to glutathione, rapidly boosts cellular glutathione levels following a single dose in healthy in iduals. Efficacy of GGC against oxidative stress induced by Pseudomonas aeruginosa, which is a common and chronic pathogen infecting lungs of CF patients, remains unassessed. Primary mucocilliary differentiated airway (bronchial and/or nasal) epithelial cells were created from four in iduals with CF. Airway oxidative stress and inflammation was induced by P. aeruginosa lipopolysaccharide (LPS). Parameters including global proteomics alterations, cell redox state (glutathione, oxidative stress), pro-inflammatory mediators (IL-8, IDO-1), and cellular health (membrane integrity, stress granule formation, cell metabolic viability) were assayed under six experimental conditions: (1) Mock, (2) LPS-challenged (3) therapeutic, (4) prophylactic (5) therapeutic and prophylactic and (6) GGC alone. Proteomic analysis identified perturbation of several pathways related to cellular respiration and stress responses upon LPS challenge. Most of these were resolved when cells were treated with GGC. While GGC did not resolve LPS-induced IL-8 and IDO-1 activity, it effectively attenuated LPS-induced oxidative stress and stress granule formation, while significantly increasing total intracellular glutathione levels, metabolic viability and improving epithelial cell barrier integrity. Both therapeutic and prophylactic treatments were successful. Together, these findings indicate that GGC has therapeutic potential for treatment and prevention of oxidative stress-related damage to airways in cystic fibrosis.
Publisher: Wiley
Date: 20-10-2010
DOI: 10.1002/PPUL.21349
Abstract: Empyema is a complication of pneumonia, commonly caused by Streptococcus pneumoniae. To validate the utility of an immunochromatographic test for the detection of S. pneumoniae antigen in the pleural fluid of children with empyema. Empyema patients had blood and pleural fluid cultured, and polymerase chain reaction (PCR) to detect the S. pneumoniae autolysin gene, lytA, in pleural fluid. Pleural fluid was tested using the Binax NOW S. pneumoniae antigen detection assay and compared with lytA PCR results and/or culture in blood or pleural fluid. S. pneumoniae was detected by PCR in pleural fluid of 68 of 137 (49.6%) patients, by culture in 11 of 135 (8.1%) pleural specimens and 16 of 120 (13.3%) blood specimens. Pleural fluid Binax NOW testing from 130 patients demonstrated a sensitivity of 83.8% and specificity of 93.5% (positive predictive value of 93.4% and negative predictive value of 84.1%). In pediatric empyema, high predictive values of pleural fluid Binax NOW S. pneumoniae antigen test suggest that this test may help rationalize antibiotic choice in these patients.
Publisher: Springer Science and Business Media LLC
Date: 12-07-2001
Abstract: Krypton ventilation scans (VS) provide an index of peripheral lung function, and may be particularly useful in children unable to perform pulmonary function testing. This communication reports on three linked studies which investigated whether a routine VS in young children with cystic fibrosis (CF) is diagnostically or prognostically useful. Study 1: In a preliminary study in 1991, VS were compared with clinical examination and chest radiography (CXR) in 50 CF children (29 females, 21 males) aged 0.4-5.2 years (median 2.2 years). The chest was ided into six zones, and abnormalities scored from 0 (normal) to 2 (very abnormal). Clinical examination was unhelpful in predicting abnormalities on imaging. In five children (10%) with a normal CXR, VS was abnormal, and in a further eight children (16%), CXR markedly underestimated VS changes. Study 2: In order to determine the long-term prognostic significance of VS abnormalities, we followed up 27 (19 females, 8 males) of the children from study 1, who had had their first VS at presentation at median age 1.6 years (range 0.4-5.2), scoring the same six zones from 0 to 2. Follow-up was for a mean of 11.6 years (range 7.8-14.8). Spirometry at age 7 years showed a mean forced expiratory volume in 1 s (FEV1) of 96% (range 46%-145%) and a mean forced vital capacity (FVC) of 96% (range 46%-145%). A poor VS score at presentation was correlated with percent predicted FEV1 at age 7 (r=0.4, P=0.042, 16% of variance explained). Those with a normal VS at presentation had a mean FEV1 at presentation of 99% (range 80%-129%). Whereas four patients had an abnormal VS, a normal CXR and a low FEV1 at age 7 years, no patient had a normal VS, an abnormal CXR and a low FEV1 at age 7 years. Study 3: Fifty children (29 females, 21 males) aged 0.5-6.0 years (median 3.8) were prospectively studied in 1998, to determine whether the findings in study 1 were stable over time, and to assess whether VS altered clinical management. Symptoms and clinical examination did not predict abnormalities on imaging. Thirty (60%) children had a normal VS while only five (10%) had a normal CXR. There was a significant correlation between the total scores of CXR and VS (P=0.007, 14% of variance explained). Further, VS detected additional abnormalities in seven patients (14%). Sixty-five percent of patients with an abnormal VS had modifications of treatment, including bronchoscopy, compared with 23% of those with a normal VS. We conclude that VS is a simple, safe and non-invasive technique giving additional information to that provided by clinical examination and chest radiography in a number of children with CF and can be used to modify clinical management. VS at presentation gives prognostic information, which may be of use in early intervention studies. Whether using VS to guide treatment improves long-term prognosis requires a larger prospective trial.
Publisher: BMJ
Date: 02-10-2018
DOI: 10.1136/ARCHDISCHILD-2018-315628
Abstract: Chronic conditions are the leading cause of mortality, morbidity and disability in children. However, children and caregivers are rarely involved in identifying research priorities, which may limit the value of research in supporting patient-centred practice and policy. To identify priorities of patients, caregivers and health professionals for research in childhood chronic conditions and describe the reason for their choices. An Australian paediatric hospital and health consumer organisations. Recruited participants (n=73) included patients aged 8 to 14 years with a chronic condition (n=3), parents/caregivers of children aged 0 to 18 years with a chronic condition (n=19), representatives from consumer organisations (n=13) and health professionals including clinicians, researches (n=38) identified and discussed research priorities. Transcripts were thematically analysed. Seventy-eight research questions were identified. Five themes underpinned participants’ priorities: maintaining a sense of normality (enabling participation in school, supporting social functioning, promoting understanding and acceptance), empowering self-management and partnership in care (overcoming communication barriers, gaining knowledge and skills, motivation for treatment adherence, making informed decisions, access and understanding of complementary and alternative therapies),strengthening ability to cope (learning to have a positive outlook, preparing for home care management, transitioning to adult services), broadening focus to family (supporting sibling well-being, parental resilience and financial loss, alleviating caregiver burden), and improving quality and scope of health and social care (readdressing variability and inequities, preventing disease complications and treatment side effects, identifying risk factors, improving long-term outcomes, harnessing technology, integrating multidisciplinary services). Research priorities identified by children, caregivers and health professionals emphasise a focus on life participation, psychosocial well-being, impact on family and quality of care. These priorities may be used by funding and policy organisations in establishing a paediatric research agenda.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2004
Publisher: Springer Science and Business Media LLC
Date: 04-05-2016
DOI: 10.1038/SREP24857
Abstract: Cystic fibrosis (CF) is a genetic disorder that leads to formation of thick epithelial secretions in affected organs. Chronic microbial infections associated with thick mucus secretions are the hallmarks of lung disease in CF. Despite similar conditions existing in the gastrointestinal tract, it is much less studied. We therefore examined the microbial communities within the gastrointestinal tract of children with and without CF (either pancreatic sufficient or insufficient) across a range of childhood ages (0.87–17 years). We observed a substantial reduction in the richness and ersity of gut bacteria associated with CF from early childhood (2 years) until late adolescence (17 years). A number of bacteria that establish themselves in the gut of healthy children were unable to do so in children with CF. In contrast, a few bacteria dominated the gut microbiota in children with CF and are unlikely to be beneficial for the metabolic function of the gut. A functioning pancreas (pancreatic sufficient) under a CF lifestyle showed little effect on microbial communities. Our results argue that any attempts to rectify the loss of bacterial ersity and provide normal bacterial function in the gut of CF patients should be conducted no later than early childhood.
Publisher: Elsevier BV
Date: 05-2014
Publisher: Springer Science and Business Media LLC
Date: 2002
DOI: 10.2165/00128072-200204060-00005
Abstract: A group of patients with cystic fibrosis (CF) have severe small airways disease characterized by wheeze, chest tightness and limited sputum production, often with deteriorating lung function. Suggested mechanisms include mucosal edema secondary to infection and inflammation, smooth muscle contraction caused by inflammatory mediators, and collapse of bronchiectatic airways. While treatment with long-term oral corticosteroids may result in symptomatic improvement, adverse effects often make them intolerable. Inhaled corticosteroids are used in many centers despite the lack of conclusive evidence of their efficacy. Therapeutic alternatives to corticosteroids are aimed at reversing bronchoconstriction and reducing inflammation. Many patients with CF are treated with short- and long-term inhaled bronchodilators, but data to support their use are inconclusive. Other attempted routes of administration for short-acting bronchodilators include the subcutaneous and intravenous routes, but clinical data are again lacking. Sodium cromoglycate (cromolyn sodium) has been studied, with little evidence of benefit. Theophyllines have also been studied, both intravenously and orally, with some effect, but are not often used in clinical practice. Nonsteroidal anti-inflammatory therapies include ibuprofen, macrolide antibiotics, intravenous immunoglobulin, cyclosporine, and leukotriene antagonists. Ibuprofen has been shown to be useful in patients with mild CF disease, but concerns about potential adverse effects have limited its use. The results of various macrolide studies are awaited, but to date there are no long-term studies published. While there is great interest in the potential of intravenous immunoglobulin, cyclosporine and leukotriene antagonists, the evidence for their effectiveness comes from anecdotal reports, thus there is currently insufficient data to support their use. Since this is a small group of patients, it is unlikely that sufficient numbers will ever be recruited for these studies thus it is probable that drugs will be tried on an in idual patient basis. The order in which they are attempted is unclear, but it would be sensible to try the least invasive medication with the least adverse effects first, moving on to more potent, but more toxic drugs if that treatment fails.
Publisher: American Thoracic Society
Date: 08-2013
Publisher: Elsevier BV
Date: 07-2009
Publisher: BMJ
Date: 08-04-2015
Publisher: Springer Basel
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 06-2006
DOI: 10.1203/01.PDR.0000219395.83159.91
Abstract: Arm anthropometry is used as a proxy of body composition in clinical and field research but its validity has not been established in children. To address this issue, mid-upper arm circumference (MUAC) and triceps skinfold thickness (TS) were measured in 110 healthy children aged 4.4-13.9 y (55 boys) and 49 cystic fibrosis (CF) patients aged 8.1-13.4 y (22 boys). Reference values were arm and whole-body fat mass (FM) and fat-free mass (FFM) measured by dual x-ray absorptiometry and four-component model, respectively. Arm fat area (AFA), MUAC, and TS correlated well with arm FM (r = 0.84-0.92) and total FM (r = 0.78-0.92). Arm muscle area (AMA) and MUAC correlated well with arm FFM (r = 0.68-0.82) and total FFM (r = 0.60-0.86). After adjusting for age, sex, and height, arm anthropometry correlated strongly with FM but weakly with FFM. AFA, MUAC, and TS explained 67, 63, and 61% of variability in total FM in healthy children and 70, 72, and 63% in CF. AMA and MUAC explained only 24 and 16% of variability in total FFM in healthy children and 33 and 28% in CF. Arm anthropometry is useful for predicting FM and ranking healthy children and patients for fatness. It has poorer success in predicting regional or total FFM.
Publisher: Wiley
Date: 30-07-2016
DOI: 10.1002/JMV.24325
Abstract: Nosocomial transmission of respiratory syncytial virus (RSV) occurs in children within the neonatal intensive care unit (NICU). During peak community RSV transmission, three swabs were collected from the nose, hand and personal clothing of visitors and health care workers (HCW) in NICU once every week for eight weeks. Nasal swabs were collected from every third neonate and from any neonate clinically suspected of having a respiratory infection. Environmental s ling of high touch areas was done once during the study period. All swabs were tested for RSV using real time RT-PCR. There were 173 (519 total) and 109 (327 total) swabs, each of nose, hand and dress from 84 HCWs and 80 visitors respectively and 81 nasal swabs from 55 neonates collected. Thirty five environmental swabs from surfaces of the beds, side tables, counter tops, chairs, tables and computers were collected. Overall 1% of nasal swabs from each of HCWs, visitors and neonates, 4% of dress specimens from visitors and 9% of environmental swabs were positive for RSV-RNA. The results suggest that though the risk for RSV in the NICU remains low, personnel clothing are contaminated with RSV-RNA and may have a role in transmission.
Publisher: Elsevier BV
Date: 2015
Publisher: SAGE Publications
Date: 16-07-2022
DOI: 10.1177/13674935211033466
Abstract: Siblings of young people with chronic illness commonly undertake caring responsibilities for their affected brother/sister, which may encourage maturation, yet may also be perceived as a burden. Our study determined (1) siblings’ caring responsibilities, (2) siblings’ current emotional distress and psychosocial functioning, and (3) how siblings’ caring responsibilities and psychosocial functioning related to familial relationships and coping strategies. Siblings completed questionnaires which contained Sibling Inventory of Behavior, Sibling Inventory of Differential Experiences, PedsQL, emotion thermometers, Brief COPE, and a checklist of caregiving responsibilities. We analyzed the data with t-tests and multi-level models. Forty-five siblings (mean age = 15.40 years, SD = 3.31 years 60.0% female) participated. Siblings who had caring responsibilities ( n = 26, 57.8%) reported lower anxiety symptoms, lower need for help, greater use of problem-focused coping, and more companionship and teaching/directiveness with their affected brother/sister than siblings without caring responsibilities. Siblings reported lower psychosocial and physical functioning when they perceived their parents provided them with less affection than their affected brother/sister. Family-based psychosocial interventions may aim to improve the sibling–parent relationship (including expressing affection) and the sibling–sibling relationship. Future interventions may also focus on increasing siblings’ use of problem-focused coping strategies.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2021
DOI: 10.1186/S13223-021-00522-9
Abstract: We conducted a systematic review and meta-analysis to determine the effectiveness of comprehensive community-based interventions with ≥ 2 components in improving asthma outcomes in children. A systematic search of Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE), Cochrane Library and hand search of reference collections were conducted to identify any research articles published in English between 2000 and 2019. All studies reporting community-based asthma interventions with ≥ 2 components (e.g., asthma self-management education, home environmental assessment or care coordination etc.) for children aged ≤ 18 years were included. Meta-analyses were performed using random-effects model to estimate pooled odds ratio (OR) with 95% confidence intervals (CIs). Of the 2352 studies identified, 21 studies were included in the final analysis: 19 pre-post interventions, one randomised controlled trial (RCT) and one retrospective study. Comprehensive asthma programs with multicomponent interventions were associated with significant reduction in asthma-related Emergency Department (ED) visits (OR = 0.26 95% CI 0.20–0.35), hospitalizations (OR = 0.24 95% CI 0.15–0.38), number of days (mean difference = − 2.58 95% CI − 3.00 to − 2.17) and nights with asthma symptoms (mean difference = − 2.14 95% CI − 2.94 to − 1.34), use of short-acting asthma medications/bronchodilators (BD) (OR = 0.28 95% CI 0.16–0.51), and increase use of asthma action plan (AAP) (OR = 8.87 95% CI 3.85–20.45). Community-based asthma care using more comprehensive approaches may improve childhood asthma management and reduce asthma related health care utilization.
Publisher: Elsevier BV
Date: 12-2010
Abstract: Malnutrition is an indicator of a poor prognosis in patients with cystic fibrosis (CF). Previous body-composition (BC) studies in children with CF used 2-component models (2CMs) to assess fat mass (FM) and fat-free mass (FFM), but to our knowledge no study has used the gold-standard 4-component model (4CM), which allows for a more accurate evaluation of the nature of both elements. We measured BC by using the 4CM in 6-12-y-old children with CF to 1) compare findings with those of healthy, matched control children and reference data 2) relate BC to lung spirometry [forced expired volume in 1 s (FEV₁)] and 3) compare findings with those from more commonly used 2CM techniques. One hundred clinically stable children with CF (57% girls) aged 6-12 y were measured by using the 4CM. Children with CF underwent spirometry (FEV₁). Girls with CF had significantly less FM than did healthy girls, even after adjustment for height and pubertal status boys with CF had higher body mass index SD scores than did healthy boys. FM in girls was positively associated with the FEV₁ percentage predicted. The 2CM FM was significantly different from the 4CM FM, with differences dependent on sex and condition, although most techniques identified a relation between FM and FEV₁ in girls. Although shorter than healthy children, boys with CF were heavier and had a BC within the normal range however, girls with CF had lower FM than did healthy girls, and this was associated with poorer lung function. Given the worse prognosis in girls, this finding merits more attention. The reliability of 2CM techniques varied with sex and health status.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Springer Science and Business Media LLC
Date: 2007
DOI: 10.2165/00148581-200709020-00004
Abstract: The macrolide antibiotics are a family of related 14- or 15-membered lactone ring antibiotics. There has been recent interest in the beneficial effects of these drugs as immune modulators in respiratory conditions in children. Cystic fibrosis (CF) and asthma, both of which occur in childhood, have an underlying inflammatory component and are associated with significant morbidity. The pathogenesis of both conditions is poorly understood but several molecular mechanisms have been suggested. In CF, these mechanisms broadly involve altered chloride transport and alteration of the airway surface liquid with disordered neutrophilic inflammation. There is much evidence for a proinflammatory propensity in CF immune effector and epithelial cells and many studies indicate that macrolides modulate these inflammatory processes. Recent studies have confirmed a clinical improvement in CF following treatment with macrolides, but the exact mechanisms by which they work are unknown. Asthma is likely to represent several different phenotypes but in all of these, airway obstruction, bronchial hyperresponsiveness, and inflammation are central processes. Results from trials using macrolides have suggested an improvement in clinical outcome. The putative mechanisms of macrolide immunomodulatory action include improvement of the primary defense mechanisms, inhibition of the bacteria-epithelial cell interaction, modulation of the signaling pathway and chemokine release, and direct neutrophil effects. Putative mechanisms of phenotypic modulation have also been proposed involving interactions with nitric oxide, endothelin-1, and bronchoconstriction, endothelial growth factors and airway remodeling, and bioactive phospholipids in both CF and asthma. Further characterization of these effects and development of targeted designer drugs will further expand our therapeutic repertoire and lead to improved quality and quantity of life for patients with CF and asthma.
Publisher: Springer Basel
Date: 2016
Publisher: Wiley
Date: 12-1999
DOI: 10.1002/(SICI)1099-0496(199912)28:6<449::AID-PPUL11>3.0.CO;2-H
Abstract: Ciprofloxacin, a quinolone antibiotic, is used to treat a wide variety of infections including Pseudomonas aeruginosa in patients with cystic fibrosis (CF). Photosensitivity is a well-known complication of treatment with this group of antibiotics, and it is more common in patients with CF. We report on a case of photosensitivity induced by indoor fluorescent strip-lighting (spectral range, 295-760 nm) in a 12-year-old girl with CF treated with ciprofloxacin. This type of lighting emits UVA rays (320-400 nm) which cause skin damage in the presence of sensitizing agents. Patients taking ciprofloxacin are usually advised to protect their skin from direct sunlight. We suggest that more attention should be paid to indoor sources of UV light.
Publisher: BMJ
Date: 04-07-2006
Publisher: Elsevier BV
Date: 12-2020
Publisher: BMJ
Date: 04-2010
Publisher: Wiley
Date: 14-03-2017
DOI: 10.1002/JMV.24794
Abstract: Rhinovirus (RV) is a common respiratory viral infection linked to worsening of chronic respiratory diseases including cystic fibrosis (CF) and asthma. RV was tested by RT-PCR in s les (n = 465) collected from the upper (nasal swab, oropharyngeal suction, and sputum) and lower (bronchoalveolar washings) respiratory tract of 110 children with CF. Air s les (n = 52) collected from the operating theatres and outpatient clinics were tested for RV. RV was found in 43% of children <5 years suffering an exacerbation, and 12% of older children (5-17 years). RV particles were detected in the air of clinic rooms. Detection of RV is important in better understanding viral infections in patients with CF.
Publisher: BMJ
Date: 12-03-2009
Abstract: Problems with sleep, eating and adherence to therapy may adversely affect health outcomes in children with cystic fibrosis (CF). Data on the prevalence of such problems, associated parenting styles and caregiver mental health are limited. To determine: (a) the prevalence of sleep, mealtime, therapy adherence and externalising and internalising behavioural problems in preschool children with CF (b) the prevalence of caregiver mental health problems and poor sleep quality and (c) associations between child behavioural problems and parenting styles. This was a cross sectional survey of caregivers of children aged 6 months to 5 years attending CF outpatient clinics at Royal Children's Hospital (Melbourne), Monash Medical Centre (Melbourne) and Sydney Children's Hospital. Main outcome measures were child externalising and internalising behaviours, sleep, eating and adherence with therapy the predictor was parenting styles (harsh, inconsistent, overprotective). 117 of 139 families participated. Problems were common with child sleep (small 31.6% moderate/large problem: 21.9%), eating (32.4%) and adherence with physiotherapy (50.4%). Compared to normative data, sleep and mealtime problems were more prevalent. Caregivers reported high rates of symptoms indicating depression (33.3%), anxiety (16.4%) and stress (34.2%). Harsh parenting was associated with internalising behaviours (adjusted OR 3.9, 95% CI 1.16 to 13.17, p = 0.03). Problems with sleeping, eating and physiotherapy adherence were common in preschool children with CF. Caregivers reported high rates of symptoms indicative of mental health problems. Harsh parenting was associated with internalising problems. An intervention targeting child problem behaviours and parental mental health would be appropriate for CF families.
Publisher: BMJ
Date: 12-2002
DOI: 10.1136/ADC.87.6.518
Abstract: To investigate whether routine annual assessment blood tests in cystic fibrosis (CF) patients under 5 years influence management. Retrospective review of the results of the first annual assessment blood tests of patients with CF less than 5 years of age during a four year period (1995-99). Management changes were identified from a follow up letter to the general practitioner or local paediatrician. A total of 169 patients (100 female), median age 2.2 years (range 0.3-4.9) were identified. Venepuncture was successful in 93% of patients. Of the 32 in idual blood parameters measured, the overall success rate in obtaining a result was 81%. Eleven per cent of patients underwent subsequent management changes, including liver ultrasound, fasting glucose, and a short course of iron. Of particular importance, vitamin A and E concentrations were low in 9% of patients, which prompted an increase in prescribed dose. These results support the recommendations for routine blood tests at annual review in preschool CF children. The results may help to rationalise which tests are performed and thus reduce laboratory costs.
Publisher: BMJ
Date: 27-01-2021
DOI: 10.1136/THORAXJNL-2020-216032
Abstract: Empyema is a serious complication of pneumonia frequently caused by Streptococcus pneumoniae (SP). We assessed the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema after inclusion in the Australian National Immunisation Program. For bacterial pneumonia and empyema hospitalisations, we ascertained incidence rates (IRs) using the National Hospital Morbidity Database International Statistical Classification of Disease discharge codes and relevant population denominators, and calculated incidence rate ratios (IRR) comparing the 13vPCV period (June 2012–May 2017) with the 7vPCV period (June 2007–May 2011). Blood and pleural fluid (PF) cultures and PF PCR of 401 children with empyema from 11 Australian hospitals during the 13vPCV period were compared with our previous study in the 7vPCV period. Across 7vPCV and 13vPCV periods, IRs per million children (95% CIs) were 1605 (1588 to 1621) and 1272 (1259 to 1285) for bacterial pneumonia, and 14.23 (12.67 to 15.79) and 17.89 (16.37 to 19.42) for empyema hospitalisations. IRRs were 0.79 (0.78 to 0.80) for bacterial pneumonia and 1.25 (1.09 to 1.44) for empyema. Of 161 empyema cases with SP serotypes, 147 (91.3%) were vaccine types. ST3 accounted for 76.4% of identified serotypes in the 13vPCV period, more than double than the 7vPCV period (p .001) ST19A decreased from 36.4% to 12.4%. No cases of ST1 empyema were identified in the 13vPCV period versus 14.5% in the 7vPCV period. 13vPCV resulted in a significant reduction in all-cause hospitalisations for bacterial pneumonia but empyema hospitalisations significantly increased, with emergence of pneumococcal ST3 as the dominant serotype in empyema. Australian and New Zealand Clinical Trial Registry ACTRN 12614000354684.
Publisher: Wiley
Date: 26-11-2007
DOI: 10.1002/PPUL.20684
Abstract: We report a case of pneumothorax as a result of positive pressure ventilation in a child previously treated for empyema. Three months following discharge for successful treatment of empyema our patient received a general anesthetic for an elective MRI of the brain for investigation of nystagmus. During recovery from the anesthetic he developed respiratory distress and was found to have a loculated pneumothorax. We propose that pleural fragility in childhood empyema possibly persists even after clinical resolution and in this case for up to 3 months. The complication of pneumothorax should be considered in all patients receiving positive pressure ventilation following resolved empyema.
Publisher: European Respiratory Society (ERS)
Date: 30-10-2014
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 08-2019
Publisher: American Thoracic Society
Date: 15-04-2012
Publisher: Elsevier BV
Date: 2003
DOI: 10.1067/MTC.2003.88
Publisher: Elsevier BV
Date: 06-2013
Publisher: Springer Science and Business Media LLC
Date: 16-06-2022
Publisher: BMJ
Date: 02-04-2019
DOI: 10.1136/BMJQS-2018-009028
Abstract: Bronchiolitis is the most common cause of respiratory hospitalisation in children aged years. Clinical practice guidelines (CPGs) suggest only supportive management of bronchiolitis. However, the availability of CPGs do not guarantee that they are used appropriately and marked variation in the clinical management exists. We conducted an assessment of guideline adherence in the management of bronchiolitis in children at a subnationally representative level including inpatient and ambulatory services in Australia. We searched for national and international CPGs relating to management of bronchiolitis in children and identified 16 recommendations which were formatted into 40 medical record audit indicator questions. A retrospective medical record review assessing compliance with the CPGs was conducted across three types of healthcare setting: hospital inpatient admissions, emergency department (ED) presentations and general practice (GP) consultations in three Australian states for children aged years receiving care in 2012 and 2013. Purpose-trained surveyors conducted 13 979 eligible indicator assessments across 796 visits for bronchiolitis at 119 sites. Guideline adherence for management of bronchiolitis was 77.3% (95% CI 72.6 to 81.5) for children attending EDs, 81.6% (95% CI 78.0 to 84.9) for inpatients and 52.3% (95% CI 44.8 to 59.7) for children attending GP consultations. While adherence to some in idual indicators was high, overall adherence to documentation of 10 indicators relating to history taking and examination was poorest and estimated at 2.7% (95% CI 1.5 to 4.4). The study is the first to assess guideline-adherence in both hospital (ED and inpatient) and GP settings. Our study demonstrated that while the quality of care for bronchiolitis was generally adherent to CPG indicators, specific aspects of management were deficient, especially documentation of history taking.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/571609
Abstract: Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Elsevier BV
Date: 03-2016
Publisher: Wiley
Date: 16-10-2022
DOI: 10.1002/JMV.27383
Abstract: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection hospitalisations in Aboriginal infants specifically those aged months. Maternally derived RSV antibody (Ab) can protect against severe RSV disease in infancy. However, the efficiency of transplacental transfer of maternal anti‐RSV Ab remains unknown in Aboriginal infants. We characterised RSV Ab in Australian First Nations mother‐infant pairs ( n = 78). We investigated impact of covariates including low birthweight, gestational age (GA), sex of the baby, maternal age and multiparity of the mother on cord to maternal anti‐RSV Ab titre ratio (CMTR) using multivariable logistic regression model. All ( n = 78) but one infant was born full term (median GA: 39 weeks, interquartile range: 38–40 weeks) and 56% were males. The mean log 2 RSV Ab titre was 10.7 ( SD ± 1.3) in maternal serum and 11.0 ( SD ± 1.3) in cord serum at birth a ratio of 1.02 ( SD ± 0.06). One‐third of the pairs had a CMTR of indicating impaired transfer. Almost 9% (7/78) of the term infants had cord RSV Ab levels below log 2 9. Covariates showed no effect on CMTR. Further mechanistic research is needed to determine the significance of these findings on RSV disease in First Nations children.
Publisher: Elsevier BV
Date: 2021
Publisher: Cold Spring Harbor Laboratory
Date: 31-05-2020
DOI: 10.1101/2020.05.29.120006
Abstract: Patient-derived airway cells differentiated at Air Liquid Interface (ALI) are valuable models for Cystic fibrosis (CF) precision therapy. Advances in culture techniques have improved expansion capacity of airway basal cells, while retaining functional airway epithelium physiology. However, considerable variation in response to CFTR modulators is observed even when using similar ALI culture techniques. We aimed to address if variation in response reflects true biological differences between patients or technical differences as a consequence of different culture expansion methods. Nasal epithelial brushings from 14 in iduals (CF=9 non-CF=5) were collected, then equally ided and expanded under conditional reprogramming culture (CRC) and feeder-serum-free “dual-SMAD inhibition” (SMADi) methods. Expanded cells from each culture were differentiated with proprietary PneumaCult™-ALI media. Morphology (Immunofluorescence), global proteomics (LC-MS/MS) and function (barrier integrity, cilia motility, and ion transport) were compared in CRC ALI and SMADi ALI under basal and CFTR corrector treated (VX-809) conditions. No significant difference in the structural morphology or global proteomics profile were observed. Barrier integrity and cilia motility were significantly different, despite no difference in cell junction morphology or cilia abundance. Epithelial Sodium Channels and Calcium-activated Chloride Channel activity did not differ but CFTR mediated chloride currents were significantly reduced in SMADi ALI compare to their CRC ALI counterparts. Alteration of cellular physiological function in vitro occurs were more prominent than structural and differentiation potential in airway ALI. Since culture conditions significantly influence CFTR activity, this could lead to false conclusions if data from different labs are compared against each other without specific reference ranges.
Publisher: Wiley
Date: 22-01-2020
Publisher: Wiley
Date: 24-08-2012
DOI: 10.1002/PPUL.21524
Abstract: Gastro-esophageal reflux (GOR) may contribute to lung disease in children with cystic fibrosis (CF). There is conflicting evidence regarding the effect of chest physiotherapy (CPT) in the head-down position on GOR. Furthermore, there is currently no evidence on the impact of physiotherapy on GOR as assessed by pH-multichannel intraluminal impedance (pH-MII). (1) To characterize GOR in young children with CF. (2) To determine whether the head-down position during physiotherapy exacerbates GOR. Children were studied using pH-MII monitoring over 24-hr, during which they received two 20-min sessions of CPT. One session was performed in "modified" drainage positions with no head-down tilt and the alternate session in "gravity-assisted" drainage positions, which included 20° head-down tilt. Twenty children with CF (8 males), median age 12 months (range 8-34) were recruited. A total of 1,374 reflux episodes were detected in all children, of which 869 (63%) were acid and 505 (37%) were non-acid. Seventy-two percent of the episodes migrated proximally. During CPT, there was no significant difference between total number of reflux episodes in the modified or gravity-assisted positions, median [inter-quartile range (IQR)] 1 (0-2.5) compared to 1 (0.75-3) episode, respectively, P = 0.63. There was also no significant difference between the number of reflux episodes which migrated proximally, median (IQR) 1 (0-2) compared to 0 (0-2) episodes, respectively, P = 0.75. In young children with CF, GOR is primarily acidic and proximal migration is common. Physiotherapy in the head-down position does not appear to exacerbate GOR. The impact of GOR on lung disease remains to be elucidated.
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/JPC.13680
Publisher: Elsevier BV
Date: 06-2010
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3TA02213G
Publisher: Springer Science and Business Media LLC
Date: 22-03-2023
DOI: 10.1186/S13063-023-07076-8
Abstract: Cystic fibrosis (CF) is a rare, inherited, life-limiting condition predominantly affecting the lungs, for which there is no cure. The disease is characterized by recurrent pulmonary exacerbations (PEx), which are thought to drive progressive lung damage. Management of these episodes is complex and generally involves multiple interventions targeting different aspects of disease. The emergence of innovative trials and use of Bayesian statistical methods has created renewed opportunities for studying heterogeneous populations in rare diseases. Here, we present the protocol for the BEAT CF PEx cohort, a prospective, multi-site, perpetual, platform enrolling adults and children with CF. The BEAT CF PEx cohort will be used to evaluate the comparative effectiveness of interventions for the treatment of PEx requiring intensive therapy (PERITs), with a primary focus on short-term improvements in lung function. This will be achieved through the conduct of cohort-nested studies, including adaptive clinical trials, within the BEAT CF PEx cohort. This protocol will outline key features of the BEAT CF PEx cohort, including the design, implementation, data collection and management, governance and analysis, and dissemination of results. This platform will be conducted across multiple sites, commencing with CF treatment centers in Australia. People of all ages with a clinical diagnosis of CF will be eligible to participate, except those who have previously received a lung transplant. Data including demographic and clinical information, treatment details, and outcomes (including safety, microbiology, and patient-reported outcome measures including quality of life scores) will be systematically collected and securely stored via a digital centralized trial management system (CTMS). The primary endpoint is the absolute change in the percentage predicted forced expiratory volume in 1 s (ppFEV 1 ) from the commencement of intensive therapy to 7 to 10 days afterwards. The BEAT CF PEx cohort will report clinical, treatment, and outcome data for PEx among people with CF and is intended to serve as a core (master) protocol for future nested, interventional trials evaluating treatment(s) for these episodes. The protocols for nested sub-studies are beyond the scope of this document and will be reported separately. ANZCTR BEAT CF Platform – ACTRN12621000638831. Registration date: Sept. 26, 2022.
Publisher: Authorea, Inc.
Date: 26-09-2022
Publisher: Authorea, Inc.
Date: 29-09-2022
Publisher: American Thoracic Society
Date: 15-07-2006
Publisher: Elsevier BV
Date: 03-2023
Publisher: Springer Science and Business Media LLC
Date: 25-07-2017
Publisher: Wiley
Date: 22-07-2016
DOI: 10.1111/CEA.12774
Abstract: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg.
Publisher: BMJ
Date: 07-04-2014
DOI: 10.1136/JCLINPATH-2013-201787
Abstract: Determine the prevalence of fat-soluble vitamin deficiency in children with cystic fibrosis (CF) aged ≤18 years in New South Wales (NSW), Australia, from 2007 to 2010. A retrospective analysis of fat-soluble vitamin levels in children aged ≤18 years who lived in NSW and attended any of the three paediatric CF centres from 2007 to 2010. An audit of demographic and clinical data during the first vitamin level measurement of the study period was performed. Deficiency of one or more fat-soluble vitamins was present in 240/530 children (45%) on their first vitamin level test in the study period. The prevalence of vitamins D and E deficiency fell from 22.11% in 2007 to 15.54% in 2010, and 20.22% to 13.89%, respectively. The prevalence of vitamin A deficiency increased from 11.17% to 13.13%. Low vitamin K was present in 29% in 2007, and prevalence of prolonged prothrombin time increased from 19.21% to 22.62%. Fat-soluble vitamin deficiency is present in 10%-35% of children with pancreatic insufficiency, but only a very small proportion of children who are pancreatic-sufficient. This is one of few studies of fat-soluble vitamin deficiency in children with CF in Australia. Fat-soluble vitamin testing is essential to identify deficiency in pancreatic-insufficient children who may be non-compliant to supplementation or require a higher supplement dose, and pancreatic-sufficient children who may be progressing to insufficiency. Testing of vitamin K-dependent factors needs consideration. Further studies are needed to monitor rates of vitamin deficiency in the CF community.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Informa UK Limited
Date: 03-11-2022
DOI: 10.1080/02770903.2020.1841224
Abstract: To develop and validate a prediction risk score for identification of children at risk of developing life-threatening asthma (LTA). Our study utilized existing medical records and retrospective analysis to develop and validate a risk score. The study population included children aged 2-17 years, admitted with a primary diagnosis of asthma, to Sydney Children's Hospital between 2011-2016. Children admitted in the intensive care unit with asthma at risk of LTA (cases) and those admitted into general ward (comparison group), were randomly ided into a derivation and a validation cohort. Candidate predictors from derivation cohort were selected through multivariable regression, which were used to estimate each child's risk of developing LTA in the validation cohort. Predictive performance of the risk score was evaluated by the area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test. The study population comprised of 1171 children 586 in the derivation and 585 in the validation cohort. Four independent candidate variables from derivation cohort (age at admission, socioeconomic status, a family history of asthma/atopy and previous asthma hospitalizations) were retained in the predictive model (AUROC 0.759 95% CI, 0.694-0.823), with a sensitivity of 78.5% and specificity of 46.6%. Our risk algorithm based on routinely collected clinical data may be used to develop a user-friendly risk score for early identification and monitoring of children at risk of developing LTA.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2016
Publisher: Elsevier BV
Date: 04-2015
Publisher: Springer Science and Business Media LLC
Date: 17-01-2013
DOI: 10.1007/S12529-013-9289-Y
Abstract: In children with cystic fibrosis (CF) sleep, eating/mealtime, physiotherapy adherence and internalising problems are common. Caregivers also often report elevated depression, anxiety and stress symptoms. To identify, through principal components analysis (PCA), coping strategies used by Australian caregivers of children with CF and to assess the relationship between the derived coping components, caregiver mental health symptoms and child treatment related and non-treatment related problem behaviours. One hundred and two caregivers of children aged 3 to 8 years from three CF clinic sites in Australia, completed self-report questionnaires about their coping and mental health and reported on their child's sleep, eating/mealtime, treatment adherence and internalising and externalising behaviours. Two caregiver coping components were derived from the PCA: labelled 'proactive' and 'avoidant' coping. 'Avoidant' coping correlated moderately with caregiver depression (0.52), anxiety (0.57) and stress (0.55). For each unit increase in caregiver use of avoidant coping strategies, the odds of frequent child eating/mealtime behaviour problems increased by 1.3 (adjusted 95 % CI 1.0 to 1.6, p = .03) as did the odds of children experiencing borderline/clinical internalising behaviour problems (adjusted 95 % CI 1.1 to 1.7, p = .01). Proactive coping strategies were not associated with reduced odds of any child problem behaviours. Avoidant coping strategies correlated with caregiver mental health and child problem behaviours. Intervening with caregiver coping may be a way to improve both caregiver mental health and child problem behaviours in pre-school and early school age children with CF.
Publisher: BMJ
Date: 18-10-2019
DOI: 10.1136/THORAXJNL-2018-212096
Abstract: Respiratory pathogens associated with childhood pneumonia are often detected in the upper respiratory tract of healthy children, making their contribution to pneumonia difficult to determine. We aimed to determine the contribution of common pathogens to pneumonia adjusting for rates of asymptomatic detection to inform future diagnosis, treatment and preventive strategies. A case–control study was conducted among children years in Perth, Western Australia. Cases were children hospitalised with radiologically confirmed pneumonia controls were healthy children identified from outpatient and local immunisation clinics. Nasopharyngeal swabs were collected and tested for 14 respiratory viruses and 6 bacterial species by Polymerase chain reaction (PCR). For each pathogen, adjusted odds ratio (aOR 95% CI) was calculated using multivariate logistic regression and population-attributable fraction (95% CI) for pneumonia was estimated. From May 2015 to October 2017, 230 cases and 230 controls were enrolled. At least one respiratory virus was identified in 57% of cases and 29% of controls (aOR: 4.7 95% CI: 2.8 to 7.8). At least one bacterial species was detected in 72% of cases and 80% of controls (aOR: 0.7 95% CI: 0.4 to 1.2). Respiratory syncytial virus (RSV) detection was most strongly associated with pneumonia (aOR: 58.4 95% CI: 15.6 to 217.5). Mycoplasma pneumoniae was the only bacteria associated with pneumonia (aOR: 14.5 95% CI: 2.2 to 94.8). We estimated that RSV, human metapneumovirus (HMPV), influenza, adenovirus and Mycoplasma pneumoniae were responsible for 20.2% (95% CI: 14.6 to 25.5), 9.8% (5.6% to 13.7%), 6.2% (2.5% to 9.7%), 4% (1.1% to 7.1%) and 7.2% (3.5% to 10.8%) of hospitalisations for childhood pneumonia, respectively. Respiratory viruses, particularly RSV and HMPV, are major contributors to pneumonia in Australian children.
Publisher: BMJ
Date: 11-2017
DOI: 10.1136/BMJOPEN-2017-017936
Abstract: To determine the contribution of respiratory syncytial virus (RSV) to the subsequent development of severe asthma in different subgroups of children at risk of severe RSV disease. The study was conducted in New South Wales (NSW), Australia. The study comprised all children born in NSW between 2000 and 2010 with complete follow-up till 31 December 2011. The cohort was ided into three subgroups: (1) non-Indigenous high-risk children: non-Indigenous children born preterm or born with a low birth weight (2) Indigenous children: children of mothers whose Indigenous status was recorded as Aboriginal and/or Torres Strait Islander and (3) non-Indigenous standard risk children: all other non-Indigenous term children. Risk of development of severe asthma in different subgroups of children who had RSV hospitalisation in the first 2 years of life compared with those who did not. We performed a retrospective cohort analysis using population-based linked administrative data. Extended Cox model was used to determine HR and 95% CI around the HR for first asthma hospitalisation in different subgroups of children. The cohort comprised 847 516 children born between 2000 and 2010. In the adjusted Cox model, the HR of first asthma hospitalisation was higher and comparable across all subgroups of children who had RSV hospitalisation compared with those who did not. The HR (95% CI) was highest in children aged 2–3 years 4.3 (95% CI 3.8 to 4.9) for high-risk, 4.0 (95% CI 3.3 to 4.8) for Indigenous and 3.9 (95% CI 3.7 to 4.1) for non-Indigenous standard risk children. This risk persisted beyond 7 years of age. This large study confirms a comparable increased risk of first asthma hospitalisation following RSV disease in the first 2 years of life across different subgroups children at risk.
Publisher: Elsevier BV
Date: 03-1999
DOI: 10.1016/S0140-6736(98)06532-5
Abstract: We and others have previously reported significant changes in chloride transport after cationic-lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the nasal epithelium of patients with cystic fibrosis. We studied the safety and efficacy of this gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial. Eight patients with cystic fibrosis were randomly assigned DNA-lipid complex (active) by nebulisation into the lungs followed 1 week later by administration to the nose. Eight control patients followed the same protocol but with the lipid alone (placebo). Safety was assessed clinically, by radiography, by pulmonary function, by induced sputum, and by histological analysis. Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA, in-vivo potential difference, epifluorescence assay of chloride efflux, and bacterial adherence. Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patients in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration. No specific treatment was required for either event. Pulmonary administration resulted in a significant (p<0.05) degree of correction of the chloride abnormality in the patients receiving active treatment but not in those on placebo when assessed by in-vivo potential difference and chloride efflux. Bacterial adherence was also reduced. We detected no alterations in the sodium transport abnormality. A similar pattern occurred following nasal administration. Cationic-lipid-mediated CFTR gene transfer can significantly influence the underlying chloride defect in the lungs of patients with cystic fibrosis.
Publisher: Elsevier BV
Date: 03-2008
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.BRAT.2017.08.010
Abstract: Anxiety disorders are highly prevalent in children with asthma yet very little is known about the parenting factors that may underlie this relationship. The aim of the current study was to examine observed parenting behaviours - involvement and negativity - associated with asthma and anxiety in children using the tangram task and the Five Minute Speech S le (FMSS). Eighty-nine parent-child dyads were included across four groups of children (8-13 years old): asthma and anxiety, anxiety only, asthma only and healthy controls. Overall, results from both tasks showed that parenting behaviours of children with and without asthma did not differ significantly. Results from a subcomponent of the FMSS indicated that parents of children with asthma were more overprotective, or self-sacrificing, or non-objective than parents of children without asthma, and this difference was greater in the non-anxious groups. The results suggest that some parenting strategies developed for parents of children with anxiety may be useful for parents of children with asthma and anxiety (e.g. strategies targeting involvement), however, others may not be necessary (e.g. those targeting negativity).
Publisher: Springer Science and Business Media LLC
Date: 08-2005
Publisher: Elsevier BV
Date: 06-2013
Publisher: Springer Science and Business Media LLC
Date: 13-01-2020
DOI: 10.1186/S12887-020-1911-Y
Abstract: Fever in childhood is a common acute presentation requiring clinical triage to identify the few children who have serious underlying infection. Clinical practice guidelines (CPGs) have been developed to assist clinicians with this task. This study aimed to assess the proportion of care provided in accordance with CPG recommendations for the management of fever in Australian children. Clinical recommendations were extracted from five CPGs and formulated into 47 clinical indicators for use in auditing adherence. Indicators were categorised by phase of care: assessment, diagnosis and treatment. Patient records from children aged 0 to 15 years were s led from general practices (GP), emergency departments (ED) and hospital admissions in randomly-selected health districts in Queensland, New South Wales and South Australia during 2012 and 2013. Paediatric nurses, trained to assess eligibility for indicator assessment and adherence, reviewed eligible medical records. Adherence was estimated by in idual indicator, phase of care, age-group and setting. The field team conducted 14,879 eligible indicator assessments for 708 visits by 550 children with fever in 58 GP, 34 ED and 28 hospital inpatient settings. For the 33 indicators with sufficient data, adherence ranged from 14.7 to 98.1%. Estimated adherence with assessment-related indicators was 51.3% (95% CI: 48.1–54.6), 77.5% (95% CI: 65.3–87.1) for diagnostic-related indicators and 72.7% (95% CI: 65.3–79.3) for treatment-related indicators. Adherence for children 3 months of age was 73.4% (95% CI: 58.0–85.8) and 64.7% (95% CI: 57.0–71.9) for children 3–11 months of age, both significantly higher than for children aged 4–15 years (53.5% 95% CI: 50.0–56.9). The proportion of adherent care for children attending an ED was 77.5% (95% CI: 74.2–80.6) and 76.7% (95% CI: 71.7–81.3) for children admitted to hospital, both significantly higher than for children attending a GP (40.3% 95% CI: 34.6–46.1). This study reports a wide range of adherence by clinicians to 47 indicators of best practice for the management of febrile children, s led from urban and rural regions containing 60% of the Australian paediatric population. Documented adherence was lowest for indicators related to patient assessment, for care provided in GP settings, and for children aged 4–15 years.
Publisher: American Academy of Pediatrics (AAP)
Date: 02-2012
Abstract: National data registries for cystic fibrosis (CF) enable comparison of health statistics between countries. We examined the US and Australian CF data registries to compare demographics, clinical practice and outcome measures. We compared the 2003 US and Australian registries. Differences in pulmonary and growth outcomes were assessed by creating models controlling for differences in age, gender, genotype, and diagnosis after newborn screening. Data on 12 994 US and 1220 Australian patients aged ≤18 years were analyzed. A significant difference was noted in the proportion who had been diagnosed after newborn screening (Australian 65.8% vs United States 7.2% P & .001). Australian children had significantly greater mean height percentile (41.0 vs 32.6 P & .001) and weight percentile (43.5 vs 36.1 P = .028) than US children. Mean forced expiratory volume in 1 second (FEV1) percent predicted adjusted for age, gender, and genotype was similar in the 2 countries (P = .80). Patients diagnosed after newborn screening had higher mean FEV1 (5.3 [95% confidence interval (CI): 3.6–7.0]) percent predicted and BMI (0.26 [95% CI: 0.09–0.43]). Mean FEV1 of Australian patients diagnosed after newborn screening was lower by 5.2 (95% CI: 2.8–7.6) percent predicted compared with US children. Children diagnosed with CF after newborn screening benefited from better lung function and BMI than those diagnosed clinically. The benefit of newborn screening on lung function was significantly less in Australian children compared with US children. Statistical comparisons between CF registries are feasible and can contribute to benchmarking and improvements in care.
Publisher: European Respiratory Society (ERS)
Date: 02-2004
Publisher: Cambridge University Press (CUP)
Date: 08-2009
DOI: 10.1017/S0965539509990052
Abstract: Congenital cystic adenomatoid malformations of the lung (CCAMs) were originally described by Ch'In and Tang in 1949 as rare lung lesions occurring in premature or stillborn infants with anasarca. In 1977 Stocker et al ided CCAM into three types based on their clinical and pathological features. The nomenclature has since changed to congenital pulmonary airway malformations (CPAMs) to reflect the possible absence of cystic changes and the probable underlying pathogenesis of different types. CPAMs are relatively rare congenital abnormalities with a reported incidence varying from 1 in 10,000 to 1 in 35,000. There is a slight male predominance, but no racial predilection has been noted. This review will outline the current nomenclature and features of different types of CPAMs, highlight possible mechanisms underlying the development of CPAMs, review current antenatal imaging modalities and interventions, address the debate surrounding the postnatal management of CPAMs, and suggest areas for future research.
Publisher: BMJ
Date: 18-05-2012
DOI: 10.1136/ARCHDISCHILD-2011-301527
Abstract: In cystic fibrosis (CF), problems with sleep, eating/mealtime behaviours, physiotherapy adherence and parental mental health issues are common, yet their natural history and the extent of service use to address them are unknown. Follow up the 2007 cohort to determine: (1) prevalence of child sleep, eating/mealtime behaviours, physiotherapy adherence, and externalising/internalising problem behaviours and primary caregiver mental health status after a 3-year period (2) natural history of child behaviours (3) potentially modifiable predictors of persistent problems and (4) service use for behaviours. Prospective cohort. Setting: Royal Children's Hospital, Monash Medical Centre and Sydney Children's Hospital (Australia) CF clinics. Caregivers, of children aged 3–8 years, who completed the baseline questionnaire. Child sleep, eating/mealtime behaviours, adherence with therapy and externalising and internalising behaviours. Predictors: parenting style (low warmth), caregiver mental health status and sleep quality at baseline. 102 of 116 (88%) families participated. The prevalence of sleep and eating/mealtime problems at follow-up was similar to baseline. The prevalence of caregiver mental health symptoms remained higher than the community data. 71 out of 102 (70%) of the children experienced at least one persistent behaviour problem. Caregiver mental health difficulties predicted persistent child moderate to severe sleep problems (adjusted OR 6.5, 95% CI 1.2 to 36.2, p=0.03) and their persistently poor adherence to the physiotherapy regimen (adjusted OR 3.5, 95% CI 1.3 to 9.2, p=0.01). Child problem behaviours are common in children with CF, persist and are often predicted by the mental health of the parent. Routine surveillance for and management of child problem behaviours are recommended.
Publisher: Oxford University Press (OUP)
Date: 07-2009
DOI: 10.1111/J.1365-2230.2008.03142.X
Abstract: Children with atopic eczema (AE) are at risk of developing asthma. Airway inflammation has been shown to be present before the onset of clinical asthma. Increased exhalation (forced expiration FE) of nitric oxide (FE(NO)) and 8-isoprostane seems to be a feature of bronchial inflammation in people with asthma. To determine whether the exhalation of these two molecules is increased in children with eczema, even in the absence of overt asthma. In total, 21 children with AE were recruited and compared with healthy controls. A questionnaire was completed to identify respiratory symptoms compatible with asthma. The severity of AE was graded clinically. Spirometry, FE(NO) measurements and exhaled breath condensate collection for 8-isoprostane were performed. The mean level of 8-isoprostane was similar for children with AE (2.33 +/- 4.76 pg/mL) and controls (3.37 +/- 3.43). FE(NO) was increased in children with AE (mean 64.97 parts per billion) compared with the normal range, even in the absence of respiratory symptoms and in the presence of normal lung function. FE(NO) but not 8-isoprostane levels in exhaled breath condensate are higher in children with AE without asthma. Our finding may indicate a predictive role for FE(NO) for the development of asthma.
Publisher: BMJ
Date: 03-1999
DOI: 10.1136/ADC.80.3.286
Publisher: Wiley
Date: 14-02-2023
DOI: 10.1002/PPUL.26324
Abstract: Uniformity and compliance with clinical practice guidelines (CPGs) for use of palivizumab in preventing severe respiratory syncytial viral infection in Australian high‐risk infants remain unclear. An online survey was conducted across the Australian and New Zealand Neonatal Network (ANZNN) to determine clinical practices around palivizumab. A literature search was also performed to identify and compare national and international guidelines. A total of 65 of 422 ANZNN members completed the survey. Respondents included 61 senior medical staff of consultants/staff specialists (78%) and four nursing staff (6%). According to the survey, infants most likely to be recommended palivizumab included preterm infants born weeks gestational age (GA) (30%), children with chronic lung diseases (CLDs) born weeks GA (40%), and with hemodynamically significant heart disease (35%). Many of the respondents (53%) stated that CPGs for palivizumab were developed locally. Literature search identified 20 guidelines (10 international and 10 domestic) 16 (80%) recommended palivizumab use in preterm infants, 16 (80%) recommended use in infants with CLD, 17 (85%) in congenital heart disease and 6 (30%) in bronchopulmonary dysplasia (BPD). Eight (40%) guidelines provided specific recommendations for immunocompromised infants. Canada, Western Australia, and American Academy of Paediatrics provided recommendations for Indigenous children. Frequency and dosage of palivizumab was universal across all CPGs. None of the international guidelines obtained were from low‐ or middle‐income countries. Standardization of CPGs may improve clinical decision making around use of palivizumab in high‐risk infants.
Publisher: Massachusetts Medical Society
Date: 09-2016
Publisher: BMJ
Date: 25-05-2019
DOI: 10.1136/ARCHDISCHILD-2017-314241
Abstract: Oropharyngeal suction and oropharyngeal swab are two methods of obtaining airway s les with similar diagnostic accuracy in children with cystic fibrosis (CF). The primary aim was comparing distress between suctioning and swabbing. A secondary aim was establishing the reliability of the Groningen Distress Rating Scale (GDRS). Randomised oropharyngeal suction or swab occurred over two visits. Two physiotherapists and the child’s parent rated distress using the GDRS. Heart rate (HR) was also measured. 24 children with CF, mean age of 3 years, participated. Both physiotherapist and parent rating showed significantly higher distress levels during suction than swab. Inter-rater reliability for the GDRS was very good between physiotherapists, and good between physiotherapist and parents. The study found that oropharyngeal swab is less distressing in obtaining s les than oropharyngeal suction and that the GDRS was reliable and valid.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2014
Publisher: Oxford University Press (OUP)
Date: 28-10-2019
Abstract: To determine the extent to which care received by Australian children presenting with croup is in agreement with Clinical Practice Guidelines (CPGs). Retrospective population-based s le survey. Croup clinical indicators were derived from CPGs. Medical records from three healthcare settings were s led for selected visits in 2012 and 2013 in three Australian states. Data were collected by nine experienced paediatric nurses, trained to assess eligibility for indicator assessment and adherence to CPGs. Surveyors undertook criterion-based medical record reviews using an electronic data collection tool. Documented guideline adherence was lower for general practitioners (65.9% 95% CI: 60.8–70.6) than emergency departments (91.1% 95% CI: 89.5–92.5) and inpatient admissions (91.3% 95% CI: 88.1–93.9). Overall adherence was very low for a bundle of 10 indicators related to assessment (4.5% 95% CI: 2.4–7.6) but higher for a bundle of four indicators relating to the avoidance of inappropriate therapy (83.1% 95% CI: 59.5–96.0). Most visits for croup were characterized by appropriate treatment in all healthcare settings. However, most children had limited documented clinical assessments, and some had unnecessary tests or inappropriate therapy, which has potential quality and cost implications. Universal CPG and clinical assessment tools may increase clinical consistency.
Publisher: Informa UK Limited
Date: 07-2018
DOI: 10.1017/EDP.2018.3
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3SC03828A
Publisher: Springer Science and Business Media LLC
Date: 09-01-2017
DOI: 10.1007/S10802-017-0261-1
Abstract: Children with asthma have a high prevalence of anxiety disorders, however, very little is known about the mechanisms that confer vulnerability for anxiety in this population. This study investigated whether children with asthma and anxiety disorders display attentional biases towards threatening stimuli, similar to what has been seen in children with anxiety disorders more generally. We also examined the relationships between attentional biases and anxiety symptomatology and asthma control for children with asthma. Ninety-three children, aged 8-13, took part in the study and were recruited into one of four conditions (asthma/anxiety, asthma, anxiety, control). Asthma was medically confirmed and anxiety was assessed through clinical interview. We used self- and parent-report questionnaires to measure child asthma (ATAQ) and anxiety (SCAS, CASI) variables. Participants completed a visual dot-probe task designed to measure attentional bias towards two types of stimuli: asthma related words and general threat words, as well as tasks to assess reading ability and attentional control. Results showed that attentional biases did not differ between the groups, although children with anxiety disorders displayed poorer attentional control. A significant correlation was found between poor asthma control and an attentional bias of asthma stimuli. While we found no evidence that anxiety disorders in children with asthma were associated with threat- or asthma-related attentional biases, preliminary evidence suggested that children with poor asthma control displayed biases towards asthma-specific stimuli. Future research is needed to explore whether these attentional biases are adaptive.
Publisher: Wiley
Date: 06-2001
DOI: 10.1002/PPUL.1076
Publisher: Elsevier BV
Date: 03-2021
DOI: 10.1016/J.JCF.2020.12.019
Abstract: Patient-derived airway cells differentiated at Air Liquid Interface (ALI) are valuable models for Cystic fibrosis (CF) precision therapy. Different culture expansion methods have been established to extend expansion capacity of airway basal cells, while retaining functional airway epithelium physiology. Considerable variation in response to CFTR modulators is observed in cultures even within the same CFTR genotype and despite the use of similar ALI culture techniques. We aimed to address culture expansion method impact on differentiation. Nasal epithelial brushings from 14 in iduals (CF=9 non-CF=5) were collected, then equally ided and expanded under conditional reprogramming culture (CRC) and feeder-serum-free "dual-SMAD inhibition" (SMADi) methods. Expanded cells from each culture were differentiated with proprietary PneumaCult™-ALI media. Morphology (Immunofluorescence), global proteomics (LC-MS/MS) and function (barrier integrity, cilia motility, and ion transport) were compared in CRC No significant difference in the structural morphology or baseline global proteomics profile were observed. Barrier integrity and cilia motility were significantly different, despite no difference in cell junction morphology or cilia abundance. Epithelial Sodium Channels and Calcium-activated Chloride Channel activity did not differ but CFTR mediated chloride currents were significantly reduced in SMADi Alteration of cellular physiological function in vitro were more prominent than structural and differentiation potential in airway ALI. Since initial expansion culture conditions significantly influence CFTR activity, this could lead to false conclusions if data from different labs are compared against each other without specific reference ranges.
Publisher: Frontiers Media SA
Date: 07-12-2018
Publisher: Wiley
Date: 07-2009
DOI: 10.1111/J.1440-1754.2009.01533.X
Abstract: Aims: To investigate the change in incidence of childhood empyema and pneumonia in Australia, and ascertain the management trends in all hospitals caring for children with empyema. Methods: The incidences of empyema and pneumonia were calculated for each year between 1993/1994 and 2004/2005 using retrospective primary diagnostic coding from ICD‐9 and 10 comprising the Australian National Hospital Morbidity Database for five age groups in patients less than 20 years of age. Hospitals with allocated paediatric beds were surveyed on referral pattern and treatment preferences. Results: In this study, 145 562 patients with pneumonia were admitted with a mean (range) incidence of 2306 (1846–2652) per million. The trend towards an overall increase was not statistically significant. Only the 1–4 years old age group demonstrated a significant increase ( P 0.01, r 2 = 0.61). A total of 469 cases of empyema were identified with a mean incidence of 7.35 (4–10.2) per million. There was an overall increase in incidence ( P 0.05, r 2 = 0.51) reflecting an increase in the 1‐ to 4‐year‐olds ( P 0.005, r 2 = 0.60) and 15‐ to 19‐year‐olds ( P 0.05, r 2 = 0.37). The overall percentage of empyema as a proportion of pneumonia increased from 0.27 to 0.70% (0.48% (0.27–0.70%), P 0.05, r 2 = 0.38). The survey response rate was 75%. Ninety‐nine of 121 (82%) hospitals referred children with empyema to a more appropriate centre with wide variations in treatments provided. Conclusions: The rise in incidence of empyema reflects that seen in other countries. Furthermore, there are erse management practices suggesting a clear need for national guidelines.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Springer Science and Business Media LLC
Date: 20-12-2022
DOI: 10.1038/S41598-022-26492-5
Abstract: Mass community testing is a critical means for monitoring the spread of the COVID-19 pandemic. Polymerase chain reaction (PCR) is the gold standard for detecting the causative coronavirus 2 (SARS-CoV-2) but the test is invasive, test centers may not be readily available, and the wait for laboratory results can take several days. Various machine learning based alternatives to PCR screening for SARS-CoV-2 have been proposed, including cough sound analysis. Cough classification models appear to be a robust means to predict infective status, but collecting reliable PCR confirmed data for their development is challenging and recent work using unverified crowdsourced data is seen as a viable alternative. In this study, we report experiments that assess cough classification models trained (i) using data from PCR-confirmed COVID subjects and (ii) using data of in iduals self-reporting their infective status. We compare performance using PCR-confirmed data. Models trained on PCR-confirmed data perform better than those trained on patient-reported data. Models using PCR-confirmed data also exploit more stable predictive features and converge faster. Crowd-sourced cough data is less reliable than PCR-confirmed data for developing predictive models for COVID-19, and raises concerns about the utility of patient reported outcome data in developing other clinical predictive models when better gold-standard data are available.
Publisher: Elsevier BV
Date: 06-2017
Publisher: Wiley
Date: 19-10-2007
Publisher: BMJ
Date: 11-2005
Publisher: Elsevier BV
Date: 06-2003
Publisher: Elsevier BV
Date: 05-2023
Publisher: Springer Science and Business Media LLC
Date: 02-2000
Abstract: Gene therapy in patients with cystic fibrosis may need to be commenced before the onset of lung disease which may be evident as early as 4 weeks after birth. We assessed the efficacy of cationic lipid-mediated transfer of a reporter gene, chlor henicol acetyltransferase, in the growing murine and human respiratory tract. Gene expression was greater in adult mice (greater than 8 weeks old) compared with 9- and 16-day-old animals, despite a relatively greater proportion of complex delivered to the younger mice. Subsequent experiments compared 16-day-old and adult mice. Whilst higher gene expression occurred in the parenchyma compared with conducting airways in both groups, significantly greater expression was seen in the conducting airway of adult mice compared with 16-day-old animals. This expression persisted beyond 18 days in the adults but was undetectable in the younger group at this time-point. In an ex vivo model there was no difference in gene expression between the two groups. Further, no differences were observed in gene expression between growing (age 5 weeks to 14 years 8 months) and adult human lung tissue in either parenchyma or conducting airway. These data suggest age-dependent differences in gene transfer in vivo, which are not seen in an ex vivo setting. Proof-of-principle has been demonstrated for cationic-lipid mediated gene transfer to the growing human lung. Gene Therapy (2000) 7, 273-278.
Publisher: Frontiers Media SA
Date: 16-03-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2009
Publisher: Elsevier BV
Date: 09-2001
Abstract: Epidemiological studies have suggested that many rare diseases with respiratory involvement have a genetic component. Molecular advances have increased the understanding of the pathophysiology of these diseases which has led to better diagnostic and prognostic methods. There may be many genes responsible for diseases such as primary ciliary dyskinesia and systemic lupus erythematosus in addition to the effect of modifier genes. The genotype:phenotype correlation in these diseases remains to be elucidated. In some diseases, such as familial dysautonomia and sickle cell, the gene has been identified which allows for accurate pre-natal testing. Further, in diseases where the genetic abnormality is known, such as chronic granulomatous disease, gene therapy remains a realistic prospect and phase I studies are about to commence or currently underway. This article reviews those rare diseases in which there is or is likely to be a significant genetic contribution.
Publisher: BMJ
Date: 11-03-2022
DOI: 10.1136/ARCHDISCHILD-2021-322536
Abstract: To investigate the validity and home use of a personal ultrasonic spirometer. Supervised spirometry was performed using laboratory equipment and a personal ultrasonic spirometer. In addition, the ability of children to perform acceptable spirometry during supervised telehealth appointments at home was assessed. 59 children completed spirometry on both devices. There was high between-device intraclass correlation coefficient (ICC) for forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC): ICC 0.991 (95% CI 0.985 to 0.995) and 0.989 (95% CI 0.981 to 0.993), respectively. Bland-Altman analysis revealed mean bias and limits of agreement of −0.01 (−0.22 to 0.24) L for FEV 1 and −0.02 (−0.30 to 0.33) L for FVC. 125 of 140 (89%) supervised telehealth spirometry sessions were acceptable. There was excellent reliability in between-device measurements however, the limits of agreement were wide. Therefore, caution is needed if the device is used interchangeably with laboratory equipment. High success rates of telehealth spirometry sessions indicate the device is suitable for this application.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.PRRV.2007.05.002
Abstract: Empyema is an important cause of childhood morbidity with an increasing worldwide incidence. Despite many treatment options being available, there is no general consensus on the optimal management approach due to conflicting reports and lack of properly conducted studies to challenge the personal bias of a physician or surgeon. The reason for this is likely to be the fact that, irrespective of the treatment children receive, they ultimately make an excellent clinical recovery. This review summarises the current evidence and evaluates the clinical efficacy of various treatment modalities in the context of relevant outcome measures in an attempt to demonstrate the differences in treatment options for the child with empyema.
Publisher: Wiley
Date: 13-11-2014
DOI: 10.1111/JPC.12775
Publisher: AMPCo
Date: 07-2011
Publisher: European Respiratory Society (ERS)
Date: 07-2005
DOI: 10.1183/09031936.05.00127704
Abstract: The aim of the current study was to review the aetiology of non-cystic fibrosis (CF) bronchiectasis from two tertiary paediatric respiratory units in order to determine how often making a specific aetiological diagnosis leads to a change in management, and to assess the contribution of computed tomography (CT) in determining the underlying diagnosis. The case records of all patients who were diagnosed as having bronchiectasis by CT, currently being seen at the Royal Brompton Hospital and Great Ormond Street Hospital for Children (London, UK), were reviewed. All patients had undergone extensive investigations, and the underlying aetiology and the area of pulmonary involvement (as seen on CT) were recorded. A total of 136 patients were identified there were 65 young males and the group median (range) age was 12.1 yrs (3.1-18.1). Immunodeficiency, aspiration and primary ciliary dyskinesia accounted for 67% of the cases. In 77 (56%) children, the identification of a cause led to a specific change in management. There was no association between aetiology and the distribution of CT abnormalities. In conclusion, immunodeficiency and other intrinsic abnormalities account for the majority of cases of non-cystic fibrosis bronchiectasis seen in the current authors' units. Computed tomography scans do not contribute towards identifying the aetiology and, most importantly, a specific aetiological diagnosis frequently leads to a change in management.
Publisher: MDPI AG
Date: 28-09-2020
DOI: 10.3390/NU12102964
Abstract: Evidence for diet quality representing a modifiable risk factor for age-related cognitive decline and mood disturbances has typically come from retrospective, cross-sectional analyses. Here a diet screening tool (DST) was used to categorize healthy middle-aged volunteers (n = 141, 40–65 years) into “optimal” or “sub-optimal” diet groups to investigate cross-sectional associations between diet quality, cognitive function, and mood. The DST distinguished levels of nutrient intake as assessed by Automated Self-Administered 24-h dietary recall and nutrient status, as assessed by blood biomarker measures. Compared with the “sub-optimal” group, the “optimal” diet group showed significantly higher intake of vitamin E (p = 0.007), magnesium (p = 0.001), zinc (p = 0.043) and fiber (p = 0.015), higher circulating levels of vitamin B6 (p = 0.030) and red blood cell folate (p = 0.026) and lower saturated fatty acids (p = 0.012). Regarding psychological outcomes, the “optimal” diet group had significantly better Stroop processing than those with a “sub-optimal” diet (p = 0.013). Regression analysis revealed that higher DST scores were associated with fewer mood disturbances (p = 0.002) and lower perceived stress (p = 0.031), although these differences were not significant when comparing “optimal” versus “sub-optimal” as discrete groups. This study demonstrates the potential of a 20-item diet screen to identify both nutritional and psychological status in an Australian setting.
Publisher: SAGE Publications
Date: 05-2012
Publisher: BMJ
Date: 23-12-2017
Publisher: Elsevier BV
Date: 11-2023
Publisher: BMJ
Date: 2003
Publisher: Elsevier BV
Date: 06-2018
Publisher: Informa UK Limited
Date: 13-06-2016
DOI: 10.1080/17476348.2016.1190646
Abstract: Cystic fibrosis-related diabetes (CFRD) is the end-point of a spectrum of glucose abnormalities in cystic fibrosis that begins with early insulin deficiency and ultimately results in accelerated nutritional decline and loss of lung function. Current diagnostic and management regimens are unable to entirely reverse this clinical decline. This review summarises the current understanding of the pathophysiology of CFRD, the issues associated with using oral glucose tolerance tests in CF and the challenges faced in making the diagnosis of CFRD. Medline database searches were conducted using search terms "Cystic Fibrosis Related Diabetes", "Cystic Fibrosis" AND "glucose", "Cystic Fibrosis" AND "insulin", "Cystic Fibrosis" AND "Diabetes". Additionally, reference lists were studied. Expert commentary: Increasing evidence points to early glucose abnormalities being clinically relevant in cystic fibrosis and as such novel diagnostic methods such as continuous glucose monitoring or 30 minute s led oral glucose tolerance test (OGTT) may play a key role in the future in the screening and diagnosis of early glucose abnormalities in CF.
Publisher: BMJ
Date: 10-2007
Publisher: Elsevier BV
Date: 07-2021
Publisher: European Respiratory Society (ERS)
Date: 12-2018
Publisher: American Chemical Society (ACS)
Date: 07-11-2022
DOI: 10.1021/JACS.2C08607
Publisher: Public Library of Science (PLoS)
Date: 07-11-2019
Publisher: Wiley
Date: 11-2008
Publisher: European Respiratory Society (ERS)
Date: 21-06-2023
DOI: 10.1183/13993003.00960-2021
Abstract: In people with cystic fibrosis (CF), regular nebulisation of 6% or 7% saline improves lung function however, these concentrations are not always tolerable. Clinically, some CF patients report using lower concentrations of saline to improve tolerability, yet the effects of lower concentrations are unknown. This study therefore aimed to evaluate the relative effectiveness and tolerability of 0.9% versus 3% versus 6% saline nebulised twice daily with an eFlow rapid nebuliser. This was a randomised, blinded, placebo-controlled, parallel-group, multicentre study where subjects inhaled 4 mL of 0.9%, 3% or 6% saline twice daily for 16 weeks. The primary outcome was forced expiratory volume in 1 s. The secondary outcomes were: forced vital capacity (FVC) and forced expiratory flow at 25–75% of FVC quality of life exercise capacity acquisition or loss of bacterial organisms in expectorated sputum tolerability of nebulised saline pulmonary exacerbations and adverse events. 140 participants were randomised to 0.9% (n=47), 3% (n=48) or 6% (n=45) saline. 134 participants (96%) contributed to the intention-to-treat analysis. 3% saline significantly improved lung function and increased the time to first pulmonary exacerbation compared with 0.9% saline but did not improve quality of life. 6% saline had similar benefits to 3% saline but also significantly improved quality of life compared with 3% saline. Only 6% saline delayed the time to intravenous antibiotics for pulmonary exacerbation. Tolerability and adherence were similar. Dilution of 6% saline to 3% maintains the benefits for lung function and exacerbation prevention however, the positive impacts of 6% saline on quality of life and time to i.v. antibiotics for pulmonary exacerbations are lost.
Publisher: Public Library of Science (PLoS)
Date: 09-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2015
Publisher: Elsevier BV
Date: 2021
Publisher: European Respiratory Society
Date: 09-2016
Publisher: BMJ
Date: 14-04-2012
Abstract: The aim of this study was to determine if once daily insulin detemir reverses decline in weight and lung function in patients with cystic fibrosis (CF). 12 patients with early insulin deficiency and six with CF related diabetes (aged 7.2-18.1 years) were treated for a median of 0.8 years. Changes in weight and lung function following treatment were compared to pretreatment changes. Before treatment, the change in weight SD score (ΔWtSDS), percentage of predicted forced expiratory volume in 1 s (Δ%FEV(1)) and percentage of predicted forced vital capacity (Δ%FVC) declined in the whole study population (-0.45±0.38, -7.9±12.8%, -5.8±14.3%) and in the subgroup with early insulin deficiency (-0.41±0.43, -9.8±9.3%, -6.8±10.3%). Following treatment with insulin ΔWtSDS, Δ%FEV(1) and Δ%FVC significantly improved in the whole study population (+0.18±0.29 SDS, p=0.0001 +3.7±10.6%, p=0.007 +5.2±12.7%, p=0.013) and in patients with early insulin deficiency (+0.22±0.31 SDS, p=0.003 +5.3±11.5%, p=0.004 +5.8±13.4%, p=0.024). Randomised controlled trials are now needed.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2SC03577D
Publisher: BMJ
Date: 11-2005
Publisher: Elsevier BV
Date: 02-1998
DOI: 10.1016/S0140-6736(05)78360-4
Abstract: Antimicrobial resistance remains a major global public health concern, and antimicrobial dispensing in community pharmacies is an important factor in preventing this damage. However, the current literature focuses on the technical and attitudinal aspects related to antimicrobial dispensing, with little emphasis on the interventions provided in this service. Thus, this study aimed to determine the antimicrobial dispensing process in community pharmacies. A scoping review was performed in September 2020 using the PubMed, EMBASE, LILACS, Web of Science, and Cochrane databases. The search terms included words related to dispensing, antibacterial agents, and pharmacies in various combinations. Two reviewers screened the titles, abstracts, and full-text articles according to the eligibility criteria, and extracted the data. The findings were presented in a descriptive form. Of the 7713 studies screened, 35 were included, of which 22 (63%) were published in Asia. Most studies followed a cross-sectional design (n = 27), and the simulated patient was the most often used method to assess the antimicrobial dispensing process (n = 22). Moreover, 31 (89%) studies investigated antimicrobial dispensing without prescription, and only four (11%) studies evaluated antimicrobial dispensing with prescription. In the 35 studies, the most frequently asked questions were about drug allergies (n = 19) and patient symptoms (n = 18), and counseling mainly focused on the side effects (n = 14), precautions (n = 14), how to take the medication (n = 12), and duration of medication use (n = 11). Another common intervention was referral (n = 15). Among clinical cases, counseling on medication use occurred often in cases of urinary tract infection (51%) and otitis media (50%). Antimicrobial dispensing processes have been primarily investigated in low- and middle-income countries, with a focus on dispensing antimicrobials without prescriptions. During the dispensing process, pharmacists mostly posed minimal questions and counseling, highlighting the deficiencies that persist in this practice. Our results indicate the need for multifaceted strategies, such as implementing educational, regulatory or administrative strategies and changes in cultural background, especially in low- and middle-income countries, that aim to reduce indiscriminate use of antimicrobials. Therefore, qualifying the antimicrobial dispensing process is a fundamental factor for improving the rational use of antimicrobials and reducing microbial resistance.
Publisher: American Academy of Pediatrics (AAP)
Date: 27-01-2022
Abstract: COVID-19 public health measures altered respiratory syncytial virus (RSV) epidemiology. We examined age-stratified trends in RSV-related disease in Australian children in 2020 compared with previous years.
Publisher: Authorea, Inc.
Date: 02-11-2022
DOI: 10.22541/AU.166740302.29601419/V1
Abstract: Addressing the recognised challenges and inequalities in providing high quality health care 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, realised, and transferred within such collaborative clinical and research networks. The community of clinical practice formed in the chILDRANZ multidisciplinary clinical peer support 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 expert clinical networks for rare disease.
Publisher: Birkhäuser-Verlag
Date: 2005
Publisher: European Respiratory Society (ERS)
Date: 09-08-2013
DOI: 10.1183/09031936.00060512
Abstract: Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In Australia, there is only limited evidence of unrelated patients sharing indistinguishable P. aeruginosa strains. We therefore examined the point-prevalence, distribution, ersity and clinical impact of P. aeruginosa strains in Australian CF patients nationally. 983 patients attending 18 Australian CF centres provided 2887 sputum P. aeruginosa isolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant. Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres, respectively. AUST-01 was associated with significantly greater treatment requirements than unique P. aeruginosa strains. Multiple clusters of shared P. aeruginosa strains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation. Longitudinal studies are now needed to determine the infection control implications of these findings.
Publisher: MDPI AG
Date: 30-03-2023
DOI: 10.3390/IJMS24076475
Abstract: Localized and chronic hypoxia of airway mucosa is a common feature of progressive respiratory diseases, including cystic fibrosis (CF). However, the impact of prolonged hypoxia on airway stem cell function and differentiated epithelium is not well elucidated. Acute hypoxia alters the transcription and translation of many genes, including the CF transmembrane conductance regulator (CFTR). CFTR-targeted therapies (modulators) have not been investigated in vitro under chronic hypoxic conditions found in CF airways in vivo. Nasal epithelial cells (hNECs) derived from eight CF and three non-CF participants were expanded and differentiated at the air–liquid interface (26–30 days) at ambient and 2% oxygen tension (hypoxia). Morphology, global proteomics (LC-MS/MS) and function (barrier integrity, cilia motility and ion transport) of basal stem cells and differentiated cultures were assessed. hNECs expanded at chronic hypoxia, demonstrating epithelial cobblestone morphology and a similar proliferation rate to hNECs expanded at normoxia. Hypoxia-inducible proteins and pathways in stem cells and differentiated cultures were identified. Despite the stem cells’ plasticity and adaptation to chronic hypoxia, the differentiated epithelium was significantly thinner with reduced barrier integrity. Stem cell lineage commitment shifted to a more secretory epithelial phenotype. Motile cilia abundance, length, beat frequency and coordination were significantly negatively modulated. Chronic hypoxia reduces the activity of epithelial sodium and CFTR ion channels. CFTR modulator drug response was diminished. Our findings shed light on the molecular pathophysiology of hypoxia and its implications in CF. Targeting hypoxia can be a strategy to augment mucosal function and may provide a means to enhance the efficacy of CFTR modulators.
Publisher: Wiley
Date: 07-2010
Publisher: Springer Science and Business Media LLC
Date: 09-12-2019
DOI: 10.1038/S41598-019-55028-7
Abstract: Intestinal dysbiosis has been observed in children with cystic fibrosis (CF), yet the functional consequences are poorly understood. We investigated the functional capacity of intestinal microbiota and inflammation in children with CF. Stool s les were collected from 27 children with CF and 27 age and gender matched healthy controls (HC) (aged 0.8–18 years). Microbial communities were investigated by iTag sequencing of 16S rRNA genes and functional profiles predicted using Tax4Fun. Inflammation was measured by faecal calprotectin and M2-pyruvate kinase. Paediatric CF gastrointestinal microbiota demonstrated lower richness and ersity compared to HC. CF s les exhibited a marked taxonomic and inferred functional dysbiosis when compared to HC. In children with CF, we predicted an enrichment of genes involved in short-chain fatty acid (SCFA), antioxidant and nutrient metabolism (relevant for growth and nutrition) in CF. The notion of pro-inflammatory GI microbiota in children with CF is supported by positive correlations between intestinal inflammatory markers and both genera and functional pathways. We also observed an association between intestinal genera and both growth z-scores and FEV1%. These taxonomic and functional changes provide insights into gastrointestinal disease in children with CF and future gastrointestinal therapeutics for CF should explore the aforementioned pathways and microbial changes.
Publisher: Elsevier BV
Date: 2006
Publisher: BMJ
Date: 03-2018
DOI: 10.1136/BMJOPEN-2017-020646
Abstract: Pneumonia is the leading cause of childhood morbidity and mortality globally. Introduction of the conjugate Haemophilus influenzae B and multivalent pneumococcal vaccines in developed countries including Australia has significantly reduced the overall burden of bacterial pneumonia. With the availability of molecular diagnostics, viruses are frequently detected in children with pneumonia either as primary pathogens or predispose to secondary bacterial infection. Many respiratory pathogens that are known to cause pneumonia are also identified in asymptomatic children, so the true contribution of these pathogens to childhood community-acquired pneumonia (CAP) remains unclear. Since the introduction of pneumococcal vaccines, very few comprehensive studies from developed countries have attempted to determine the bacterial and viral aetiology of pneumonia. We aim to determine the contribution of bacteria and viruses to childhood CAP to inform further development of effective diagnosis, treatment and preventive strategies. We are conducting a prospective case–control study (PneumoWA) where cases are children with radiologically confirmed pneumonia admitted to Princess Margaret Hospital for Children (PMH) and controls are healthy children identified from PMH outpatient clinics and from local community immunisation clinics. The case–control ratio is 1:1 with 250 children to be recruited in each arm. Nasopharyngeal swabs are collected from both cases and controls to detect the presence of viruses and bacteria by PCR pathogen load will be assessed by quantitative PCR. The prevalence of pathogens detected in cases and controls will be compared, the OR of detection and population attributable fraction to CAP for each pathogen will be determined relationships between pathogen load and disease status and severity will be explored. This study has been approved by the human research ethics committees of PMH, Perth, Australia (PMH HREC REF 2014117EP). Findings will be disseminated at research conferences and in peer-reviewed journals.
Publisher: Springer Basel
Date: 2015
Publisher: American Thoracic Society
Date: 07-2022
Publisher: Wiley
Date: 15-12-2015
DOI: 10.1111/JPC.12791
Abstract: Primary ciliary dyskinesia (PCD) is a rare (1:15,000) condition resulting in recurrent suppurative respiratory tract infections, progressive lung damage and hearing impairment. As the diagnosis is often delayed for years, the purpose of this study was to review the presenting features of children with PCD attending Australia's initial diagnostic PCD service over a 30-year period. A retrospective review of the symptoms of children diagnosed with PCD at Concord Hospital between 1982 and 2012 was undertaken. One thousand thirty-seven paediatric patients were referred for assessment and underwent nasal ciliary brushing. Eighty-four (8.1%) had PCD based on microscopic analysis of nasal cilia. This included 81 with ciliary ultrastructural abnormalities demonstrated on electron microscopy and 3 with a suggestive phenotype, reduced ciliary beat frequency and a family history of PCD. The median age at diagnosis was 6.4 years (range 0.1 to 18.2 years). Forty-six per cent had situs abnormalities and 31% had a family member with PCD. Recurrent cough (81%), rhinosinusitis (71%), recurrent otitis media (49%) and neonatal respiratory distress (57%) were reported. Bronchiectasis at presentation was documented in 32%. Situs abnormalities and neonatal respiratory distress were present together in 26%. PCD remains under-recognised by health-care workers. The combination of neonatal respiratory distress, chronic suppurative cough and rhinosinusitis was the most common documented symptom cluster at presentation in cases of PCD. A heightened awareness of the clinical features of the disease may help to lower the age at diagnosis, facilitate appropriate treatment and improve long-term outcomes.
Publisher: Wiley
Date: 13-12-2011
DOI: 10.1002/PPUL.21603
Abstract: While it is recognized that beta-blockers can exacerbate asthma symptoms in older children and adults, there are few descriptions of a similar effect in infants. We describe three infants who developed wheeze during treatment with a beta-blocker for infantile hemangiomas and conclude that physicians should inquire about respiratory symptoms in this group of children.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 05-2019
Publisher: Wiley
Date: 08-12-2015
DOI: 10.1002/PPUL.23126
Abstract: This study aimed to assess the effectiveness of the Lung Flute in obtaining a sputum s le from children with cystic fibrosis (CF) that were not productive of sputum with coughing alone. Children attending an outpatient CF clinic who were not able to provide a s le with coughing alone were eligible. Each child used the Lung Flute on two occasions at least one month apart. The primary outcome was expectoration of a sputum s le. Secondary outcomes were sputum microbiology, time taken for the procedure, and ease of use of the device as assessed by the patient using a visual analogue scale (VAS), with 0/10 representing very easy and 10/10 representing very hard. Twenty-five children participated (15 males, mean age 12.7 range 6.5-17.9). Overall, a sputum s le was obtained on 26/50 (52%) uses of the device. In children that presented with a moist cough, a s le was obtained on 17/17 (100%) occasions, compared to 9/33 (27%) occasions when a child presented with a dry cough. A positive culture result for at least one known CF pathogen was found in 24/26 s les. Culture results from obtained s les resulted in management changes in 12 cases. Mean time taken to obtain a s le was 9.8 min (SD 2.2). Mean ease of use on the VAS was 1.5 (SD 1.6). The lung flute appears to be a clinically useful and easy device for sputum induction in children with CF. Further research comparing its effectiveness to other sputum induction methods is warranted.
Publisher: BMJ
Date: 06-2006
Publisher: Informa UK Limited
Date: 27-12-2022
Publisher: WHO Press
Date: 11-12-2013
Publisher: Wiley
Date: 15-05-2009
DOI: 10.1002/PPUL.21067
Publisher: BMJ
Date: 12-2021
DOI: 10.1136/BMJRESP-2021-001127
Abstract: Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening. A multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two ided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two ided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two ided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population. Ethics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences. NCT04638517 Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.JCF.2013.09.001
Abstract: It is unclear whether annual multidisciplinary reviews in cystic fibrosis (CF) patients should be conducted in dedicated annual review (AR) clinics or during continuous assessments throughout the year. Our aim was to assess the effect of introducing an AR clinic. A retrospective written and electronic record review of CF patients was carried out for 2007 (no AR Clinic) and 2010 (established AR Clinic) calendar years. An internet-based satisfaction survey was distributed to families attending the AR clinic. In total, 123 children (mean age 9.5 years, range 1.32-18.8 years) and 141 children (8.3 years, 1.1-18.3 years) were included in 2007 and 2010 respectively. There was a significant increase in multidisciplinary reviews (documented annual review 28% vs 85%, P < 0.001 dietary assessment 46% vs 92%, P < 0.001) and investigations (OGTT 2% vs 74%, P < 0.001 abdominal ultrasound 35% vs 85%, P < 0.001) conducted after the introduction of AR clinic. The majority of the families surveyed (85%) were satisfied or very satisfied with the AR clinic. CF AR clinic significantly improves the number of annual investigations and multidisciplinary reviews performed. Families were satisfied with this new process.
Publisher: BMJ
Date: 03-2009
Publisher: Elsevier
Date: 2018
Publisher: BMJ
Date: 11-07-2018
DOI: 10.1136/ARCHDISCHILD-2016-312495
Abstract: This longitudinal study investigated protective factors for social-emotional well-being in refugee children in Australia. Newly arrived refugee children aged 4–15 years were recruited between 2009 and 2013 and assessments were conducted at two points, at years 2 and 3 postarrival. Social-emotional well-being was assessed using the Strengths and Difficulties Questionnaire (SDQ). Protective factors were assessed by structured interview and the Social Readjustment Rating Scale (SRRS) scores reflect fewer stressful life events in the previous year. Forty-three eligible refugee children were recruited. The SDQ was completed by parents in 90% and protective factor data in 80% at years 2 and 3 of follow-up. Protective factors for normal SDQ scores were: originating from Africa (p=0.01), father present on arrival (p=0.019) and family SRRS scores at year 2 (p=0.045). The median number of protective factors was 4 (range 1–8). Better SDQ scores were associated with ≥4 protective factors (p .006). Furthermore, more protective factors increased the child’s likelihood of a stable or improved SDQ score over time (p .04). Modifiable protective factors likely to promote social-emotional well-being include stability in the child’s school and residence, parental employment, financial and marital stability, proximity to one’s own ethnic community and external community support. Cumulative protective factors, some of which are potentially modifiable, can predict social-emotional well-being in newly arrived refugee children. Children with four or more protective factors are at low risk of poor social-emotional well-being.
Publisher: Wiley
Date: 08-08-2019
DOI: 10.1002/PPUL.24456
Publisher: Elsevier BV
Date: 09-2021
Publisher: Future Medicine Ltd
Date: 06-2008
Abstract: Asthma is one of the most common diseases of childhood and once diagnosed there are many pharmacological methods of managing the symptoms. Yet a subgroup of children with ‘difficult to manage’ asthma still exists that do not appear to respond to standard asthma therapies. While the reason behind this is not entirely known, it is believed that gastroesophageal disease (GERD), which can present with a variety of extraesophageal symptoms, may be partly responsible for the respiratory symptoms observed in such pediatric patients. It is therefore pertinent that the clinician treating a child with ‘difficult’ asthma considers the possibility of GERD-related symptoms. The use of the appropriate GERD monitoring and diagnostic tools can improve the morbidity and quality of life of this group.
Publisher: Cold Spring Harbor Laboratory
Date: 12-12-2021
DOI: 10.1101/2021.12.12.472297
Abstract: Characterisation of I37R – a novel mutation in the lasso motif of ABC-transporter CFTR, a chloride channel – was conducted by theratyping using CFTR potentiators which increase channel gating activity and correctors which repair protein trafficking defects. I37R-CFTR function was characterised using intestinal current measurements (ICM) in rectal biopsies, forskolin-induced swelling (FIS) in intestinal organoids and short circuit current measurements (I sc ) in organoid-derived monolayers from an in idual with I37R/F508del CFTR genotype. We demonstrated that the I37R-CFTR mutation results in a residual function defect amenable to treatment with potentiators and type III, but not to type I, correctors. Molecular dynamics of I37R-CFTR using an extended model of the phosphorylated, ATP-bound human CFTR identified an altered lasso motif conformation which results in an unfavourable strengthening of the interactions between the lasso motif, the regulatory (R) domain and the transmembrane domain two (TMD2). In conclusion, structural and functional characterisation of the I37R- CFTR mutation increases understanding of CFTR channel regulation and provides a potential pathway to access CFTR modulator treatments for in iduals with CF caused by ultra-rare CFTR mutations.
Publisher: BMJ
Date: 2003
Publisher: American Medical Association (AMA)
Date: 20-03-2018
Publisher: Wiley
Date: 30-01-2019
DOI: 10.1111/IRV.12633
Publisher: IntechOpen
Date: 09-06-2021
Publisher: Public Library of Science (PLoS)
Date: 09-01-2019
Publisher: Ubiquity Press, Ltd.
Date: 08-08-2019
DOI: 10.5334/IJIC.S3309
Publisher: AMPCo
Date: 08-2009
Publisher: Elsevier BV
Date: 02-2014
Publisher: BMJ
Date: 12-2004
Publisher: Wiley
Date: 2008
DOI: 10.1002/PPUL.20783
Abstract: Children with orphan lung diseases (defined as a prevalence of <1 in 2000) receive suboptimal care due to a lack of understanding of pathophysiology and management. To develop a low cost, multidisease, web-based registry for children with rare lung diseases. The British Pediatric Orphan Lung Disease (BPOLD) electronic registry was established to provide a web-based method for recording monthly incidence data on nine rare pediatric respiratory diseases (www.bpold.co.uk). An email reporting system was developed which required clinicians to input a username and password to respond following a monthly email reminder. The initial reporting rate was poor despite many registrants. The method for reporting was subsequently streamlined enabling reporting to be done via email by a single mouse-click. A follow-up email, with consent forms as attachments, was automatically sent to positive respondents, with negative responses recorded directly to the database. Non-responders receive a reminder email after 2 weeks. Initially 101 respiratory clinicians registered via the BPOLD site, responding 162 times over 17 months. In the 12 months following redevelopment (total 12 monthly group emails) 143 of 222 BPRS members (64%) have provided 1,001 responses. Forty-eight clinicians (34% of responders) have responded to 10-12 group emails, with the next highest total being those responding to one only. One hundred fifty-eight cases of orphan lung disease have been identified. We have demonstrated the successful establishment of a low cost, web-based registry for children with rare lung diseases. There is an urgent need for European and International collaboration with the establishment of electronic registries for children with rare diseases, if the inequities of health care are to be addressed. A web-based approach, similar to the one we have developed, will enable this.
Publisher: Wiley
Date: 15-05-2014
DOI: 10.1111/RESP.12298
Abstract: The respiratory health effects from tobacco smoking are well described. Cannabis smoke contains a similar profile of carcinogenic chemicals as tobacco smoke but is inhaled more deeply. Although cannabis smoke is known to contain similar harmful and carcinogenic substances to tobacco smoke, relatively little is understood regarding the respiratory health effects from cannabis smoking. There is a need to integrate research on cannabis and respiratory health effects so that gaps in the literature can be identified and the more consistent findings can be consolidated with the purpose of educating smokers and health service providers. This review focuses on several aspects of respiratory health and cannabis use (as well as concurrent cannabis and tobacco use) and provides an update to (i) the pathophysiology (ii) general respiratory health including symptoms of chronic bronchitis and (iii) lung cancer.
Publisher: Ubiquity Press, Ltd.
Date: 26-02-2021
DOI: 10.5334/IJIC.S4093
Publisher: Public Library of Science (PLoS)
Date: 11-02-2020
Publisher: Springer Science and Business Media LLC
Date: 2004
DOI: 10.1007/S00247-003-1059-6
Abstract: Chronic pneumonitis of infancy (CPI) is a very rare entity. We report the chest radiography and high-resolution CT (HRCT) findings in an infant with histopathologically confirmed CPI. The child was admitted for intensive care 18 h after birth and died at 39 days of age. On HRCT there was diffuse ground-glass change, interlobular septal thickening and discrete centrilobular nodules. An accurate diagnosis is crucial for correct management however, several entities with the same HRCT findings are recognized.
Publisher: American Psychological Association (APA)
Date: 11-2019
DOI: 10.1037/SPQ0000311
Abstract: Students with chronic illness generally have higher school needs than their healthy peers. The research to date examining school support for these needs has been limited to qualitative methods. We collected quantitative data to compare the school needs and supports received by 192 students with chronic illness and 208 students without chronic illness using parent-completed surveys. We assessed school experiences and receipt of school support across academic, social-emotional, and medical domains and school attendance. We analyzed the data using logistic regression. Students with chronic illness were 3.8 times more likely to have repeated a grade, 3.6 times more likely to have parent-reported academic challenges, and 4.9 times more likely to have recent illness-related school absenteeism than healthy students. Parents of students with chronic illness were 2.2 times more likely to report their child to have moderate-high emotional distress, and 4.6 times more likely to report that their child had low social confidence compared with parents of healthy students. Students with chronic illness did not receive more school-based tutoring, home-based tutoring, or support from a teacher's aide or school psychologist than healthy students. Students with chronic illness receive insufficient support to address their academic and social-emotional needs or high rates of school absenteeism. Evidence-based educational services must be developed and delivered to meet the needs of students with chronic illness at school and while recovering at home. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JCF.2012.11.002
Abstract: To evaluate safety and efficacy of inhaled mannitol treatment in subgroups of a large global CF population. Data were pooled from two multicentre, double-blind, randomised, controlled, parallel group phase III studies in which 600 patients inhaled either mannitol (400 mg) or control (mannitol 50 mg) twice a day for 26 weeks. Both the mean absolute change in FEV(1) (mL) and relative change in FEV(1) by % predicted from baseline for mannitol (400 mg) versus control were statistically significant (73.42 mL, 3.56%, both p<0.001). Increases in FEV(1) were observed irrespective of rhDNase use. Significant improvements in FEV1 occurred in adults but not children (6-11) or adolescents (aged 12-17). Pulmonary exacerbation incidence was reduced by 29% (p=0.039) in the mannitol (400 mg) group. Sustained six-month improvements in lung function and decreased pulmonary exacerbation incidence indicate that inhaled mannitol is an important additional drug in the treatment of CF.
Publisher: Springer Basel
Date: 2015
Publisher: Elsevier BV
Date: 12-2008
Publisher: Elsevier BV
Date: 08-2015
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.EARLHUMDEV.2013.03.003
Abstract: Immigration is increasingly common worldwide and its impact on neonatal intensive care unit outcomes is uncertain. To determine the outcomes of children of immigrant mothers admitted to NICUs in New South Wales (NSW), Australia, between 2000 and 2006. Record linkage study of routinely collected state-based health databases. Infants of Australian-born (9813, 81.9%) and overseas born mothers (2166, 18.1%). NICU and childhood outcomes to a maximum 5 years of age. Immigrant mothers came from 122 countries, 897 (44%) from high income regions. Australian born mothers were more likely to be teenaged (Odds Ratio, 95% confidence interval: 3.07, 2.21-4.26), use drugs (3.55, 2.49-5.06) and suffer an antepartum hemorrhage (1.29, 1.14-1.48). They were less likely to have gestational diabetes (0.45, 0.38-0.54), fetal distress (0.75, 0.66-0.85) and intrauterine growth restriction (0.80, 0.67-0.93). Their infants were more likely to be admitted to the NICU for prematurity but less likely to have low 5 min Apgar scores (0.81, 0.69-0.93) or a congenital abnormality (0.79, 0.70-0.90). Infants of Middle-Eastern mothers had the lowest hospital survival rate (88.5%). Children of immigrant Asian mothers were least likely to be rehospitalized after NICU discharge (1.66, 1.27-2.17). NICU outcomes are affected by maternal country of birth even within the same ethnic group. Further study regarding the impact of paternal race and immigration status and duration of residency will provide data for the changing cultural environment of global perinatal care.
Publisher: European Respiratory Society
Date: 09-2017
Publisher: Wiley
Date: 2021
DOI: 10.1002/JEV2.12053
Publisher: Cambridge University Press (CUP)
Date: 16-03-2017
DOI: 10.1017/BEC.2017.3
Abstract: Anxiety disorders occur at an increased rate in children with asthma however, there is only a small evidence base to support specific psychological treatments for these children. The current study evaluated the efficacy of a pilot cognitive behavioural treatment (CBT) group intervention for children with asthma and a comorbid anxiety disorder in a case series design. Five children (aged 8–11 years old) with asthma and a comorbid anxiety disorder and their mothers took part in eight 1-hour group treatment sessions. Primary outcomes measures were anxiety diagnosis and asthma-related quality of life. Secondary outcome measures were asthma symptom control and parent quality of life associated with caring for a child with asthma. Three of the participants no longer met diagnostic criteria for an anxiety disorder following treatment and three different participants reported a reliable improvement in asthma-related quality of life. Two participants reported a reliable improvement in asthma symptom control. Three mothers reported an improvement in caregiver quality of life. The findings provide preliminary proof of concept evidence for the efficacy of a CBT intervention for children with asthma and clinical anxiety.
Publisher: Wiley
Date: 10-2021
DOI: 10.1002/HSR2.410
Publisher: Springer Basel
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 10-07-2006
DOI: 10.1007/S00005-006-0029-8
Abstract: Clinical phenotype varies amongst cystic fibrosis (CF) patients with identical CF transmembrane regulator (CFTR) genotype, suggesting genetic modifiers exist. One potential modifier is the Toll-like receptor 4 (TLR4) gene. TLR4 binds lipopolysaccharide (LPS), a constituent of Pseudomonas aeruginosa (PA), activating innate immunity and promoting inflammation. TLR4 polymorphisms are associated with LPS-hyporesponsiveness and may be protective in CF due to decreased inflammation. DNA was extracted from blood of recruited CF subjects, and PCR performed to establish TLR4 D299G genotype. Case-notes were reviewed to obtain clinical data. Subjects possessing the TLR4 299G allele were compared with age, sex, and CFTR genotype-matched wild-type (299DD) subjects and also with all controls. 100 subjects (mean age 8.9 years) were studied, with 11 299DG heterozygotes identified. On case-matched analyses, no statistically significant differences between groups were found for mean +/- SEM rates of change of %predicted FEV(1)/year (0.9 +/- 2.3 (DD) vs. - 3.9 +/- 2.8 (DG), p = 0.22), %predicted FEV(1) (76 +/- 8 vs. 74 +/- 11), p = 0.91), or z scores for height ( - 0.47 +/- 0.26 vs. - 0.24 +/- 0.19, p = 0.48) and weight ( - 0.01 +/- 0.22 vs. - 0.29 +/- 0.27, p = 0.44). Median +/- SE survival age at first PA isolation was also not significantly different (3.5 +/- 2.1 vs. 6.5 +/- 2.4 years, p = 0.29). No statistically significant differences were noted when 299DG heterozygotes were compared with all controls. Potential reasons for absence of modifier effect include the basolateral location of TLR4 receptors on respiratory epithelium, or because inflammatory response to PA in the CF airway is so overwhelming that even a blunted response (as suggested for the 299G allele) results in increased inflammation and lung damage.
Publisher: Elsevier BV
Date: 2022
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1038/MT.2008.38
Abstract: Synthetic vectors for cystic fibrosis (CF) gene therapy are required that efficiently and safely transfect airway epithelial cells, rather than alveolar epithelial cells or macrophages, and that are nonimmunogenic, thus allowing for repeated delivery. We have compared several vector systems against these criteria including GL67, polyethylenimine (PEI) 22 and 25 kd and two new, synthetic vector formulations, comprising a cationic, receptor-targeting peptide K(16)GACSERSMNFCG (E), and the cationic liposomes (L) DHDTMA/DOPE or DOSEP3/DOPE. The lipid and peptide formulations self assemble into receptor-targeted nanocomplexes (RTNs) LED-1 and LED-2, respectively, on mixing with plasmid (D). LED-1 transfected airway epithelium efficiently, while LED-2 and GL67 preferentially transfected alveolar cells. PEI transfected airway epithelial cells with high efficiency, but was more toxic to the mice than the other formulations. On repeat dosing, LED-1 was equally as effective as the single dose, while GL67 was 30% less effective and PEI 22 kd displayed a 90% reduction of efficiency on repeated delivery. LED-1 thus was the only formulation that fulfilled the criteria for a CF gene therapy vector while GL67 and LED-2 may be appropriate for other respiratory diseases. Opportunities for PEI depend on a solution to its toxicity problems. LED-1 formulations were stable to nebulization, the most appropriate delivery method for CF.
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: American Chemical Society (ACS)
Date: 28-03-2023
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/IMJ.13166
Abstract: Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway however, effectiveness data in a population with significant comorbidities are limited. To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting.
Publisher: Wiley
Date: 22-08-2003
DOI: 10.1002/PPUL.10355
Abstract: Lung volume reduction surgery (LVRS) has been used increasingly in adults for treatment of breathlessness caused by severe emphysema.1 It is of particular benefit to patients with a heterogenous anatomic distribution of emphysema, with obvious target areas for resection,2 as it allows an improved chance of reclaiming function from surrounding compressed lung.3 We report on an 8-year-old male with obliterative bronchiolitis in whom LVRS has been used as a measure to significantly improve quality of life and avoid the immediate need for lung transplantation.
Publisher: American Psychological Association (APA)
Date: 11-2019
DOI: 10.1037/SPQ0000315
Abstract: Students with chronic illness may disengage from school, adversely affecting their school outcomes. Positive education targets students' social-emotional well-being (school well-being), which can increase engagement with school. We compared the relationship among positive educational practices, school well-being, and engagement with school as reported by parents of students with and without chronic illness. We used a convergent mixed-methods cross-sectional design. We collected data from 215 parents of school-age children with chronic illness and 212 parents of children without chronic illness. Data assessed positive educational practices, school well-being, and engagement with school, which we analyzed using regression and structural equation models. Forty-nine parents of students with chronic illness completed a telephone interview about their child's school experiences, which we analyzed using content analysis. School well-being was significantly lower among students with chronic illness, compared with students without chronic illness (p = .05). Higher student well-being (p ≤ .001) and higher levels of positive educational practices (p = .002) were associated with higher engagement with school. School well-being mediated the relationship between positive educational practices and engagement with school for students with chronic illness but not students without chronic illness. Parents of children with chronic illness described how positive educational practices and their child's school well-being promoted their child's engagement with school. Parents also reported the negative consequences of low school well-being. Positive educational practices alone may not be sufficient to increase engagement with school in students with low school well-being. Combined preventative and early intervention psychosocial support may best promote engagement with school in students with chronic illness. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Publisher: Elsevier BV
Date: 08-2003
Publisher: Wiley
Date: 11-12-2004
DOI: 10.1002/PPUL.10358
Abstract: High-frequency chest compressions (HFCC) have been suggested as an alternative to conventional chest physiotherapy to aid sputum clearance in patients with cystic fibrosis (CF). We aimed to compare the active cycle of breathing techniques (ACBT) with the Hayek Oscillator Cuirass, performing HFCC on secretion clearance in children with CF during an exacerbation. Ten children (7 males median age, 14 years range, 9-16) received either two supervised sessions using HFCC or two self-treatment ACBT sessions in random order on successive days. Baseline pulmonary function was similar prior to treatments. Sputum weight increased significantly with ACBT compared with HFCC during treatment (5.2 g vs. 1.1 g, P < 0.005, morning 4.1 g vs. 0.7 g, P < 0.01, afternoon). Pulmonary function improved significantly after morning ACBT (forced vital capacity (FVC): 2.67 l to 2.76 l, P < 0.03 forced expiratory volume in 1 sec (FEV1): 1.59 l to 1.62 l, P < 0.03). Following afternoon ACBT, there was a significant increase in FVC (2.64 to 2.79, P < 0.02), but no significant change in FEV1. Pulmonary function did not change at any time following HFCC. Compared with ACBT, HFCC by Hayek Cuirass is not an effective airway clearance treatment modality for children with CF during an infective exacerbation.
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3990938
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.VACCINE.2022.11.006
Abstract: We aimed to assess the direct protective effect of 13 valent pneumococcal conjugate vaccine (13vPCV) against invasive pneumococcal pneumonia (IPP including pneumonia and empyema) in children using a nation-wide case-control study across 11 paediatric tertiary hospitals in Australia. Children < 18 years old admitted with pneumonia were eligible for enrolment. IPP was defined as Streptococcus pneumoniae (SP) cultured or detected by polymerase chain reaction (PCR) from blood or pleural fluid. Causative SP serotype (ST) was determined from blood or pleural fluid SP isolates by molecular methods in PCR positive specimens or else inferred from nasopharyngeal isolates. For each IPP case, 20 population controls matched by age and socio-economic status were s led from the Australian Immunisation Register. Conditional logistic regression was used to estimate the adjusted odds ratio (aOR) of being fully vaccinated with 13vPCV (≥3 doses versus < 3 doses) among IPP cases compared to controls, adjusted for sex and Indigenous status. From February 2015 to September 2018, we enrolled 1,168 children with pneumonia 779 were 13vPCV-eligible and were in idually matched to 15,580 controls. SP was confirmed in 195 IPP cases, 181 of whom had empyema. ST3 and ST19A were identified in 52% (102/195) and 11% (21/195) of IPP cases respectively. The aOR of being fully vaccinated with 13vPCV was 0.8 (95% CI 0.6-1.0) among IPP cases compared to matched controls. We failed to identify a strong direct protective effect of 13vPCV against IPP among Australian children, where disease was largely driven by ST3.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2019
Publisher: Wiley
Date: 20-03-2019
DOI: 10.1113/EP087441
Publisher: Wiley
Date: 21-12-2011
DOI: 10.1111/J.1440-1843.2011.02035.X
Abstract: National surveillance of invasive pneumococcal disease (IPD) includes serotyping Streptococcus pneumoniae (SP) isolates from sterile site cultures. PCR is more sensitive and can identify more SP serotypes (STs) in culture-negative s les. The aim of this study was to determine whether enhanced surveillance of childhood empyema, using PCR, provides additional serotype information compared with conventional surveillance. Pleural fluid (PF) from children with empyema were cultured and tested by PCR to identify SP, targeting the autolysin gene (lytA). Multiplex PCR-based reverse line blot assay was used to identify SP STs. Corresponding IPD surveillance and serotype data were obtained from the National Notifiable Diseases Surveillance System (NNDSS). Eighty-nine children with empyema, aged ≤16 years, were recruited between April 2008 and March 2009, inclusive. SP was isolated from 5/84 (5.9%) PF cultures and by PCR in 43/79 (54.4%) PF s les. Serotypes were unidentifiable in 15 s les. The frequency of six serotypes (or serotype pairs) identified in 28 s les, including one with two serotypes, were: ST1, n = 4/29 (13.8%) ST3, n = 9/29 (31.0%) ST19A, n = 12/29 (41.4%) ST7F/7A, n = 1/29 (3.4%) ST9V/9A, n = 1/29 (3.4%) ST22F/22A, n = 2/29 (6.9%). Over the same period, 361 IPD patients, aged 16 years or less, were notified to NNDSS. Among 331 serotypeable NNDSS isolates (71.5% from blood), the frequencies of ST1 and 3 were significantly lower than in PF s les: ST1, n = 8/331 (2.4% P < 0.05) ST3, n = 13/331 (3.9% P < 0.0001). The use of PCR to identify and serotype SP in culture-negative specimens provides additive information.
Publisher: American Society for Microbiology
Date: 05-2009
DOI: 10.1128/JCM.00014-09
Abstract: Pseudomonas aeruginosa is an important cause of pulmonary infection in cystic fibrosis (CF). Its correct identification ensures effective patient management and infection control strategies. However, little is known about how often CF sputum isolates are falsely identified as P. aeruginosa . We used P. aeruginosa -specific duplex real-time PCR assays to determine if 2,267 P. aeruginosa sputum isolates from 561 CF patients were correctly identified by 17 Australian clinical microbiology laboratories. Misidentified isolates underwent further phenotypic tests, lified rRNA gene restriction analysis, and partial 16S rRNA gene sequence analysis. Participating laboratories were surveyed on how they identified P. aeruginosa from CF sputum. Overall, 2,214 (97.7%) isolates from 531 (94.7%) CF patients were correctly identified as P. aeruginosa . Further testing with the API 20NE kit correctly identified only 34 (59%) of the misidentified isolates. Twelve (40%) patients had previously grown the misidentified species in their sputum. Achromobacter xylosoxidans ( n = 21), Stenotrophomonas maltophilia ( n = 15), and Inquilinus limosus ( n = 4) were the species most commonly misidentified as P. aeruginosa . Overall, there were very low rates of P. aeruginosa misidentification among isolates from a broad cross section of Australian CF patients. Additional improvements are possible by undertaking a culture history review, noting colonial morphology, and performing stringent oxidase, DNase, and colistin susceptibility testing for all presumptive P. aeruginosa isolates. Isolates exhibiting atypical phenotypic features should be evaluated further by additional phenotypic or genotypic identification techniques.
Publisher: Elsevier BV
Date: 03-1999
Publisher: Cold Spring Harbor Laboratory
Date: 28-05-2020
DOI: 10.1101/2020.05.27.119990
Abstract: Glutathione deficiency and chronic bacterial inflammation exacerbates the oxidative stress damage to airways in cystic fibrosis. Improvements to current antioxidant therapeutic strategies are needed. Dietary supplement, γ-glutamylcysteine (GGC), the immediate precursor to glutathione, rapidly boosts cellular glutathione levels following a single dose in healthy in iduals. Efficacy of GGC against Pseudomonas aeruginosa derived lipopolysaccharide (LPS), a prominent factor in mediating both bacterial virulence and host responses, in CF remains unassessed. Primary F508del/F508del mucociliary differentiated bronchial and nasal epithelial cells were created to model LPS-induced oxidative stress and inflammation of CF. The proteomic signature of GGC treated cells was resolved by qLC-MS/MS. Parameters including cell redox state (glutathione, ROS), anti-inflammatory mediators (IL-8, IDO-1) and cellular health (membrane integrity, stress granule formation and cell viability) were assayed. Proteomic analysis identified perturbation of several pathways related to cellular respiration and stress responses upon LPS challenge. Most of these were resolved when cells were treated with GGC. While GGC did not resolve LPS-induced IL-8 and IDO-1 activity, it effectively attenuated LPS-induced ROS and stress granule formation, while significantly increasing intracellular glutathione levels and improving epithelial cell barrier integrity. Moreover, we compared the effect of GGC with thiols NAC and glutathione on cell viability. GGC was the only thiol that increased cell viability protecting cells against LPS induced cell death. Both therapeutic and prophylactic treatments were successful. Together, these findings indicate that GGC has therapeutic potential for treatment and prevention of oxidative stress related damage to airways in Cystic Fibrosis.
Publisher: Springer Science and Business Media LLC
Date: 12-2019
Publisher: Wiley
Date: 26-02-2014
DOI: 10.1111/JPC.12504
Publisher: Wiley
Date: 27-05-2011
DOI: 10.1002/PPUL.21495
Abstract: In cystic fibrosis, gradual pancreatic destruction causes progressive insulin deficiency, culminating in cystic fibrosis related diabetes (CFRD). As a consequence of insulin deficiency, elevated glucose levels can be detected (well before the diagnosis of CFRD), by continuous ambulatory subcutaneous interstitial fluid glucose monitoring or 30-min s led oral glucose tolerance test (OGTT). Current diagnostic criteria for CFRD (based on 0 and 120-min OGTT blood glucose levels) were originally designed to forecast microvascular disease in type 2 diabetes, rather than CF-specific outcomes such as declining weight or lung function. In CF, decline in either weight or lung function predicts early mortality. Both may precede the diagnosis of CFRD by several years. Insulin, a potent anabolic hormone, is recommended treatment for CFRD, but use in earlier stages of insulin deficiency is not established. Conventional dosing (with four or more insulin injections per day) is burdensome and carries substantial risk of hypoglycemia. However, recent uncontrolled trials suggest that once-daily injection of intermediate or long-acting insulin improves weight and lung function, with minimal hypoglycemia risk, in CFRD and also in early insulin deficiency. It is plausible that insulin may be of greater benefit to respiratory function when given prior to the diagnosis of CFRD, after which structural lung disease may be irreversible. It is also plausible that early insulin treatment may prolong the lifespan of the remaining insulin-secreting β-cells. Randomized controlled trials are now needed to determine whether or not current clinical practice should be altered toward the earlier commencement of insulin in CF.
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: 23-09-2010
DOI: 10.1002/PPUL.21379
Publisher: American Thoracic Society
Date: 1999
Abstract: Previous studies have indicated that milrinone, a specific type III phosphodiesterase inhibitor, may be able to induce chloride secretion in cystic fibrosis (CF) tissues. We have now assessed the effect of this agent in vivo on the nasal epithelium of CF mutant mice and also in the nose and lungs of human subjects with CF. Wild-type mice showed a small hyperpolarization of the nasal potential difference (PD) in response to milrinone (100 microM, 1.6 +/- 0.6 mV, n = 8, P < 0.05). In contrast, CF mice carrying either the most common human mutation of the gene for the CF transmembrane regulator (CFTR), DeltaF508 (protein mislocalized), or the G551D mutation (protein normally localized) failed to demonstrate this response. Milrinone perfused alone had no significant effect on the baseline nasal PD of human subjects without CF (14.7 +/- 4.0 mV preperfusion 15.3 +/- 4.6 mV postperfusion), but significantly (P < 0.05) augmented the hyperpolarization induced by a subsequently perfused low-chloride solution (with milrinone, 36.8 +/- 3.0 mV, n = 6 without milrinone, 18.1 +/- 2.2 mV, n = 19). In contrast, in human subjects with CF (n = 6), milrinone alone significantly (P < 0. 05) altered the nasal baseline PD (52.2 +/- 3.3 mV preperfusion 57. 4 +/- 4.2 mV, postperfusion) but not the subsequent responses to the low-chloride solution (with milrinone, 1.1 +/- 2.2 mV, n = 4 without milrinone, 0.6 +/- 0.5 mV, n = 28) or to isoproterenol (100 microM). In a separate study in subjects (n = 6) with the DeltaF508 mutation, nasal coadministration of milrinone with isoproterenol produced no effect in the presence of amiloride and a low-chloride solution (-0.8 +/- 0.5 mV). This was also the case in the nasal epithelium of CF subjects (n = 4) carrying at least one G551D allele (-0.3 +/- 0.8 mV). Similarly, milrinone did not hyperpolarize the PD of either the tracheal (n = 6) or segmental (n = 6) airways of CF subjects (DeltaF508) when applied topically in vivo in the presence of amiloride, isoproterenol, or adenosine triphosphate (all 100 microM) in a low-chloride solution. These data do not support the use of milrinone to induce chloride secretion in CF airways in vivo.
Publisher: Elsevier BV
Date: 06-2008
Publisher: Frontiers Media SA
Date: 11-2022
DOI: 10.3389/FPED.2022.1062766
Abstract: Cystic Fibrosis (CF) results from over 400 different disease-causing mutations in the CF Transmembrane Conductance Regulator ( CFTR ) gene. These CFTR mutations lead to numerous defects in CFTR protein function. A novel class of targeted therapies (CFTR modulators) have been developed that can restore defects in CFTR folding and gating. This study aimed to characterize the functional and structural defects of S945L-CFTR and interrogate the efficacy of modulators with two modes of action: gating potentiator [ivacaftor (IVA)] and folding corrector [tezacaftor (TEZ)]. The response to these modulators in vitro in airway differentiated cell models created from a participant with S945L/G542X-CFTR was correlated with in vivo clinical outcomes of that participant at least 12 months pre and post modulator therapy. In this participants' airway cell models, CFTR-mediated chloride transport was assessed via ion transport electrophysiology. Monotherapy with IVA or TEZ increased CFTR activity, albeit not reaching statistical significance. Combination therapy with TEZ/IVA significantly ( p = 0.02) increased CFTR activity 1.62-fold above baseline. Assessment of CFTR expression and maturation via western blot validated the presence of mature, fully glycosylated CFTR, which increased 4.1-fold in TEZ/IVA-treated cells. The in vitro S945L-CFTR response to modulator correlated with an improvement in in vivo lung function (ppFEV 1 ) from 77.19 in the 12 months pre TEZ/IVA to 80.79 in the 12 months post TEZ/IVA. The slope of decline in ppFEV1 significantly ( p = 0.02) changed in the 24 months post TEZ/IVA, becoming positive. Furthermore, there was a significant improvement in clinical parameters and a fall in sweat chloride from 68 to 28 mmol/L. The mechanism of dysfunction of S945L-CFTR was elucidated by in silico molecular dynamics (MD) simulations. S945L-CFTR caused misfolding of transmembrane helix 8 and disruption of the R domain, a CFTR domain critical to channel gating. This study showed in vitro and in silico that S945L causes both folding and gating defects in CFTR and demonstrated in vitro and in vivo that TEZ/IVA is an efficacious modulator combination to address these defects. As such, we support the utility of patient-derived cell models and MD simulations in predicting and understanding the effect of modulators on CFTR function on an in idualized basis.
Publisher: BMJ
Date: 04-2020
DOI: 10.1136/BMJOPEN-2019-033916
Abstract: Chronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the ‘ E valuating the A limentary and R espiratory T racts in H ealth and disease’ (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions. The EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of in idual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts. Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor. Ethics approval: Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals. NCT04071314
Publisher: American Thoracic Society
Date: 05-2019
DOI: 10.1164/AJRCCM-CONFERENCE.2019.199.1_MEETINGABSTRACTS.A3591
Publisher: Wiley
Date: 18-06-2014
DOI: 10.1111/JPC.12628
Abstract: Primary ciliary dyskinesia (PCD) is a multi-organ disorder associated with chronic oto-sino-pulmonary disease, neonatal respiratory distress, situs abnormalities and reduced fertility. Repeated respiratory tract infections leads to the almost universal development of bronchiectasis. These clinical manifestations are a consequence of poorly functioning motile cilia. However, confirming the diagnosis is quite difficult and is often delayed, so the true incidence of PCD may be significantly higher than current estimates. Nasal nitric oxide has been earmarked as a useful screening tool for identifying patients, but its use is limited in pre-school-aged children. Due to the rarity of PCD, the evidence base for management is somewhat limited, and treatment regimens are extrapolated from other suppurative lung disorders, like cystic fibrosis.
Publisher: Springer Science and Business Media LLC
Date: 31-08-2019
DOI: 10.1007/S10803-019-04195-7
Abstract: Knowledge about the quality of care delivered to children with autism spectrum disorders (ASD) in relation to that recommended by clinical practice guidelines (CPGs) is limited. ASD care quality indicators were developed from CPGs and validated by experts, then used to assess the quality of care delivered by general practitioners (GPs) and pediatricians in Australia. Data were retrospectively collected from the medical records of 228 children (≤ 15 years) with ASD for 2012-2013. Overall quality of care was high, but with considerable variation among indicators, and between GPs and pediatricians-e.g., GPs were less likely to complete the assessment care bundle (61% 95% CI 21-92). Findings highlight potential areas for improvement in the need for standardized criteria for diagnosis.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2015
DOI: 10.1007/S10620-015-3842-2
Abstract: Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively investigated, but the role of the intestinal innate immune system in CF is unknown. Human β-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces and upregulated by inflammation. Its expression in the CF intestine is unknown. To determine whether HBD-2 was present in the feces of patients with CF, and to compare fecal HBD-2 levels between CF and healthy controls (HC). To compare fecal HBD-2 levels in inflamed and noninflamed states, as measured by fecal calprotectin, as a secondary aim. Feces from children with CF and HC were collected for analysis. Thirty-three CF patients and 33 HC were recruited. All CF patients had detectable fecal HBD-2. There was no difference between fecal HBD-2 in CF and HC (median (IQR) 49.1 (19.7-77.2) versus 43.4 (26.5-71.9) ng/g P = 0.7). Fecal calprotectin was significantly higher in the CF cohort than in HC (median (IQR) 61.3 (43.8-143.8) versus 19.5 (19.5-35.1) mg/kg P < 0.0001). There was no difference in fecal HBD-2 levels between CF subjects with fecal calprotectin ≥50 mg/kg and <50 mg/kg (50.5 (19.6-80.2) versus 43.0 (19.0-70.4) P = 0.7). There was no correlation between fecal HBD-2 and calprotectin in CF (r = 0.14 P = 0.4). Fecal HBD-2 levels were not increased in children with CF, in inflamed or noninflamed states. The lack of HBD-2 induction and upregulation under inflammatory conditions may suggest a diminished intestinal innate immune response in CF.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 10-2011
Publisher: Cold Spring Harbor Laboratory
Date: 11-08-2021
DOI: 10.1101/2021.08.11.456003
Abstract: A significant challenge to making targeted CFTR modulator therapies accessible to all in iduals with cystic fibrosis (CF) are many mutations in the CFTR gene that can cause CF, most of which remain uncharacterized. Here, we characterized the structural and functional defects of the rare CFTR mutation R352Q – with potential role contributing to intrapore chloride ion permeation – in patient-derived cell models of the airway and gut. CFTR function in differentiated nasal epithelial cultures and matched intestinal organoids was assessed using ion transport assay and forskolin-induced swelling (FIS) assay respectively. Two CFTR potentiators (VX-770, GLPG1837) and a corrector (VX-809) were tested. Data from R352Q-CFTR were compared to that of participants with mutations with known impact on CFTR function. R352Q-CFTR has residual CFTR function which was restored to functional CFTR activity by CFTR potentiators but not the corrector. Molecular dynamics (MD) simulations of R352Q-CFTR were carried out which indicated the presence of a chloride conductance defect, with little evidence supporting a gating defect. The combination approach of in vitro patient-derived cell models and in silico MD simulations to characterize rare CFTR mutations can improve the specificity and sensitivity of modulator response predictions and aid in their translational use for CF precision medicine.
Publisher: European Respiratory Society (ERS)
Date: 07-2003
Publisher: Elsevier BV
Date: 06-2020
Publisher: Informa UK Limited
Date: 10-2023
DOI: 10.2147/JAA.S446596
Publisher: Cold Spring Harbor Laboratory
Date: 06-04-2021
DOI: 10.1101/2021.04.05.437453
Abstract: Age-dependent differences in the clinical response to SARS-CoV-2 infection is well-documented 1–3 however the underlying molecular mechanisms involved are poorly understood. We infected fully differentiated human nasal epithelium cultures derived from healthy children (1-12 years old), young adults (26-34 years old) and older adults (56-62 years old) with SARS-COV-2 to identify age-related cell-intrinsic differences that may influence viral entry, replication and host defence response. We integrated imaging, transcriptomics, proteomics and biochemical assays revealing age-related changes in transcriptional regulation that impact viral replication, effectiveness of host responses and therapeutic drug targets. Viral load was lowest in infected older adult cultures despite the highest expression of SARS-CoV-2 entry and detection factors. We showed this was likely due to lower expression of hijacked host machinery essential for viral replication. Unlike the nasal epithelium of young adults and children, global host response and induction of the interferon signalling was profoundly impaired in older adults, which preferentially expressed proinflammatory cytokines mirroring the “cytokine storm” seen in severe COVID-19 4,5 . In silico screening of our virus-host-drug network identified drug classes with higher efficacy in older adults. Collectively, our data suggests that cellular alterations that occur during ageing impact the ability for the host nasal epithelium to respond to SARS-CoV-2 infection which could guide future therapeutic strategies.
Publisher: Wiley
Date: 07-2008
DOI: 10.1002/PPUL.20834
Abstract: Invasive aspergillosis (IA) is an aggressive disease with a high mortality rate requiring a high index of clinical suspicion in susceptible patients. We report an atypical presentation of IA, not previously published. A 2-year-old girl with underlying neuroblastoma developed IA, which manifested as fungal pneumonia associated with an intrabronchial polypoid mass.
Publisher: Elsevier BV
Date: 08-2018
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.RESP.2017.02.004
Abstract: Quantitatively measure and validate analysis of neural respiratory drive (NRD) using a commercial polysomnography system in children during sleep. Surface electromyogram of the diaphragm (sEMGdi) recorded from primary snoring children were analysed. A subset was re-analysed to assess intra- and inter-investigator reproducibility. Effects of different band pass filter settings (20-100Hz vs 10-1000Hz) on sEMGdi litude were evaluated. Mean sEMGdi from 45 children aged 4.38 years (median IQR 3.00-7.96) was 5.05μV (SD 2.73). The sEMGdi had a high intra-subject intraclass correlation coefficient (ICC) of 0.88. sEMGdi analysis was reproducible with high ICC between occasions (0.99 95% CI 0.98-0.99) and between investigators (0.98 95% CI 0.97-0.99). There was also a high ICC (0.99, 95% CI 0.96-1.00) between the sEMGdi measured using different band-pass filter settings. Age and BMI were negative predictors of sEMGdi (p<0.0001 and p=0.0004 respectively). NRD in children during sleep as assessed by sEMGdi can be quantified in a reliable and reproducible fashion.
Publisher: Elsevier BV
Date: 06-2007
Publisher: Oxford University Press (OUP)
Date: 09-2021
DOI: 10.1093/CID/CIAB528
Abstract: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with & % of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths & months occurring in the community with in-hospital. We studied 829 RSV-related deaths & year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred & months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months IQR: 0.8−3.3) was lower than in-hospital (2.4 months IQR: 1.5−4.0 P & .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P & 0.0001). We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.
Publisher: Wiley
Date: 27-07-2017
DOI: 10.1002/PPUL.23689
Abstract: Anxiety often presents comorbidly with asthma in youth under 18 however, prevalence rates are unclear. The aim of this review was to provide an up-to-date analysis of the literature investigating the prevalence of anxiety disorders, and comparisons of anxiety disorders and symptomatology in youth with asthma, compared to those without. A systematic search was conducted using the databases PsycINFO, MEDLINE, EMBASE, and CINAHL. The search process produced 15 studies (n = 7443) reporting data on youth with asthma and anxiety disorders, 11 studies (n = 10 332) reporting data on youth with and without asthma and anxiety disorders, and 28 studies (n = 5848) reporting data on youth with and without asthma and anxiety symptomatology. Youth with asthma had an anxiety disorder prevalence rate of 22.7%. Youth with asthma also had a greater number of anxiety disorders, compared to those without asthma (d = 0.37, 95%CI: 0.24-0.50, P < 0.001), and higher levels of anxiety symptomatology than youth without asthma (d = 0.29, 95%CI: 0.19-0.39, P < 0.001). Youth with asthma display a prevalence rate for anxiety disorders that is more than three times higher than the prevalence in healthy youth. For the specific anxiety disorders investigated, elevated prevalence rates for youth with asthma were also found. Future research needs to focus on the factors that mediate or predict the development and maintenance of anxiety in youth with asthma and the development of clinically efficacious treatments.
Publisher: BMJ
Date: 11-04-2018
DOI: 10.1136/ARCHDISCHILD-2017-314631
Abstract: To evaluate research priority setting approaches in childhood chronic diseases and to describe the priorities of stakeholders including patients, caregivers/families and health professionals. We conducted a systematic review of MEDLINE, Embase, PsycINFO and CINAHL from inception to 16 October 2016. Studies that elicited stakeholder priorities for paediatric chronic disease research were eligible for inclusion. Data on the prioritisation process were extracted using an appraisal checklist. Generated priorities were collated into common topic areas. We identified 83 studies (n=15 722). Twenty (24%) studies involved parents/caregivers and four (5%) children. The top three health areas were cancer (11%), neurology (8%) and endocrine/metabolism (8%). Priority topic areas were treatment (78%), disease trajectory (48%), quality of life sychosocial impact (48%), disease onset revention (43%), knowledge/self-management (33%), prevalence (30%), diagnostic methods (28%), access to healthcare (25%) and transition to adulthood (12%). The methods included workshops, Delphi techniques, surveys and focus groups/interviews. Specific methods for collecting and prioritising research topics were described in only 60% of studies. Most reviewed studies were conducted in high-income nations. Research priority setting activities in paediatric chronic disease cover many discipline areas and have elicited a broad range of topics. However, child/caregiver involvement is uncommon, and the methods often lack clarity. A systematic and explicit process that involves patients and families in partnership may help to inform a more patient and family-relevant research agenda in paediatric chronic disease.
Publisher: American Public Health Association
Date: 07-2021
Publisher: Wiley
Date: 10-04-2015
DOI: 10.1111/JGH.12842
Abstract: Adult patients with cystic fibrosis (CF) have an increased risk of gastrointestinal malignancies. We hypothesized that increased intestinal cell turnover beginning in childhood may explain the increased risk of malignancy in early adulthood. Therefore, we aimed to measure fecal M2-pyruvate kinase (M2-PK), a biomarker of intestinal cell turnover, in children with CF. To assess whether the increased cell turnover is secondary to intestinal inflammation, the secondary aims were to measure fecal calprotectin and evaluate its association with fecal M2-PK. Fecal s les, for M2-PK and calprotectin measurements, were prospectively collected from children with CF and healthy controls (HC). Thirty-three children with CF (mean [standard deviation] 7.3 [3.8] years old 29 pancreatic insufficient [PI]) were enrolled and compared with 33 age-matched HC. Fecal M2-PK in CF patients (median [interquartile range, IQR]: 4.7 [1.5-9.7]) was greater than HC (1.0 [1.0-1.0] U/mL P < 0.0001), and higher in PI (median [IQR]: 5.1 [1.8-13.7]) than pancreatic sufficient patients (1.0 [1.0-1.0] U/mL P = 0.002). Fecal calprotectin was significantly elevated in CF than HC (median [IQR] 61.3 [43.8-143.8] vs 19.5 [19.5-35.1] mg/kg P < 0.0001). However, there was no correlation between fecal M2-PK and fecal calprotectin levels among subjects with CF (r = 0.29 P = 0.1). Increased intestinal cell turnover is present in children with PI CF. The lack of relationship between fecal M2-PK and calprotectin suggests that contributing factor(s) other than inflammation may be present.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.JCF.2015.09.001
Abstract: Early detection of bacterial pathogens in the lower airway is an important part of managing CF. This study aimed to assess the diagnostic accuracy of oropharyngeal suction (OPS) s les in obtaining airway bacterial cultures in young children with cystic fibrosis (CF), and the level of child distress caused by obtaining OPS s les. Young children with CF undergoing broncho-alveolar lavage (BAL) as part of concurrent research or routine annual surveillance were studied. OPS was performed by stimulating a cough and suctioning the back of the oropharynx in the awake child to replicate clinical practice. BAL of the right upper, middle and lingula lobes was then performed. S les were sent for standard bacterial culture. The child's distress during OPS was rated using the Groningen Distress Scale (1=calm, 2=timid/nervous, 3=serious distress but still under control, 4=serious distress with loss of control, 5=panic). There were 65 paired s les obtained from 39 children (21 boys, mean age on day of first s ling was 34.1months, SD 19.1months). For Pseudomonas aeruginosa, specificity, sensitivity, NPV and PPV with 95% CI were 98% (87-99), 75% (20-96), 98% (91-98) and 60% (15-93%) respectively. In all age groups combined, median level of distress was 3 (IQR 2-4), with distress highest in 2 and 3year olds, with a median of 4 (IQR 3-4). OPS has diagnostic utility in determining the absence of organisms in the lower airway, with specificity for P.aeruginosa detection of 98%. However, a positive OPS result is not necessarily a good indicator of lower airway infection. Distress levels were high during OPS, mostly in 2 and 3year olds.
Publisher: European Respiratory Society
Date: 09-2017
Publisher: Wiley
Date: 2010
DOI: 10.1111/J.1440-1754.2009.01608.X
Abstract: Australia requires a national plan, similar to plans developed internationally, to address the impacts of rare diseases on in iduals, the community and health services. Rare diseases often present in childhood, many are chronic, some life threatening and others associated with significant disability. However, diagnosis is often delayed, because of lack of knowledge and experience of health professionals and uncertainty about where to refer. Specialised health services are frequently lacking and specific therapies are often not available, partly because of lack of research funding directed towards rare diseases. A national plan would facilitate a coordinated response to service development, carer support, and health professional and community education, and would promote research and advocacy for affected children and their families.
Publisher: Wiley
Date: 16-07-2010
DOI: 10.1002/PPUL.21261
Abstract: A major problem for patients with cystic fibrosis (CF) is the maintenance of adequate nutrition to maintain normal growth. The hypotheses that poor nutrition could be due to smell and/or taste dysfunction has been pursued in several studies with contradictory results. None, however, investigated whether inadequate nutrition is due to CF patients having different liking for foods compared to healthy children and whether liking can be linked to specific changes in smell or taste function. Here, the relationships between food liking, BMI, and smell and taste function in 42 CF and 42 healthy 5- to 18-year olds is pursued. A three-choice 16-item odor identification test and a gustatory identification test involving five concentrations of sweet, sour, bitter, and salty tastes, were used to assess chemosensory function. Food liking was assessed using a 94-item questionnaire. Patients identified significantly fewer odors than controls (89.8% vs. 95.7% correct P < 0.001). However, only a few patients were affected and their loss of olfactory function was not substantial and unlikely to affect their liking for foods. Taste identification was similar for the two groups (patients 92.6% vs. controls 94.2% correct). There was no correlation between age and odor identification ability, but taste performance improved with age (r = 0.39, P < 0.05), suggesting cognition was the cause. Patients liked several types of foods and high-fat foods more than the controls. Both groups had a similar liking for low-fat foods and both liked high-fat foods more than low-fat foods. No significant relationships existed between FEV(1) and smell or taste function or liking for foods, the BMI of the groups were similar and there was no relationship between BMI and smell or taste function. The results indicate that the abnormal eating behavior reported for many CF patients is not due to changes in chemosensory function which remains normal in most CF patients at least to 18 years of age.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 06-2015
Publisher: European Respiratory Society (ERS)
Date: 08-03-1970
DOI: 10.1183/09031936.00187510
Abstract: This international phase III study of inhaled dry powder mannitol was a randomised, double-blind, 26-week study, followed by a further 26-week, open-label (OL) extension. 324 cystic fibrosis (CF) patients were randomised, in a 3:2 ratio, to mannitol (400 mg b.i.d.) and control groups. The primary efficacy end-point was to determine the change in forced expiratory volume in 1 s (FEV₁) over the double-blind phase. Secondary end-points included changes in forced vital capacity and pulmonary exacerbations. A significant improvement in FEV₁ was seen over 26 weeks (p<0.001) and was apparent by 6 weeks, irrespective of concomitant recombinant human deoxyribonuclease (rhDNase) use. At 26 weeks, there was a significant improvement in FEV₁ of 92.9 mL for subjects receiving mannitol compared with controls (change from baseline 118.9 mL (6.5%) versus 26.0 mL (2.4%) p<0.001). Improvements in FEV₁ were maintained up to 52 weeks in the OL part of the study. There was a 35.4% reduction in the incidence of having an exacerbation on mannitol (p=0.045). The incidence of adverse events (AEs) was similar in both groups, although treatment-related AEs were higher in the mannitol compared with the control group. The most common mannitol-related AEs were cough, haemoptysis and pharyngolaryngeal pain. Mannitol showed sustained, clinically meaningful benefit in airway function in CF, irrespective of concomitant rhDNase use. Mannitol appears to have an acceptable safety profile for patients with CF.
Publisher: BMJ
Date: 06-2016
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JCF.2012.08.007
Abstract: To determine the safety and efficacy of stoss therapy on vitamin D levels over a 12 month period in children with cystic fibrosis and vitamin D deficiency (<75 nmol/L). Retrospective chart review of 142 paediatric CF patients from 2007 till 2011. Thirty eight children received stoss therapy and 37 children with vitamin D deficiency were not treated and served as a control group. The stoss treated group had a significant and sustained increase in 25-hydroxyvitamin D levels measured at 1, 3, 6 and 12 months post treatment compared to controls (94.82 ± 41.0 nmol/L, p=0.001 81.54 ± 24.6 nmol/L, p=0.001 92.18 ± 36.5 nmol/L, p=0.008 and 64.6 ± 20.0 nmol/L, p=0.006 respectively). At 12 months post intervention, the mean difference in vitamin D levels from baseline between the stoss treated group and controls was significant at 15 nmol/L compared to 5 nmol/L (p=0.038). Stoss therapy effectively achieves and maintains levels of 25-hydroxyvitamin D greater than 75 nmol/L over 12 months.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2021
Publisher: Wiley
Date: 12-02-2018
Publisher: Elsevier BV
Date: 2014
Publisher: Annual Reviews
Date: 07-2018
Publisher: SAGE Publications
Date: 2023
Publisher: AMPCo
Date: 09-2008
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 08-09-2016
DOI: 10.1002/JMV.24371
Abstract: Much of what is known about the seasonality of human rhinovirus (hRV) infections has been learned from the study of acute asthma exacerbations presenting to emergency care, including those among children at the start of the school term. Much less is known about the patterns of hRVs in the community. In this study, viruses and day-to-day symptoms of asthma and colds were monitored twice weekly in 67 children with asthma aged 5-12 years, over a 15 month period in Sydney, Australia. Overall hRV was detected in 314/1232 (25.5%) of nasal wash s les and 142/1231 (11.5%) of exhaled breath s les of these, 231 and 24 respectively were genotyped. HRVs were detected with similar prevalence rate throughout the year, including no peak in hRV prevalence following return to school. No peaks were seen in asthma and cold symptoms using twice-weekly diary records. However, over the same period in the community, there were peaks in asthma emergency visits both at a large local hospital and in state-wide hospitalizations, following both return to school (February) and in late autumn (May) in children of the same age. This study suggests that hRV infections are common throughout the year among children, and differences in virus prevalence alone may not account for peaks in asthma symptoms.
Publisher: Wiley
Date: 07-2009
DOI: 10.1002/PPUL.21036
Abstract: Primary immunodeficiency is a common cause of bronchiectasis in children. The term bronchiectasis suggests an irreversible process however, disease progression following treatment is controversial. The aim of this study was to evaluate the progression of bronchiectasis in children with primary immunodeficiency after institution of treatment. A retrospective review of case notes of children with primary immunodeficiency was undertaken to identify patients with confirmed bronchiectasis. Children who had two high-resolution computed tomography scans of the chest (HRCT chest) with an interval of at least 2 years were identified. The HRCT-chest scans at diagnosis and follow up were scored using a Bhalla score. Spirometry results (FEV1, FVC, and FEV1:FVC ratios) were related to HRCT-chest scores, where available. Statistical analysis was by Wilcoxon signed rank test and Spearman's rank order correlation. Eighteen subjects were studied. The diagnosis of primary immunodeficiency was established at median (range) age 3.4 (1-13) years, and bronchiectasis at 9.3 (3.1-13.8) years. There was no significant difference between baseline and follow-up median (range) HRCT-chest scores (6 [1-13] and 7.5 [0-15], P = 0.21) respectively. The follow-up FEV1 and FVC percent predicted median (range) were significantly higher than baseline (86% [49-124%] vs. 75% [36-93%], P < 0.005, and 86% [47-112%] vs. 78% [31-96%], P < 0.05), respectively there was no significant difference between baseline and follow-up FEV(1):FVC ratios. There was no significant correlation between HRCT-chest score changes and FEV1 or FVC changes. Bronchiectasis secondary to primary immunodeficiency in childhood is not always a progressive condition, suggesting a potential to slow or prevent disease progression with appropriate treatment.
Publisher: Informa UK Limited
Date: 05-02-2020
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.JCF.2007.11.006
Abstract: Young adults with cystic fibrosis (CF) frequently develop bone disease. One suggested aetiological factor is suboptimal vitamin K status with impaired carboxylation of osteocalcin and abnormal bone formation. We measured bone mineralization and turnover in thirty-two 8-12 year old CF patients (14 boys) using Dual Energy X-ray absorptiometry (whole body (WB) and lumbar spine (LS)), 25-OH Vitamin D, PTH and markers of bone formation (plasma osteocalcin, N-terminal pro-peptide of type 1 collagen (P1NP)), plus an indirect measure of vitamin K status, undercarboxylated osteocalcin (uc-OC). LS bone mineral density (BMD) standard deviation (SD) scores were < -1.0 in 20% of subjects. Size-adjusted LS and WB bone mass was normal. Compared to reference data, % uc-OC was high and P1NP low. LS bone mass was predicted by % uc-OC but not other markers (0.4% decrease in size-adjusted LSBMC (p=0.05) 0.04 SD decrease in LSBMAD (p=0.04) per 1% increase in uc-OC). Markers suggestive of sub-optimal vitamin K status and low bone formation were present despite normal size-adjusted bone mass. The association between LSBMC and % uc-OC is consistent with the hypothesis that sub-optimal vitamin K status is a risk factor for CF bone disease. This should ideally be investigated in an intervention trial.
Publisher: Elsevier BV
Date: 03-2015
Publisher: European Respiratory Society (ERS)
Date: 16-02-2021
Publisher: Elsevier
Date: 2021
Publisher: Springer Basel
Date: 2016
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/948367
Abstract: There is evidence of intestinal inflammation in patients with CF. Intestinal inflammation may negatively impact the nutritional status of patient with CF, which adversely affects pulmonary function and survival. This paper provides an up-to-date review of intestinal inflammation in CF and an evaluation of utility of two specific faecal inflammatory markers (S100A12 and calprotectin).
Publisher: BMJ
Date: 1998
DOI: 10.1136/JMG.35.1.72
Publisher: Wiley
Date: 08-2016
DOI: 10.1111/PED.13063
Abstract: A number of studies utilizing metabolomics have focused on the pathophysiology of cystic fibrosis (CF) lung disease. Here, we performed fecal metabolomics on pancreatic insufficient (PI) and sufficient (PS) children with CF and compared them with healthy controls (HC). Fecal metabolomics can differentiate between PS-CF and PI-CF. We identified a potential biomarker of disease severity or cystic fibrosis transmembrane conductance regulator function (m/z, 463.247 retention time, 0.570717 min) that discriminates between HC versus PS-CF versus PI-CF. We also identified lipoyl-GMP as a potential novel inflammatory biomarker, and elevation in fecal glycerol 1,2-didodecanoate 3-tetradecanoate may provide clues to the pathogenesis of intestinal inflammation. For the first time, we demonstrate the potential applications of fecal metabolomics in CF.
Publisher: SAGE Publications
Date: 11-2020
Abstract: A common method of learning about adverse events (AEs) is by reviewing medical records using the global trigger tool (GTT). However, these studies generally report rates of harm. The aim of this study is to characterise paediatric AEs detected by the GTT using descriptive and qualitative approaches. Medical records of children aged 0–15 were reviewed for presence of harm using the GTT. Records from 2012–2013 were s led from hospital inpatients, emergency departments, general practice and specialist paediatric practices in three Australian states. Nurses undertook a review of each record and if an AE was suspected a doctor performed a verification review of a summary created by the nurse. A qualitative content analysis was undertaken on the summary of verified AEs. A total of 232 AEs were detected from 6,689 records reviewed. Over four-fifths of the AEs (193/232, 83%) resulted in minor harm to the patient. Nearly half (112/232, 48%) related to medication/intravenous (IV) fluids. Of these, 83% (93/112) were adverse drug reactions. Problems with medical devices/equipment were the next most frequent with nearly two-thirds (32/51, 63%) of these related to intravenous devices. Problems associated with clinical processes rocedures comprise one in six AEs (38/232, 16%), of which diagnostic problems (12/38, 32%) and procedural complications (11/38, 29%) were the most frequent. Adverse drug reactions and issues with IVs are frequently identified AEs reflecting their common use in paediatrics. The qualitative approach taken in this study allowed AE types to be characterised, which is a prerequisite for developing and prioritising improvements in practice.
Publisher: MDPI AG
Date: 05-08-2020
Abstract: The Australian Asthma Handbook does not recommend use of fixed dose combination (FDC) controller medicines for asthma in children aged ≤5 years. FDCs are only recommended in children and adolescents (aged 6–18 years) not responding to initial inhaled corticosteroid (ICS) therapy. Using Pharmaceutical Benefits Scheme dispensing claims from 2013–2018, we examined the annual incident FDC dispensing and the incident FDC dispensing without prior ICS up to 365 days. We also determined cost of FDCs to government and patients. During 2013–2018, there were 35,635 FDC initiations and 31,368 (88%) did not have a preceding ICS dispensing. The annual incidence of FDC dispensing declined from 14.7 to 7.2/1000 children. Incidence of FDC dispensing/1000 children without a preceding ICS declined from 2.1 to 0.5 in children aged 1–2 years, 7.2 to 1.7 in 3–5 years, 14.8 to 5.1 in 6–11 years, and 18.6 to 11.9 in ≥12years. The cost of FDCs was 7.8 million Australian dollars (AUD) of which 4.4 million AUD was to government and 3.3 million AUD was to patient. Despite inappropriate dispensing of FDCs in children aged ≤5 years, incidence of FDC dispensing and more importantly incidence without a preceding ICS is declining in Australia.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2020
DOI: 10.1186/S12887-020-02052-6
Abstract: Infections caused by antibiotic resistant pathogens are increasing, with antibiotic overuse a key contributing factor. The CareTrack Kids (CTK) team assessed the care of children in Australia aged 0–15 years in 2012 and 2013 to determine the proportion of care in line with clinical practice guidelines (CPGs) for 17 common conditions. This study analyses indicators relating to paediatric antibiotic overuse to identify those which should be prioritised by antimicrobial stewardship and clinical improvement programs. A systematic search was undertaken for national and international CPGs relevant to 17 target conditions for Australian paediatric care in 2012–2013. Recommendations were screened and ratified by reviewers. The s ling frame comprised three states containing 60% of the Australian paediatric population (South Australia, New South Wales and Queensland). Multi-stage cluster s ling was used to select general practices, specialist paediatric practices, emergency departments and hospital inpatient services, and medical records within these. Medical records were reviewed by experienced paediatric nurses, trained to assess eligibility for indicator assessment and compliance with indicators. Adherence rates were estimated. Ten antibiotic overuse indicators were identified three for tonsillitis and one each for seven other conditions. A total of 2621 children were assessed. Estimated adherence for indicators ranged from 13.8 to 99.5% while the overall estimate of compliance was 61.9% (95% CI: 47.8–74.7). Conditions with high levels of appropriate avoidance of antibiotics were gastroenteritis and atopic eczema without signs of infection, bronchiolitis and croup. Indicators with less than 50% adherence were asthma exacerbation in children aged 2 years (47.1% 95% CI: 33.4–61.1), sore throat with no other signs of tonsillitis (40.9% 95% CI: 16.9, 68.6), acute otitis media in children aged 12 months who were mildly unwell (13.8% 95% CI: 5.1, 28.0), and sore throat and associated cough in children aged 4 years (14.3% 95% CI: 9.9, 19.7). The results of this study identify four candidate indicators (two for tonsillitis, one for otitis media and one for asthma) for monitoring by antibiotic stewardship and clinical improvement programs in ambulatory and hospital paediatric care, and intervention if needed.
Publisher: Springer Science and Business Media LLC
Date: 08-2012
DOI: 10.2165/11597360-000000000-00000
Abstract: Asthma is a prevalent health condition in children, with economic implications for the in idual and their family, as well as for societies with nationalized healthcare. Pharmaceutical cost is the main driver of healthcare expenditure in asthma. Existent explicit guidelines are meant to guide asthma management across all age groups, but they are failing. Pharmacologic management of asthma consists of a stepwise treatment approach to achieve symptom control. Various studies suggest a significant number of medical practitioners are prescribing inhaled corticosteroids (ICS) and ICS/long-acting beta agonist (LABA) combination inhalers inappropriately, including prescribing high doses of ICS without specialist consultation. ICS/LABA combination inhalers should only be used in persistent asthmatics, which account for approximately 5% of all children with asthma. Despite this, there is an increase in prescribing rates of ICS/LABA combination inhalers in the context of a decrease in the prevalence of asthma. Furthermore, there is inappropriate prescribing of ICS/LABA combination inhalers in children under 5 years of age, and initiation of relatively more expensive ICS/LABA combination inhalers in patients who have not previously been prescribed ICS. There is evidence to suggest that cost is a significant barrier to asthma management, especially for the more expensive ICS/LABA combination inhalers. Hence, prescribing cost-effective asthma medications appropriately is one of the most important strategies in reducing the morbidity and mortality associated with asthma. It is incumbent on every medical practitioner to not prescribe expensive medications if not indicated, both for the sake of the patient and for society.
Publisher: BMJ
Date: 04-2010
Publisher: BMJ
Date: 04-2021
DOI: 10.1136/BMJGH-2020-004010
Abstract: Despite acute respiratory infections (ARIs) being the single largest reason for antibiotic use in under-5 children in Bangladesh, the prevalence of antibiotic use in the community for an ARI episode and factors associated with antibiotic use in this age group are unknown. We analysed nationally representative, population-based, household survey data from the Bangladesh Demographic and Health Survey 2014 to determine the prevalence of antibiotic use in the community for ARI in under-5 children. Using a causal graph and multivariable logistical regression, we then identified and determined the sociodemographic and antibiotic source factors significantly associated with the use of antibiotics for an episode of ARI. We analysed data for 2 144 children aged years with symptoms of ARI from 17 300 households. In our s le, 829 children (39%) received antibiotics for their ARI episode (95% CI 35.4% to 42.0%). Under-5 children from rural households were 60% (adjusted OR (aOR): 1.6 95% CI 1.2 to 2.1) more likely to receive antibiotics compared with those from urban households, largely driven by prescriptions from unqualified or traditional practitioners. Private health facilities were 50% (aOR: 0.5 95% CI 0.3 to 0.7) less likely to be sources of antibiotics compared with public health facilities and non-governmental organisations. Age of children, sex of children or household wealth had no impact on use of antibiotics. In this first nationally representative analysis of antibiotic use in under-5 children in Bangladesh, we found almost 40% of children received antibiotics for an ARI episode. The significant prevalence of antibiotic exposure in under-5 children supports the need for coordinated policy interventions and implementation of clinical practice guidelines at point of care to minimise the adverse effects attributed to antibiotic overuse.
No related grants have been discovered for Adam Jaffe.