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AIM: To describe the effect of resuscitation with bubble CPAP (bCPAP) versus T-piece device at birth on early clinical parameters and hospital outcomes in infants born <32 weeks gestation. METHODS: This is a single-centre pre- and post-implementation study comparing outcomes in two epochs. In epoch 1 (1 July 2013-31 December 2014), infants were managed with non-humidified gas using Neopuff® T-piece devices to support breathing after birth. In epoch 2 (1 March 2020-31 December 2021), routine application of bCPAP with humidified gas was introduced at birth. RESULTS: Three hundred fifty-seven patients were included (176 epoch 1, 181 epoch 2). The mean gestational age was 28 ± 2 weeks. The demographics of the two epochs were comparable. There were significant improvements in outcomes of infants in epoch 2 with less infants intubated at delivery (16% vs. 4%, P ≤ 0.001), improved 5 min Apgar (7 vs. 8, P ≤ 0.001), reduced need for ventilation (21% vs. 8.8%, P ≤ 0.001), duration of ventilation in the first 72 h (9.6 vs. 4.6 h) and mortality (10.8% vs. 1.7%, P ≤ 0.001). There was, increased incidence of chronic lung disease (30% vs. 55%, P = 0.02) but no increase in infants discharged on oxygen (3.8% vs. 5%, P = 0.25). Similar findings were observed in a subgroup of infants born <25 weeks' gestation with no increase in the incidence of CLD. CONCLUSION: Introducing application of bCPAP from the first breaths in infants <32 weeks' gestation was associated with better short-term outcomes and mortality, albeit with increased incidence of CLD. The subgroup of infants born <25 weeks' gestation showed similar change in outcomes, with no increase in CLD.
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BACKGROUND: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. METHODS: 50 CF subjects (mean±SD 11.2 ± 3.5y, range 5-18y) with early lung disease (FEV1≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT). RESULTS: CT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond 82 %, MBWTG RV 78 %, LCI 74 %, MBWTG IC 68 % and Sacin 51 %. CPET VO2peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scond correlated with bronchiectasis (r = 0.55-0.64, p < 0.001) and AT (r = 0.73-0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %. CONCLUSIONS: Significant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.
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Obstructive sleep apnea (OSA) due to a hypertrophy of the adenoids and/or the tonsils in otherwise healthy children is associated with neurocognitive dysfunction and behavioural disorders with various degrees of hyperactivity, aggressiveness, sometimes evolving to a label of attention-deficit hyperactivity disorder. Children with anatomical and/or functional abnormalities of the upper airways represent a very specific population which is at high risk of OSA (also called complex OSA or OSA type III). Surprisingly, the neurocognitive consequences of OSA have been poorly studied in these children, despite the fact that OSA is more common and more severe than in their healthy counterparts. This may be explained by that fact that screening for OSA and sleep-disordered breathing is not systematically performed, the performance of sleep studies and neurocognitive tests may be challenging, and the respective role of the underlining disease, OSA, but also poor sleep quality, is complex. However, the few studies that have been performed in these children, and mainly children with Down syndrome, tend to show that OSA, but even more disruption of sleep architecture and poor sleep quality, aggravate the neurocognitive impairment and abnormal behaviour in these patients, underlining the need for a systematic and early in life assessment of sleep and neurocognitive function and behaviour in children with OSA type III.
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OBJECTIVE: Awareness of the need for early identification and treatment of sleep disordered breathing (SDB) in neonates is increasing but is challenging. Unrecognised SDB can have negative neurodevelopmental consequences. Our study aims to describe the clinical profile, risk factors, diagnostic modalities and interventions that can be used to manage neonates with SDB to facilitate early recognition and improved management. METHODS: A single-centre retrospective study of neonates referred for assessment of suspected SDB to a tertiary newborn intensive care unit in New South Wales Australia over a 2-year period. Electronic records were reviewed. Outcome measures included demographic data, clinical characteristics, comorbidities, reason for referral, polysomnography (PSG) data, interventions targeted to treat SDB and hospital outcome. Descriptive analysis was performed and reported. RESULTS: Eighty neonates were included. Increased work of breathing, or apnoea with oxygen desaturation being the most common reasons (46% and 31%, respectively) for referral. Most neonates had significant comorbidities requiring involvement of multiple specialists (mean 3.3) in management. The majority had moderate to severe SDB based on PSG parameters of very high mean apnoea-hypopnoea index (62.5/hour) with a mean obstructive apnoea index (38.7/hour). Ten per cent of patients required airway surgery. The majority of neonates (70%) were discharged home on non-invasive ventilation. CONCLUSION: SDB is a serious problem in high-risk neonates and it is associated with significant multisystem comorbidities necessitating a multidisciplinary team approach to optimise management. This study shows that PSG is useful in neonates to diagnose and guide management of SDB.
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Comorbidade , Polissonografia , Síndromes da Apneia do Sono , Humanos , Estudos Retrospectivos , Recém-Nascido , Síndromes da Apneia do Sono/terapia , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/diagnóstico , Masculino , Feminino , New South Wales/epidemiologia , Fatores de Risco , Unidades de Terapia Intensiva NeonatalRESUMO
The impact of evolving treatment regimens, airway clearance strategies, and antibiotic combinations on the incidence and prevalence of respiratory infection in cystic fibrosis (CF) in children and adolescents remains unclear. The incidence, prevalence, and prescription trends from 2002 to 2019 with 18,339 airway samples were analysed. Staphylococcus aureus [- 3.86% (95% CI - 5.28-2.43)] showed the largest annual decline in incidence, followed by Haemophilus influenzae [- 3.46% (95% CI - 4.95-1.96)] and Pseudomonas aeruginosa [- 2.80%95% CI (- 4.26-1.34)]. Non-tuberculous mycobacteria and Burkholderia cepacia showed a non-significant increase in incidence. A similar pattern of change in prevalence was observed. No change in trend was observed in infants < 2 years of age. The mean age of the first isolation of S. aureus (p < 0.001), P. aeruginosa (p < 0.001), H. influenza (p < 0.001), Serratia marcescens (p = 0.006) and Aspergillus fumigatus (p = 0.02) have increased. Nebulised amikacin (+ 3.09 ± 2.24 prescription/year, p = 0.003) and colistin (+ 1.95 ± 0.3 prescriptions/year, p = 0.032) were increasingly prescribed, while tobramycin (- 8.46 ± 4.7 prescriptions/year, p < 0.001) showed a decrease in prescription. Dornase alfa and hypertonic saline nebulisation prescription increased by 16.74 ± 4.1 prescriptions/year and 24 ± 4.6 prescriptions/year (p < 0.001). There is a shift in CF among respiratory pathogens and prescriptions which reflects the evolution of cystic fibrosis treatment strategies over time.
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Fibrose Cística , Pneumonia , Infecções por Pseudomonas , Criança , Lactente , Humanos , Adolescente , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/microbiologia , Staphylococcus aureus , Sistema Respiratório/microbiologia , Antibacterianos/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Pneumonia/tratamento farmacológico , Pseudomonas aeruginosaRESUMO
There is an increasing demand for the assessment of sleep-disordered breathing in children of all ages to prevent the deleterious neurocognitive and behaviour consequences of the under-diagnosis and under-treatment of obstructive sleep apnoea [OSA]. OSA can be considered in three broad categories based on predominating contributory features: OSA type 1 [enlarged tonsils and adenoids], type II [Obesity] and type III [craniofacial abnormalities, syndromal, storage diseases and neuromuscular conditions]. The reality is that sleep questionnaires or calculations of body mass index in isolation are poorly predictive of OSA in individuals. Globally, the access to testing in tertiary referral centres is comprehensively overwhelmed by the demand and financial cost. This has prompted the need for better awareness and focussed history taking, matched with simpler tools with acceptable accuracy used in the setting of likely OSA. Consequently, we present key indications for polysomnography and present scalable, existing alternatives for assessment of OSA in the hospital or home setting, using polygraphy, oximetry or contactless sleep monitoring.
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OBJECTIVE: To investigate the neurodevelopmental outcomes for preterm infants born < 29 weeks gestation with/without bronchopulmonary dysplasia (BPD). STUDY DESIGN: Preterm infants < 29 weeks' gestation born 2007-2018 in New South Wales and the Australian Capital Territory, Australia, were included. Infants who died < 36 weeks' postmenstrual age and those with major congenital anomalies were excluded. Subjects were assessed at 18-42 months corrected age using the Bayley Scales of Infant Development, 3rd edition. RESULTS: 1436 infants without BPD (non-BPD) and 1189 infants with BPD were followed. The BPD group, 69 % infants were discharged without respiratory support (BPD1), 29 % on oxygen (BPD2) and 2 % on pressure support/tracheostomy (BPD3). Moderate neurodevelopmental impairment (NDI) was evident in 5.7 % of non-BPD infants, 11 % BPD1, 15 % BPD2, 15 % BPD3 infants. Severe NDI was seen in 1.7 % non-BPD infants, 3.4 % BPD1, 7.3 % BPD2, 35 % BPD3 infants. After adjusting for confounders, infants with BPD2 (OR 2.24, 99.9 % CI 1.25 to 5.77) or BPD3 (OR 5.99, 99.9 % CI 1.27 to 46.77) were more likely to have moderate-severe NDI compared to non-BPD infants. CONCLUSION: The majority of infants with BPD were discharged home without respiratory support and had better neurocognitive outcomes in early childhood compared to those that required home-based oxygen or respiratory support.
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Displasia Broncopulmonar , Lactente Extremamente Prematuro , Humanos , Displasia Broncopulmonar/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Recém-Nascido , New South Wales/epidemiologia , Lactente , Pré-Escolar , Território da Capital Australiana/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Idade Gestacional , Desenvolvimento InfantilRESUMO
Melioidosis is a tropical infectious disease caused by the saprophytic gram-negative bacterium Burkholderia pseudomallei. Despite the infection being endemic in southeast Asia and northern Australia, the broad clinical presentations and diagnostic difficulties limit its early detection, particularly in children. Melioidosis more commonly affects the immunocompromised and adults. Melioidosis is increasingly being diagnosed around the world and whole-genome sequencing indicates that these cases are not linked with travel to endemic areas. Research has concentrated on the adult population with limited experience reported in the care of this uncommon, but potentially fatal condition in children presenting with bacteraemia and pneumonia.
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Burkholderia pseudomallei , Melioidose , Melioidose/diagnóstico , Humanos , Criança , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/isolamento & purificação , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Bacteriemia/diagnósticoRESUMO
BACKGROUND: Since 2010, most tertiary care hospitals in Australia have changed how they care for extremely premature infants. However, in-hospital and longer-term outcome data have suggested unchanged or even worse health outcomes in later epochs, especially respiratory outcomes. This study examined the trend in outcomes since these changes were introduced, particularly the prevalence of chronic neonatal lung disease (CLD). METHODS: This is a retrospective cross-sectional analysis of data from the Neonatal Intensive Care Units' (NICUS) database of all perinatal intensive care units in New South Wales and the Australian Capital Territory, including infants born at ≥ 24 and ≤ 28 weeks of gestational age in tertiary perinatal units between January 1, 2010, and December 31, 2020. Temporal trends and changes in primary outcome were examined by linear and adjusted multivariable logistic regression models. RESULTS: This study included 3258 infants. We saw significant changes in antenatal magnesium sulfate (75% increase), delayed cord clamping (66% increase), delivery room intubations (30% decrease), any time (20% decrease), duration on mechanical ventilation (100-hour decrease), and hours on noninvasive ventilation (200-hour increase). Mortality decreased from 17% to 6%. The incidence of CLD increased significantly even when adjusted for confounders (15% increase). Any time and mean hours spent on mechanical ventilation significantly increased the odds of CLD. This study could not find a significant association of any of the protective antenatal treatments on CLD. CONCLUSIONS: The last decade saw a significant improvement in survival and survival to discharge without major morbidity. There was increased use of magnesium sulfate, delayed cord clamping, and less invasive respiratory management of extremely preterm infants. The avoidance of mechanical ventilation may impact the incidence of CLD.
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Lactente Extremamente Prematuro , Pneumopatias , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , New South Wales/epidemiologia , Território da Capital Australiana/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Sulfato de Magnésio , AustráliaRESUMO
BACKGROUND: Pulmonary exacerbations in cystic fibrosis (CF) significantly impact morbidity and mortality. This study aimed to assess treatment response rates and identify contributing factors towards treatment response. METHODS: In this single-center, retrospective, longitudinal study spanning four years, we analyzed all pulmonary exacerbation admissions. We compared lung function at baseline, admission, end of treatment, and 6-week follow-up. Treatment response was defined as ≥95% recovery of baseline FEV
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Pulmonary fibrosis (PF) in children is a rare complication of specific forms of childhood interstitial lung diseases (chILD) with extremely limited scientific evidence to guide optimal management. Whilst there continues to be significant progress in PF management for adult populations, paediatric guidelines have stagnated. New anti-fibrotic medications (nintedanib and pirfenidone) are finding regular use amongst adult PF patients but remain largely unstudied and untested in children. Although there are major differences between the two age-group populations, it is useful to learn from the evolution of adult PF management, especially in the absence of dedicated paediatric studies. Whilst there have been recent trials aimed at assessing the safety and efficacy of drugs such as nintedanib and hydroxychloroquine, there is still a dire need for more research aimed at further assessing current treatment practices and evaluating the safety and efficacy of new emerging treatments in the paediatric population.
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Highly effective modulator therapies (HEMTs) have revolutionised the management approach of most patients living with cystic fibrosis (CF) who have access to these therapies. Clinical trials have reported significant improvements across multiorgan systems, with patients surviving longer. However, there are accumulating case reports and observational data describing various adverse events following initiation of HEMTs including drug-to-drug interactions, drug induced liver injury, Stevens-Johnson syndrome, and neurocognitive symptoms including psychosis and depression, which have required discontinuation of therapy. Current clinical trials are assessing efficacy in younger patients with CF, yet long-term studies are also required to better understand the safety profile in the real-world setting across all ages and the impact of HEMT dose alteration or discontinuation.
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Fibrose Cística , Humanos , Fibrose Cística/tratamento farmacológico , Cognição , Regulador de Condutância Transmembrana em Fibrose Cística , Mutação , Aminofenóis , Agonistas dos Canais de CloretoRESUMO
Poor adherence is an important factor in unstable disease control and treatment failure. There are multiple ways to monitor a patient's adherence, each with their own advantages and disadvantages. The reasons for poor adherence are multi-factorial, inter-related and often difficult to target for improvement. Although practitioners can implement different methods of adherence, the ultimate aim is to improve health outcomes for the individual and the health care system. Asthma is a common airway disease, particularly diagnosed in children, often treated with inhaled corticosteroids and long-acting bronchodilators. Due to the disease's tendency for exacerbations and consequently, when severe will require unscheduled health care utilisation including hospital admissions, considerable research has been done into the effects of medication adherence on asthma control. This review discusses the difficulties in defining adherence, the reasons for and consequences of poor adherence, and the methods of recording and improving adherence in asthma patients, including an in-depth analysis of the uses of smart inhalers.
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Cough medicines have been in use for over a century to treat the common and troublesome, but often helpful, symptoms of cough in children. They contain various combinations of "anti-tussive" drugs including opioids, antihistamines, herbal preparations, mucolytics, decongestants and expectorants. Whilst theoretically attractive for symptom relief when children are suffering, as time has passed these popular over the counter medicines have been shown to lack efficacy, delay more serious underlying diagnoses, and can cause complications and sometimes death. This has resulted in clinician concerns, a citizen petition to the American Food and Drug Association in 2007, some self-regulation from manufacturers and escalating restrictions on their use from regulatory agencies across the world over the last twenty years. This article will review the protective role of cough, juxtapose the conflicting treatment goals of suppressing a dry cough and promoting expectoration for a wet cough, consider the evidence basis for prescribing cough medicines in comparison to other more specific treatments such as for asthma [beta agonists] or infection [antibiotics], regulatory interventions, and conclude with the view that over counter cough medicines should not be used in children, especially young children.
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Antitussígenos , Criança , Humanos , Pré-Escolar , Antitussígenos/uso terapêutico , Tosse/tratamento farmacológico , Tosse/etiologia , Expectorantes/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Medicamentos sem Prescrição/uso terapêuticoRESUMO
Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4+ T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4+ T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus. This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4+ T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.
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BACKGROUND: Respiratory infections caused by Staphylococcus aureus and Pseudomonas aeruginosa are a major concern for cystic fibrosis (CF) patients due to increasing antibiotic resistance. Bacteriophages, which are viruses that selectively target and kill bacteria, are being studied as an alternative treatment for these infections. This systematic review evaluates the safety and effectiveness of bacteriophages for the treatment of CF-related infections caused by S. aureus and/or P. aeruginosa. We conducted a search for original, published articles in the English language up to March 2023. Studies that administered bacteriophages via intravenous, nebulised, inhaled, or intranasal routes were included, with no comparators required. In vitro and in vivo studies were eligible for inclusion, and only animal in vivo studies that utilised a CF transmembrane conductance regulator (CFTR) animal model were included. Bacteriophage treatment resulted in a decrease in bacterial load in both humans and animals infected with P. aeruginosa. Complete eradication of P. aeruginosa was only observed in one human subject. Additionally, there was a reduction in biofilm, improvement in resistance profile, and reduced pulmonary exacerbations in individual case reports. Evidence suggests that bacteriophage therapy may be a promising treatment option for CF-related infections caused by P. aeruginosa and S. aureus. However, larger and more robust trials are needed to establish its safety and efficacy and create necessary evidence for global legislative frameworks.