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Long-term effects of early, recurrent human exposure to general anaesthesia remain unknown. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial provided an opportunity to examine this issue in children randomly assigned in infancy to either repeated bronchoalveolar-lavage (BAL)-directed therapy with general anaesthesia or standard care with no planned lavages up to 5 years of age when all children received BAL-directed therapy under general anaesthesia. This multicentre, randomised, open-label phase 4 trial (CF-GAIN) used the original ACFBAL trial randomisation at 3·6 months (SD 1·6) to BAL-directed therapy or standard-care groups to assess the impact of general anaesthesia exposures over early childhood. Children who completed the ACFBAL trial, with a mean age of 5·1 (SD 0·18) years, received standardised neurobehavioural and health-related-quality-of-life assessment and brain MRI scans between Oct 8, 2013, and June 30, 2017, at a mean age of 12·8 (SD 1·7) years at three hospitals in Australia and one hospital in New Zealand. The primary outcome was a composite score of performance on a standardised, computer-based assessment of child attention, processing speed, and response inhibition skills (Conners Continuous Performance test, second edition). Secondary outcomes included intellectual function, other neurobehavioural measures, and brain imaging as an exploratory outcome. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000057785) and is completed. At 2 years, the BAL-directed therapy group (n=52) and standard-care group (n=45) had a median of 2·0 (IQR 1·0–3·0) and 0·0 (0·0–0·0) exposures, respectively. At completion of the ACFBAL trial, the BAL-directed therapy group had a median of 6·0 (4·0–9·5) exposures and the standard-care group 2·0 (1·0–4·0) exposures. At CF-GAIN completion, the BAL-directed therapy group had a median of 10·0 (IQR 6·5–14·5) exposures and the standard-care group 4·0 (3·0–7·0) exposures. Cumulative general anaesthesia exposure time was not prospectively collected but, for those with complete cumulative exposure time data to the end of the ACFBAL trial, the median cumulative exposure time for the BAL-directed therapy group (n=29) was 180 (IQR 140–285) min and for the standard-care group (n=32) was 48 (30–122) min. The mean Conners Continuous Performance test, second edition composite score was 51 (SD 8·1) in BAL-directed therapy group and 53 (8·8) in the standard-care group; difference –1·7 (95% CI –5·2 to 1·7; p=0·32) with similar performance on other neurobehavioural measures, including measures of executive function, intellectual quotient scores, and brain imaging. Our findings suggest that repeated general anaesthesia exposure in young children with cystic fibrosis is not related to functional impairment in attention, intellectual quotient, executive function, or brain structure compared with a group with fewer and shorter cumulative anaesthesia durations. National Health and Medical Research Council Australia, Queensland Government Health Service and Clinical Innovation Fellowship, and the Children's Hospital Foundation Queensland. [ABSTRACT FROM AUTHOR]

Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung disease as captured on chest CT scans. A phase three, randomised, double-blind, placebo-controlled trial was done at eight paediatric cystic fibrosis centres in Australia and New Zealand. Infants (aged 3–6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria included prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or comorbidities other than cystic fibrosis, or macrolide hypersensitivity. Participants were randomly assigned (1:1) to receive either azithromycin (10 mg/kg bodyweight orally three times per week) or matched placebo until age 36 months. Randomisation was done with a permuted block strategy and an interactive web-based response system, stratified by study site. Unblinding was done once all participants completed the trial. The two primary outcomes were the proportion of children with radiologically defined bronchiectasis, and the percentage of total lung volume affected by disease. Secondary outcomes included clinical outcomes and exploratory outcomes were inflammatory markers. Analyses were done with the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT01270074). Between June 15, 2012, and July 10, 2017, 281 patients were screened, of whom 130 were enrolled, randomly assigned, and received first study dose. 68 participants received azithromycin and 62 received placebo. At 36 months, 88% (n=50) of the azithromycin group and 94% (n=44) of the placebo group had bronchiectasis (odds ratio 0·49, 95% CI 0·12 to 2·00; p=0·32), and total airways disease did not differ between groups (median difference −0·02%, 95% CI −0·59 to 0·56; p=0·96). Secondary outcome results included fewer days in hospital for pulmonary exacerbations (mean difference −6·3, 95% CI −10·5 to −2·1; p=0·0037) and fewer courses of inhaled or oral antibiotics (incidence rate ratio 0·88, 95% CI 0·81 to 0·97; p=0·0088) for those in the azithromycin group. For the preplanned, exploratory analysis, concentrations of airway inflammation were lower for participants receiving azithromycin, including interleukin-8 (median difference −1·2 pg/mL, 95% CI −1·9 to −0·5; p=0·0012) and neutrophil elastase activity (−0·6 μg/mL, −1·1 to −0·2; p=0·0087) at age 36 months, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months. There was no effect of azithromycin on body-mass index at age 36 months (mean difference 0·4, 95% CI −0·1 to 0·9; p=0·12), nor any evidence of pathogen emergence with the use of azithromycin. There were few adverse outcomes with no differences between the treatment groups. Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with cystic fibrosis lung disease. Therefore we suggest thrice-weekly azithromycin is a strategy that could be considered for the routine early management of paediatric patients with cystic fibrosis. Cystic Fibrosis Foundation. [ABSTRACT FROM AUTHOR]

Evidence shows that dialogic book-sharing improves language development in young children in low-middle income countries (LMICs), particularly receptive and expressive language. It is unclear whether this intervention also boosts development of other neurocognitive and socio-emotional domains in children. Using a randomized controlled trial (RCT) nested in the Drakenstein Child Health Study (DCHS), a book-sharing intervention was implemented in caregivers of 3.5-year-old preschool children living in low-income South African communities. 122 Caregivers and their children (mean age 3.5 years) were randomly assigned to an intervention group (n = 61) or waitlist control group (n = 61). A neurocognitive battery determined baseline receptive and expressive language, executive function, theory of mind, and behavior scores. No differences were observed between intervention and control groups on receptive and expressive language, or any of the neurocognitive or socio-emotional measures from baseline (3.5 years) to 4 months post-intervention administration (4 years). The benefits noted in prior literature of book-sharing in infants did not appear to be demonstrated at 4 months post-intervention, in children from 3.5 to 4 years of age. This suggests the importance of early intervention and emphasizes the need for further research on adaptation of book-sharing for older participants in a South African context. Trial registration : retrospectively registered on 03/04/2022 PACTR202204697674974. • A book-sharing intervention was administered in a South African birth cohort. • Neurocognitive and socioemotional variables were measured pre- and post-intervention. • No differences were found between intervention and control groups on measures. • Findings highlight the importance of early intervention. [ABSTRACT FROM AUTHOR]

Importance: Maternal postnatal depression (PND) is common and associated with adverse child outcomes. These effects are not inevitable, and it is critical to identify those most at risk. Previous work suggests that the risks of adverse outcomes are increased when PND is severe and persistent, but this has not been systematically studied.Objective: To examine the association between differing levels of persistence and severity of PND and long-term child outcomes.Design, Setting, and Participants: The sample for this observational study comprised participants in the Avon Longitudinal Study of Parents and Children in the United Kingdom. Three thresholds of PND severity-moderate, marked, and severe-were defined using the self-rated Edinburgh Postnatal Depression Scale (EPDS). Depression was defined as persistent when the EPDS score was above the threshold level at both 2 and 8 months after childbirth. For each of these severity and persistence categories, the following were examined: (1) the trajectories of later EPDS scores (6 time points between 21 months and 11 years after childbirth) and (2) child outcomes-behavioral problems at 3.5 years of age, school-leaving mathematics grades at 16 years of age, and depression at 18 years of age. Data analysis was conducted from July 12, 2016, to February 8, 2017.Main Outcomes and Measures: Child behavioral problems at 3.5 years of age using the Rutter total problems scale, school-leaving mathematics grades at 16 years of age extracted from records of external national public examinations, and offspring depression at 18 years of age using the Clinical Interview Schedule-Revised.Results: For the 9848 mothers in the sample, the mean (SD) age at delivery was 28.5 (4.7) years. Of the 8287 children, 4227 (51%) were boys and 4060 (49%) were girls. Compared with women with PND that was not persistent and women who did not score above the EPDS threshold, for all 3 severity levels, women with persistent PND showed elevated depressive symptoms up to 11 years after childbirth. Whether persistent or not, PND doubled the risk of child behavior disturbance. The odds ratio (OR) for child behavioral disturbance for mothers with moderate PND was 2.22 (95% CI, 1.74-2.83), for mothers with marked PND was 1.91 (95% CI, 1.36-2.68), and for mothers with severe PND was 2.39 (95% CI, 1.78-3.22). Persistence of severe PND was particularly important to child development, substantially increasing the risk for behavioral problems at 3.5 years of age (OR, 4.84; 95% CI, 2.94-7.98), lower mathematics grades at 16 years of age (OR, 2.65; 95% CI, 1.26-5.57), and higher prevalence of depression at 18 years of age (OR, 7.44; 95% CI, 2.89-19.11).Conclusions and Relevance: Persistent and severe PND substantially raises the risk for adverse outcome on all child measures. Meeting criteria for depression both early and late in the postnatal year, especially when the mood disturbance is severe, should alert health care professionals to a depression that is likely to be persistent and to be associated with an especially elevated risk of multiple adverse child outcomes. Treatment for this group should be prioritized. [ABSTRACT FROM AUTHOR]

This paper investigates the determinants of the corporate credit spreads changes in the Japanese bond markets. We show that the business cycle risk and market skewness risk affect changes in the credit spread in Japan even after controlling for the frequently used variables. We also find that the magnitude of market skewness risk is relatively higher for low-rated bonds. Our results are robust to changes in credit ratings, different maturity groups and time periods around the recent global financial crisis. [ABSTRACT FROM AUTHOR]

Background: Modern living is awash with low-frequency electromagnetic radiation raising concern over health effects, birth defects, and infant cancers especially leukemias. Medical/scientific opinion is ambivalent, especially regarding possible mechanisms of action despite our bodies׳ many electric currents.Aims: Are some cancers induced by morphogenetic changes rather than direct mutation? We wished to see if morphogenetic effects of weak, extremely low-frequency electric (ELF) fields in embryonated hen׳s eggs could induce cancers, knowing that such treatment is usually deleterious. We report a pilot study intended to reveal a promising cell source in which to search for cancer cells by established methods and then to check for DNA damage.Methods: Stored (5°C for 1-36 days) fresh, fertile hens׳ eggs were incubated (38°C, total five or six days) in presence or absence of a weak ELF oscillating electric field (1-40V/cm, 1-50Hz and two to six days). Separated embryos were assessed for development stage.Results: Storage of untreated eggs (>12 days, 5°C) allows a steady loss of normal embryo formation at 38°C (few viable by 25 days, half-life ~18 days). Surprisingly, incubation in a weak ELF field during the period of declining viability significantly (P: 0.03-0.0001) improved viability and condition of the embryos (new half-life ~21 days), rather than the expected converse. Thus for a few days, the field could keep viable some embryos that would otherwise not have survived.Conclusions: The rescued embryos and their untreated controls seem the most promising place to seek any carcinogenic effects of ELF fields. The nature of the presumed critical component keeping them viable during 5°C storage is at least of equal interest. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions. Study design: Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. Results: Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27 782 to 31 586, P = .90). Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35 252 to 16 676, P = .48). Conclusions: BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings. [ABSTRACT FROM AUTHOR]

The article presents a research study that seeks to describe the demographics, clinical features and outcomes among 2,986 patients with cystic fibrosis (CF) and to estimate incidence of the disease through a cross-sectional analysis of data from the Cystic Fibrosis Data Registry for 2009. Results show that CF remains a progressive respiratory disease associated with multisystem complications and better treatment in adolescence and early adulthood is required to further improve patient survival.

Summary: The exact incidence of paediatric primary spontaneous pneumothorax (PSP) is unclear, although PSP incidence in the general population is between 6 and 18 per 100000. PSP has been reported throughout the paediatric age range. A potential genetic predisposition for familial cases has been recently identified. Whilst there is universal consensus on the management of tension pneumothorax, lack of agreement and consistency exists across a wide range of management issues for other aspects of PSP management. Paediatric PSP may have a higher recurrence rate than adult PSP, and the presence of apical lung cysts or bullae is not predictive of recurrence. The decision for surgical intervention should be based on documented recurrence. There is a lack of paediatric evidence to guide management decisions, and extrapolation of predominantly adult data to younger age groups should not be encouraged. Given the relatively low apparent incidence, a multicentre approach to future research is required in order to generate the evidence required for informed management of PSP in children. [Copyright &y& Elsevier]

The article reports on a study which examines the nutritional status of zero- to 71-month-old children and their caregivers, as well as their socio-demographics in two provinces in South Africa. The study has used a structured questionnaire to collect information on socio-demographics, household food security, food consumption, maternal knowledge of nutrition and breast-feeding practices. The anthropometric measurements of the zero- to 71-month-old children and their caregivers were taken in light clothing and without shoes. The study shows that the prevalence of childhood malnutrition doubled from the first to second year of life and reached high levels in the Eastern Cape and KwaZulu-Natal. The study also shows that many of the caregivers were either overweight or obese.

Summary: High-resolution computed tomography (HRCT) scanning of the chest should not be considered a routine clinical investigation in the management of CF. Although it demonstrates the detection of early lung damage in children with cystic fibrosis (CF), before HRCT can be considered for routine clinical use in CF it needs to be shown that the benefit from the information obtained will out-weigh potential risks. There is insufficient evidence for the benefit of HRCT for its inclusion into routine care. Moreover, in the absence of information resulting in change in management, HRCT has the potential to increase anxiety for both clinicians and families. In order to advocate for incorporating this technology into routine CF care, further support for its role in management decisions is needed. [Copyright &y& Elsevier]

Summary: Background: Lower airway colonisation with Aspergillus fumigatus and the complicating hypersensitivity reaction allergic bronchopulmonary aspergillosis (ABPA) is well recognised in patients with cystic fibrosis (CF). There is a wide range in reported prevalence of ABPA in CF. Differences in predisposing factors such as atopy and climatic humidity, but also differences in reporting may in part explain this observation. In the Australian population there is a high frequency of atopy and the climate is relatively humid. Patients and methods: Children and adolescents with CF from the CF Clinic, Children''s Hospital at Westmead, Sydney, Australia were included in a retrospectively conducted study of Aspergillus colonisation and ABPA (1998–2003). Results: The prevalence of Aspergillus colonised patients increased significantly from 7.4% in 1998 to 18.8% in 2002. No seasonal variation in initial positive Aspergillus culture or in humidity was observed. A total of 13 patients (4.7%) were diagnosed with ABPA over the study period, with a significant increase in prevalence from 0.3% in 1998 to 4.0% in 2002. In addition, the criteria used for reporting ABPA in the study population were in agreement with the recently published diagnostic criteria for ABPA in CF. Conclusions: In spite of a high frequency of atopy and a relatively humid climate in the Sydney area, Aspergillus colonisation and ABPA in CF patients was not disproportionate. Moreover, criteria for reporting of ABPA in this setting was not different from that in the Northern Hemisphere. [Copyright &y& Elsevier]