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Aims: Despite evidence of hemodynamic benefit of sodium nitroprusside (SNP) treatment for acute heart failure (AHF), there are limited data about its efficacy and safety. This study aimed to assess the effectiveness and safety of SNP treatment, to explore the impact of N-terminal pro-B natriuretic peptide (NT-proBNP) reduction on clinical endpoints and to identify possible predictors of clinical response. Methods and results: Multicenter retrospective cohort study of 200 patients consecutively admitted for AHF in 2 Italian Centers. Primary endpoint was the reduction of NT-proBNP levels ≥25% from baseline values within 48 h from the onset of SNP infusion. Secondary and safety endpoints included all-cause mortality, rehospitalization for HF at 1, 3 and 6 months, length of hospital stay (LOS) and severe hypotension. 131 (66%) patients experienced a NT-proBNP reduction ≥25% within 48 h from treatment onset, irrespective of initial systolic blood pressure (SBP). Left ventricular end diastolic diameter (LVEDD) was the only independent predictor of treatment efficacy. Patients who achieved the primary endpoint (i.e., ‘responders’) had lower LOS (median 15 [IQR:10–27] vs 19 [IQR:12–35] days, p-value = 0.033) and a lower incidence of all-cause mortality and rehospitalization for HF at 1 and 3 months compared to “non responders” (p-value <0.050). Severe hypotension was observed in 10 (5%) patients, without any adverse clinical consequence. Conclusion: SNP is a safe and effective treatment of AHF, particularly in patients with dilated left ventricle. Reduced NT-proBNP levels in response to SNP is associated to shorter LOS and lower risk of 1- and 3-month re-hospitalizations for HF. Clinical trial registration. http://www.clinicaltrials.gov. Unique identifier: NCT05027360

Background: Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods: We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age- and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation. Findings: We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries’ COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries’ income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well

Individuals with Prader-Willi syndrome (PWS) often have excessive daytime sleepiness and emotional/behavioral disturbances. The objective of this study was to examine whether daytime sleepiness was associated with these emotional/behavioral problems, independent of nighttime sleep-disordered breathing, or the duration of sleep. Caregivers of individuals with PWS (aged 3 to 25 years) completed the Pediatric Sleep Questionnaire (PSQ), Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the parent version of the Developmental Behavior Checklist (DBC-P). Sleep adequacy was adjusted for age by computing sleep duration against age-specific recommendations. The associations between ESS-CHAD and the total DBC and its subscale scores were evaluated by linear regression, adjusted for sleep-related breathing difficulties, sleep adequacy, and body mass index (BMI). There were 54 responses for individuals with PWS (including 22 males) aged 4.4-24.0 (mean 12.5) years. Daytime sleepiness predicted a substantial proportion of the variance in total DBC-P scores in the unadjusted model (28%; beta = 0.028; p < 0.001) and when adjusted for sleep adequacy, BMI, and sleep-related breathing difficulties (29%; beta = 0.023; p = 0.007). This relationship was not moderated by BMI Z-scores, but the relationship was more prominent for children younger than 12 years than for children older than 12 years. Conclusion(s): These findings provide preliminary novel evidence that daytime sleepiness may drive the expression of emotional/behavioral disturbances, and should be explored as a potential modifiable risk factor for these disturbances in PWS, particularly pre-adolescent children.Copyright © 2022, The Author(s).

OBJECTIVE: 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. METHODS: 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). RESULTS: Parents' (T1, n=19; T2, n=17) HRQoL was lower than population norms. Study satisfaction (T1) and perceived understanding (T2) were positively correlated (rs=0.68, p=0.014). Satisfaction with information (T1 and T2) and decisional regret (T2) were negatively correlated (T1 rs=-0.71, p=0.01; T2 rs=-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. CONCLUSIONS: 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.

BACKGROUND: 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. RESULTS: 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/pathogenic 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. CONCLUSIONS: 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.

BACKGROUND: Existing evidence suggests that some individuals from ethnic minority backgrounds are at increased risk of suicide compared to their majority ethnic counterparts, whereas others are at decreased risk. We aimed to estimate the absolute and relative risk of suicide in individuals from ethnic minority backgrounds globally. METHODS: Databases (Medline, Embase, and PsycInfo) were searched for epidemiological studies between 01/01/2000 and 3/07/2020, which provided data on absolute and relative rates of suicide amongst ethnic minority groups. Studies reporting on clinical or specific populations were excluded. Pairs of reviewers independently screened titles, abstracts, and full texts. We used random effects meta-analysis to estimate overall, sex, location, migrant status, and ancestral origin, stratified pooled estimates for absolute and rate ratios. PROSPERO registration: CRD42020197940. FINDINGS: A total of 128 studies were included with 6,026,103 suicide deaths in individuals from an ethnic minority background across 31 countries. Using data from 42 moderate-high quality studies, we estimated a pooled suicide rate of 12·1 per 100,000 (95% CIs 8·4-17·6) in people from ethnic minority backgrounds with a broad range of estimates (1·2-139·7 per 100,000). There was weak statistical evidence from 51 moderate-high quality studies that individuals from ethnic minority groups were more likely to die by suicide (RR 1·3 95% CIs 0·9-1·7) with again a broad range amongst studies (RR 0·2-18·5). In our sub-group analysis we only found evidence of elevated risk for indigenous populations (RR: 2·8 95% CIs 1·9-4·0; pooled rate: 23·2 per 100,000 95% CIs 14·7-36·6). There was very substantial heterogeneity (I2 > 98%) between studies for all pooled estimates. INTERPRETATION: The homogeneous grouping of individuals from ethnic minority backgrounds is inappropriate. To support suicide prevention in marginalised groups, further exploration of important contextual differences in

Introduction/Aim. The Australian Bronchiectasis Registry (ABR), established in 2015, is a common nation-wide research platform to improve longitudinal data collection in children and adults with bronchiectasis unrelated to cystic fibrosis. Current descriptions of paediatric cohorts with bronchiectasis are largely unicentric and ABR is thus the leading paediatric cohort in Australia. Using ABR, we described the baseline characteristics of paediatric participants and sought to determine regional variations in this cohort. Methods. We analysed the baseline data of paediatric patients (<18 years) with radiologically confirmed bronchiectasis using ABRas centralised database. Results. From March 2016-August 2019, 496 children [222 females; 321 Indigenous; median age = 8 years (IQR 6-11)] were enrolled from 4 Australian sites. The aetiology was considered post-infectious in 70% of children, with 40% having had bronchiectasis for >5 years. Asthma (24%) was the most common reported co-morbidity and non-respiratory comorbidities were uncommon. Spirometry was available only in 21% of the cohort, with median FEV1 = 59.1% predicted (IQR 50.8-69.48), FVC = 66% (58.56-74.6). On CT chest, left (80%) and right (78%) lower lobes were the most common lobes affected, majority with cylindrical bronchiectasis, 6 children had cystic bronchiectasis. 6% children isolated Pseudomonas aeruginosa (PsA) from the lower airways, significantly higher proportion of these had Primary Ciliary Dyskinesia (PCD, 13.3% vs 2.1% in nonPsA; P < 0.001). Macrolide therapy was used in 43.5% of the cohort, with nearly a quarter of the group on short acting bronchodilator therapy. 244/488 (50%) children had at least 1 exacerbation requiring hospital an admission in the last 12 months, with exacerbations in 6.5% of the cohort treated with outpatient intra-venous antibiotic therapy. Conclusion. The largest cohort of Australian children with bronchiectasis has been described. Some regional differences exist in the

Aim: In children with Prader-Willi syndrome (PWS), growth hormone (GH) improves height and body composition; however, may be associated with worsening sleep-disordered breathing (SDB). Some studies have reported less SDB after GH initiation, but follow-up with polysomnography is still advised in most clinical guidelines. Method(s): This retrospective, multicentre study, included children with PWS treated with GH at seven PWS treatment centres in Australia over the last 18 years. A paired analysis comparing polysomnographic measures of central and obstructive SDB in the same child, before and after GH initiation was performed with Wilcoxon signed-rank test. The proportion of children who developed moderate/severe obstructive sleep apnoea (OSA) was calculated with their binomial confidence intervals. Result(s): We included 112 patients with available paired data. The median age at start of GH was 1.9 years (range 0.1-13.5 years). Median obstructive apnoea hypopnoea index (AHI) at baseline was 0.43/h (range 0-32.9); 35% had an obstructive AHI above 1.0/h. Follow-up polysomnography within 2 years after the start of GH was available in 94 children who did not receive OSA treatment. After GH initiation, there was no change in central AHI. The median obstructive AHI did not increase significantly (P = 0.13), but 12 children (13%, CI95% 7-21%) developed moderate/severe OSA, with clinical management implications. Conclusion(s): Our findings of a worsening of OSA severity in 13% of children with PWS support current advice to perform polysomnography after GH initiation. Early identification of worsening OSA may prevent severe sequelae in a subgroup of children.Copyright © 2021 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Introduction: In adults with bronchiectasis, multicentre data advanced the field including disease characterisation and derivation of phenotypes such as 'frequent exacerbator (FE)' (>=3 exacerbations/year). However, paediatric cohorts are largely limited to single centres and no scientifically derived phenotypes of paediatric bronchiectasis yet exists. Using paediatric data from the Australian Bronchiectasis Registry (ABR), we aimed to: (a) describe the clinical characteristics and compare Indigenous with non-Indigenous children, and (b) determine if a FE phenotype can be identified and if so, its associated factors. Method(s): We retrieved data of children (aged <18-years) with radiologically confirmed bronchiectasis, enrolled between March 2016-March 2020. Result(s): Across five sites, 540 children [288 Indigenous; median age = 8-years (IQR 6-11)] were included. Baseline characteristics revealed past infection/idiopathic was the commonest (70%) underlying aetiology, most had cylindrical bronchiectasis and normal spirometry. Indigenous children (vs. non-Indigenous) had significantly more environmental tobacco smoke exposure (84% vs 32%, p < 0.0001) and lower birth weight (2797 g vs 3260 g, p < 0.0001). FE phenotype present in 162 (30%) children, was associated with being younger (ORadjusted = 0.85, 95%CI 0.81-0.90), more recent diagnosis of bronchiectasis (ORadjusted = 0.67; 95%CI 0.60-0.75), recent hospitalization (ORadj = 4.51; 95%CI 2.45-8.54) and Pseudomonas aeruginosa (PsA) infection (ORadjusted = 2.43; 95%CI 1.01-5.78). The FE phenotype were less likely to be Indigenous (ORadjusted = 0.14; 95%CI 0.03-0.65). Conclusion(s): Even within a single country, the characteristics of children with bronchiectasis differ among cohorts. A paediatric FE phenotype exists and is characterised by being younger with a more recent diagnosis, PsA infection and previous hospitalization. Prospective data to consolidate our findings characterising childhood bronchiectasis phenotype

Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by neurodevelopmental delays, hyperphagia, difficulties with social communication and challenging behaviours. Individuals require intensive supervision from caregivers which may negatively affect caregiver quality of life. This study used data collected in the Australasian PWS Registry (n = 50, mean age 11.2 years) to evaluate associations between child behaviours and caregiver mental well-being. Symptoms of sleep-related breathing disorder, child depression and social difficulties were associated with poorer caregiver mental and physical well-being. Growth hormone therapy use was associated with better caregiver mental and physical well-being. Optimising management of problematic behaviours and sleep disturbances have the potential to support caregivers who are the most vital network of support for individuals affected by PWS.Copyright © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chronic neonatal lung disease (CNLD) is defined as continued need for any form of respiratory support (supplemental oxygen and/or assisted ventilation) beyond 36 weeks PMA. Low-flow supplemental oxygen facilitates discharge from hospital of infants with CNLD who are hypoxic in air and is widely used despite lack of evidence on the most appropriate minimum mean target oxygen saturations. Furthermore, there are minimal data to guide the home monitoring, titration or weaning of supplemental oxygen in these infants. The purpose of this position statement is to provide a guide for the respiratory management of infants with CNLD, with special emphasis on role and logistics of supplemental oxygen therapy beyond the NICU stay. Reflecting a variety of clinical practices and infant comorbidities (presence of pulmonary hypertension, retinopathy of prematurity and adequacy of growth), it is recommended that the minimum mean target range for SpO2 during overnight oximetry to be 93-95% with less than 5% of total recording time to be below 90% SpO2. Safety of short-term disconnection from supplemental oxygen should be assessed before discharge, with majority of infants with CNLD not ready for discharge until supplemental oxygen requirement is <=0.5 L/min. Sleep-time assessment of oxygenation with continuous overnight oximetry is recommended when weaning supplemental oxygen. Palivizumab is considered safe and effective for the reduction of hospital admissions with RSV infection in this group. This statement would be useful for paediatricians, neonatologists, respiratory and sleep physicians and general practitioners managing children with CNLD.Copyright © 2020 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.

ES is a 7-month-old female born to a non-consanguineous Caucasian couple at 35 weeks of gestation following a pregnancy that was complicated by Maternal Non-Hodgkin's Lymphoma requiring R-CHOP (Chemotherapy) from 17 to 35 weeks antenatally. At 12 weeks of age ES progressively deteriorated following a respiratory illness requiring invasive respiratory support. Initial investigations showed marked lymphopenia of 1.5 x 10^9/L and a search for opportunistic organisms revealed elevated Pneumocystis Jiroveci counts in her BAL. Following this she was started on a combination of Primaquine, Lincomycin and Bactrim treatment. Apart from the lymphopenia, her IgG was noted to be extremely low at <1.0 g/L. There were concerns of a primary immunodeficiency, however this was confounded by the possibility of a secondary immunodeficiency due to the use of maternal R-CHOP antenatally. Her recent thymic emigrants were noted to be 53% suggestive of adequate output from the thymus and her PHA was also normal suggestive of adequately functioning T cells. Recovery of lymphocyte counts to 7.2 x 109/L and IgG to 3.2 g/L post supportive management including intravenous immunoglobulin over the ensuing months confirmed the likelihood of a secondary immunodeficiency in her presentation. She is currently on low flow oxygen and her immunoglobulin levels have stabilized without ongoing IVIG, as her own production of immunoglobulins takes over. This case illustrates the importance of monitoring of babies born to mothers on chemotherapy and consideration of supportive management which may include antimicrobial prophylaxis and intravenous immunoglobulins during the first 6-12 months of life.