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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