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45 per patient-year in the simvastatin group and 1.9 in the placebo group (IRR 0.77, 95% CI 0.60 to 0.99).We found no effect on quality of life, lung function, 6-minute walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29).In our single-center RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.

Combined assessment of cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), and lung cancer (LC) may improve the effectiveness of LC screening in smokers. The aims were to derive and assess risk models for predicting LC incidence, CVD mortality, and COPD mortality by combining quantitative CT measures from each disease, and to quantify the added predictive benefit of self-reported patient characteristics given the availability of a CT scan.

A survey model (patient characteristics only), CT model (CT information only), and final model (all variables) were derived for each outcome using parsimonious Cox regression on a sample from the National Lung Screening Trial (n=15 000). Validation was performed using Multicentric Italian Lung Detection data (n=2287). Time-dependent measures of model discrimination and calibration are reported.

Age, mean lung density, emphysema score, bronchial wall thickness, and aorta calcium volume are variables which contributed to all final models. Nodule her model individually (survey model=87·5%, 84·3-90·6%; CT model=87·9%, 84·8-91·0%), but no external validation was performed due to a very low event frequency.

CT measures of CVD and COPD provides small but reproducible improvements to nodule-based LC risk prediction accuracy from 3 years' onwards. Self-reported patient characteristics may not be of added predictive value when CT information is available.

CT measures of CVD and COPD provides small but reproducible improvements to nodule-based LC risk prediction accuracy from 3 years' onwards. Self-reported patient characteristics may not be of added predictive value when CT information is available.

Lung ultrasound (LUS) is feasible for assessing lung injury caused by COVID-19. However, the prognostic meaning and time-line changes of lung injury assessed by LUS in COVID-19 hospitalised patients, is unknown.

Prospective cohort study designed to analyse prognostic value of LUS in COVID-19 patients by using a quantitative scale (LUZ-score) during the first 72 h after admission. Primary endpoint was in-hospital death and/or admission to the intensive care unit. Total length of hospital stay, increase of oxygen flow or escalate medical treatment during the first 72 h, were secondary endpoints.

130 patients were included in the final analysis; mean age was 56.7±13.5 years. Time since the beginning of symptoms until admission was 6 days (4-9). Lung injury assessed by LUZ-score did not differ during the first 72 h (21 points [16-26] at admission

20 points [16-27] at 72 h; p=0.183). In univariable logistic regression analysis estimated PaO2/FiO2 (HR 0.99 [0.98-0.99]; p=0.027) and LUZ-score>22 points (5.45 (1.42-20.90); p=0.013) were predictors for the primary endpoint.

LUZ-score is an easy, simple and fast point of care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated PAFI) to further refine risk stratification.

LUZ-score is an easy, simple and fast point of care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated PAFI) to further refine risk stratification.Cues such as odours that do not per se evoke bronchoconstriction can become triggers of asthma exacerbations. Despite its clinical significance, the neural basis of this respiratory nocebo effect is unknown. We investigated this effect in a functional magnetic resonance imaging (fMRI) study involving 36 healthy volunteers. The experiment consisted of an Experience phase in which volunteers experienced dyspnea while being exposed to an odorous gas ("Histarinol"). Volunteers were told that "Histarinol" induces dyspnea by bronchoconstriction. This was compared to another odorous gas which did not evoke dyspnea. Actually, dyspnea was induced by a concealed, resistive load inserted into the breathing system. In a second, Expectation phase, Histarinol and the control gas were both followed by an identical, very mild load. Respiration parameters were continuously recorded and after each trial participants rated dyspnea intensity. Dyspnea ratings were significantly higher in Histarinol compared to control conditions, both in the Experience and in the Expectation phase, despite identical physical resistance in the Expectation phase. Insula fMRI signal matched the actual load, i.e. a significant difference between Histarinol and Control in the Experience phase, but no difference in the Expectation phase. The periaqueductal gray showed a significantly higher fMRI signal during the expectation of dyspnea. Finally, Histarinol related deactivations during the Expectation phase in the rostral anterior cingulate cortex mirror similar responses for nocebo effects in pain. These findings highlight the neural basis of expectation effects associated with dyspnea, which has important consequences for our understanding of the perception of respiratory symptoms.

for the management of patients referred to respiratory triage during the early stages of the SARS-CoV-2 pandemic, either chest radiograph (CXR) or computed tomography (CT) were used as first-line diagnostic tools. The aim of this study was to compare the impact on triage, diagnosis and prognosis of patients with suspected COVID-19 when clinical decisions are derived from reconstructed CXR or from CT.

we reconstructed CXR (r-CXR) from high-resolution CT (HRCT) scan. Five clinical observers independently reviewed clinical charts of 300 subjects with suspected COVID-19 pneumonia, integrated with either r-CXR or HRCT report in two consecutive blinded and randomised sessions clinical decisions were recorded for each session. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and prognostic value were compared between r-CXR and HRCT. The best radiological integration was also examined to develop an optimised respiratory triage algorithm.

interobserver agreement was faibles that were similarly linked to mortality by adjusted multivariable models CONCLUSIONS the present findings suggest that clinical triage is safely assisted by CXR. An integrated algorithm using first-line CXR and contingent use of HRCT can help optimise management and prognostication of COVID-19.Nuclear Argonaute proteins, guided by their bound small RNAs to nascent target transcripts, mediate cotranscriptional silencing of transposons and repetitive genomic loci through heterochromatin formation. The molecular mechanisms involved in this process are incompletely understood. Here, we show that the SFiNX complex, a silencing mediator downstream from nuclear Piwi-piRNA complexes in Drosophila, facilitates cotranscriptional silencing as a homodimer. The dynein light chain protein Cut up/LC8 mediates SFiNX dimerization, and its function can be bypassed by a heterologous dimerization domain, arguing for a constitutive SFiNX dimer. Dimeric, but not monomeric SFiNX, is capable of forming molecular condensates in a nucleic acid-stimulated manner. Mutations that prevent SFiNX dimerization result in loss of condensate formation in vitro and the inability of Piwi to initiate heterochromatin formation and silence transposons in vivo. We propose that multivalent SFiNX-nucleic acid interactions are critical for heterochromatin establishment at piRNA target loci in a cotranscriptional manner.The emergence of next-generation genomic sequencing (NGS) tests for use in clinical care has generated widespread interest around the globe, but little is known about the availability and funding of these tests worldwide. We examined NGS availability across world regions and countries, with a particular focus on availability of three key NGS tests-Whole-Exome Sequencing or Whole-Genome Sequencing for diagnosis of suspected genetic diseases such as intellectual disability disorders or rare diseases, non-invasive prenatal testing for common genetic abnormalities in fetuses and tumor sequencing for therapy selection and monitoring of cancer treatment. We found that these NGS tests are available or becoming available in every major region of the world. This includes both high-income countries with robust genomic programmes such as the USA and the UK, and growing availability in countries with upper-middle-income economies. We used exploratory case studies across three diverse health care systems (publicly funded/national (UK), publicly funded/provincial (Canada) and mixed private/public system (USA)) to illustrate the funding challenges and approaches used to address those challenges that might be adopted by other countries. We conclude by assessing what type of data and initiatives will be needed to better track and understand the use of NGS around the world as such testing continues to expand.

Employees working in the welfare and healthcare industry have poorer mental health than other occupational groups; however, there has been little examination of suicide among this group. In this study, we examined suicide rates among welfare support workers and compared them to other occupations in Australia.

We used data from the National Coroners Information System to obtain suicide deaths between the years 2001 and 2016. Using the Australian standard population from 2001 and Census data from 2006, 2011 and 2016, we calculated age-standardised suicide rates and rate ratios to compare suicide rates across different occupational groups.

Overall, the age-standardised suicide rate of welfare support workers was 8.6 per 100 000 people. The gender-stratified results show that male welfare support workers have a high suicide rate (23.8 per 100 000 people) which is similar to male social workers and nurses (25.4 per 100 000). After adjusting for age and year of death, both males (rate ratio 1.48, 95% CI 1.23 to 1.78) and female welfare support workers (rate ratio 1.49, 95% CI 1.20 to 1.86) have higher suicide rate ratios compared with the reference group (excluding occupations from the comparison groups).

The age-standardised suicide rates of male welfare support workers are comparable to occupations which have been identified as high-risk occupations for suicide. Both female and male welfare support workers are at elevated risk of suicide compared with other occupations. Further research is required to understand the drivers of the elevated risk in this group.

The age-standardised suicide rates of male welfare support workers are comparable to occupations which have been identified as high-risk occupations for suicide. Both female and male welfare support workers are at elevated risk of suicide compared with other occupations. Further research is required to understand the drivers of the elevated risk in this group.

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