To investigate whether risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outcomes of coronavirus disease 2019 (covid-19) differed between adults living with and without children during the first two waves of the UK pandemic.

Population based cohort study, on behalf of NHS England.

Primary care data and pseudonymously linked hospital and intensive care admissions and death records from England, during wave 1 (1 February to 31 August 2020) and wave 2 (1 September to 18 December 2020).

Two cohorts of adults (18 years and over) registered at a general practice on 1 February 2020 and 1 September 2020.

Adjusted hazard ratios for SARS-CoV-2 infection, covid-19 related admission to hospital or intensive care, or death from covid-19, by presence of children in the household.

Among 9 334 392adults aged 65 years and under, during wave 1, living with children was not associated with materially increased risks of recorded SARS-CoV-2 infection, covid-19 related hospital or l admissions of 1-5 per 10 000 people, from 160 to between 161 and 165. Living with children aged 12-18 years was associated with an increase of 160-190 per 10 000 in the number of SARS-CoV-2 infections and an increase of 2-6 per 10 000 in the number of hospital admissions.

In contrast to wave 1, evidence existed of increased risk of reported SARS-CoV-2 infection and covid-19 outcomes among adults living with children during wave 2. However, this did not translate into a materially increased risk of covid-19 mortality, and absolute increases in risk were small.

In contrast to wave 1, evidence existed of increased risk of reported SARS-CoV-2 infection and covid-19 outcomes among adults living with children during wave 2. However, this did not translate into a materially increased risk of covid-19 mortality, and absolute increases in risk were small.With the increased use of acid suppressants, significant potential complications, such as community-acquired pneumonia are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and community-acquired pneumonia. Our main objective was to evaluate the risk of community-acquired pneumonia in children using acid suppressants (proton pump inhibitors and/or histamine-2-receptor antagonists).We performed a cohort study using data from the Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to 4 unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of community-acquired pneumonia. The cohort consisted of 84 868 exposed and 325 329 unexposed children.Current use of proton pump inhibitors and histamine-2-receptor antagonists was associated with an increased risk of community acquired pneumonia, adjusted hazard ratio 2.05 (95% CI 1.90 to 2.22) and 1.80 (95% CI 1.67 to 1.94), respectively. The risk was even greater in patients with respiratory disease. Long term use >211 days of proton pump inhibitors and histamine-2-receptor antagonists led to a significantly greater risk of community-acquired pneumonia compared to short term use less then 31 days. After cessation of therapy, the risk remained increased for the following 7 months.The use of acid suppressants in children was associated with a doubled risk of community-acquired pneumonia. This risk increased with chronic use, respiratory disease and remained increased after discontinuation of therapy.

Obstructive Sleep Apnoea (OSAS) causes intermittent hypoxia (IH) that in turn induces endothelial dysfunction and atherosclerosis progression. We hypothesized that VE-Cadherin cleavage, detected by its released extracellular fragment solubilised in the blood (sVE), may be an early indicator of emergent abnormal endothelial permeability. Our aim was to assess VE-cadherin cleavage in OSAS patients and in

and

IH models to decipher the cellular mechanisms and consequences.

Sera from 7 healthy volunteers exposed to fourteen nights of IH, 43 OSAS patients and 31 healthy control subjects were analysed for their sVE content. Human aortic endothelial cells (HAEC) were exposed to 6 h of IH

, with or without an antioxidant or inhibitors of HIF-1, tyrosine kinases or VEGF pathways. VE-Cadherin cleavage and phosphorylation were evaluated, and endothelial permeability was assessed by measuring trans-endothelial electrical resistance (TEER) and FITC-Dextran flux.

sVE was significantly elevated in sera from healthy volunteers submitted to IH and OSAS patients before treatment, but conversely, decreased in OSAS patients after 6 months of continuous positive airway pressure treatment. OSAS was the main factor accounting for sVE variations in a multivariate analysis. see more In

experiments, cleavage and expression of VE-Cadherin increased upon HAEC exposure to IH. TEER decreased and FITC-Dextran flux increased. These effects were reversed by all the pharmacological inhibitors tested.

We suggest that in OSAS, IH increases endothelial permeability in OSAS by inducing VE-Cadherin cleavage through ROS production and activation of HIF-1, VEGF and tyrosine kinase pathways.

We suggest that in OSAS, IH increases endothelial permeability in OSAS by inducing VE-Cadherin cleavage through ROS production and activation of HIF-1, VEGF and tyrosine kinase pathways.

The UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces re-consultation due to clinical deterioration in “at risk” children presenting with influenza-like illness (ILI) in primary or ambulatory care.

“At risk” children aged 6 months to 12 years presenting within f5 days of ILI onset were randomly assigned to oral co-amoxiclav 400/57 or placebo twice daily for 5 days (dosing based on age±weight). “At risk” groups included children with respiratory, cardiac, and neurological conditions. Randomisation was stratified by region and used a non-deterministic minimisation algorithm to balance age and current seasonal influenza vaccination status. Our target sample size was 650 children, which would have allowed us to detect a reduction in the proportion of children re-consulting due to clinical deterioration from 40% to 26% with 90% power and 5% two-tailed alpha error, including allowance for 25% lo CI 0.90 to 2.34). Sixty-six adverse events were reported in total (co-amoxiclav n=37, placebo n=29). Nine serious adverse events were reported per group; none were considered related to study medication.

Our trial did not find evidence that treatment with co-amoxiclav reduces risk of re-consultation due to clinical deterioration in “at risk” children who present early with ILI during influenza season. Our findings therefore do not support early co-amoxiclav use in children with seasonal ILI.

Our trial did not find evidence that treatment with co-amoxiclav reduces risk of re-consultation due to clinical deterioration in “at risk” children who present early with ILI during influenza season. Our findings therefore do not support early co-amoxiclav use in children with seasonal ILI.

Advanced non-malignant respiratory diseases are associated with significant patient morbidity, yet access to palliative care occurs late, if at all.

To examine referral criteria for palliative care among patients with advanced non-malignant respiratory disease, with a view to developing a standardised set of referral criteria.

Systematic review of all studies reporting on referral criteria to palliative care in advanced non-malignant respiratory disease, with a focus on chronic obstructive pulmonary disease and interstitial lung disease.

A systematic review conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses guideline was undertaken using electronic databases (Ovid, MEDLINE, Ovid Embase, and PubMed).

Searches yielded 2052 unique titles, which were screened for eligibility resulting in 62 studies addressing referral criteria to palliative care in advanced non-malignant respiratory disease. Of 18 categories put forward for referral to palliative care, the most commonly discussed factors were hospital use (69% of papers), indicators of poor respiratory status (47%), physical and emotional symptoms (37%), functional decline (29%), need for advanced respiratory therapies (27%), and disease progression (26%).

Clinicians consider referral to specialist palliative care for a wide range of disease- and needs-based criteria. Our findings highlight the need to standardise palliative care access by developing consensus referral criteria for patients with advanced non-malignant respiratory illnesses.

Clinicians consider referral to specialist palliative care for a wide range of disease- and needs-based criteria. Our findings highlight the need to standardise palliative care access by developing consensus referral criteria for patients with advanced non-malignant respiratory illnesses.The impact of blood eosinophil counts on the development of chronic obstructive lung disease (COPD) is unknown. We investigated whether a higher blood eosinophil counts was associated with the risk of developing obstructive lung disease (OLD) in a large cohort of men and women free lung disease at baseline.Cohort study of 359 456 Korean adults without a history of asthma and without OLD at baseline who participated in health screening exams including spirometry. OLD was defined as pre-bronchodilator FEV1/FVC less then 0.7 and FEV1 less then 80% predicted.After a median follow-up of 5.6 years (interquartile range, 2.9-9.2), 5008 participants developed incident OLD (incidence rate, 2.1 per 1000 person-years; 95% CI, 2.1-2.2). In the fully-adjusted model, the HR (95% CI) for incident OLD comparing eosinophil counts of 100- less then 200, 200- less then 300, 300- less then 500 and ≥500 cells·μL-1 to less then 100 cells·μL-1 were 1.07 (1.00-1.15), 1.30 (1.20-1.42), 1.46 (1.33-1.60) and 1.72 (1.51-1.95) (p for trend less then 0.001). These associations were consistent in clinically relevant subgroups, including never, former, and current smokers.In this large longitudinal cohort study, blood eosinophil counts were positively associated with the risk of developing of OLD. Our findings indicate a potential role of eosinophil count as an independent risk factor for developing COPD.Understanding when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged is critical to evaluating our current approach to monitoring novel zoonotic pathogens and understanding the failure of early containment and mitigation efforts for COVID-19. We used a coalescent framework to combine retrospective molecular clock inference with forward epidemiological simulations to determine how long SARS-CoV-2 could have circulated before the time of the most recent common ancestor of all sequenced SARS-CoV-2 genomes. Our results define the period between mid-October and mid-November 2019 as the plausible interval when the first case of SARS-CoV-2 emerged in Hubei province, China. By characterizing the likely dynamics of the virus before it was discovered, we show that more than two-thirds of SARS-CoV-2-like zoonotic events would be self-limited, dying out without igniting a pandemic. Our findings highlight the shortcomings of zoonosis surveillance approaches for detecting highly contagious pathogens with moderate mortality rates.