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o 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. 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). MYF-01-37 ic50 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.