The effect of frailty on survival in patients with COVID-19 (COPE) : a multicentre, European, observational cohort study

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Routine Use of Immunosuppressants is Associated with Mortality in Hospitalised Patients with Covid-19

Acknowledgement We acknowledge the dedication, commitment, and sacrifice of the staff from participating centres across UK and Italy, two among the most severely affected countries in Europe. We gratefully acknowledge the contribution of our collaborators, National Institute of Health Research (NIHR), Health Research Authority (HRA) in the UK and Ethics Committee of Policlinico Hospital Modena, which provided rapid approval of COPE study and respective Institutions’ Research and Development Offices and Caldicott Guardians for their assistance and guidance. We also thank COPE Study Sponsor, Cardiff University, Wales, UK.Peer reviewedPublisher PD

Tourist Photographers and the Promotion of Travel: the Polytechnic Touring Association, 1888–1939

The Polytechnic Touring Association (PTA) was a London-based, originally philanthropic turned commercial travel firm whose historical origins coincided with the arrival of the Kodak camera in 1888 – thus, of popular (tourist) photography. This article examines the PTA’s changing relationship with tourist photographers, and how this influenced the company’s understanding of what role photography could play in promoting the tours, in the late nineteenth and early twenty century. This inquiry is advanced on the basis of the observation that, during this time, the PTA’s passage from viewing tourists as citizens to educate, to customers to please, paralleled the move from using photography-based images to mixed media. Such a development was certainly a response to unprecedented market demands; this article argues that it should also be considered in relation to the widening of photographic perceptions engendered by the democratization of the medium, to which the PTA responded, first as educator, then as service provider. In doing so, the article raises several questions about the shifting relationship between “high”, or established, and “low”, or emerging, forms of culture, as mass photography and the mass marketing of tourism developed

The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study

Background The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. Methods This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). Findings Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61–83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5–8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00–2·41) for CFS 3–4, 1·83 (1·15–2·91) for CFS 5–6, and 2·39 (1·50–3·81) for CFS 7–9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63–2·38) for CFS 3–4, 1·62 (0·81–3·26) for CFS 5–6, and 3·12 (1·56–6·24) for CFS 7–9. Interpretation In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation

Publisher Copyright: © 2022 The AuthorsBackground: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). Results: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10−6) in older children and had methylation differences in the same direction. Conclusions: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.Peer reviewe

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe