16 research outputs found

    COVID-19 prevalence and mortality in longer-term care facilities

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    This essay considers the factors that have contributed to very high COVID-19 mortality in longer-term care facilities (LTCFs). We compare the demographic characteristics of LTCF residents with those of community-dwelling older adults, and then we review the evidence regarding prevalence and infection fatality rates (IFRs), including links to frailty and some comorbidities. Finally, we discuss policy measures that could foster the physical and mental health and well-being of LTCF residents in the present context and in potential future pandemics

    A genome-wide association study of the frailty index highlights brain pathways in ageing

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    Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) meta-analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60–70 years) and Swedish TwinGene participants (n = 10,616, 41–87 years). FI calculation was based on 49 or 44 self-reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p < 5*10−8). Many FI-associated loci have established associations with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, one appears to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes expressed in the frontal cortex and hippocampus were significantly downregulated (adjusted p < 0.05). We also used Mendelian randomization to identify modifiable traits and exposures that may affect frailty risk, with a higher educational attainment genetic risk score being associated with a lower degree of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on pathways in the brain

    Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis

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    Background Plasma levels of cell-free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Mechanical ventilation affects systemic inflammation in which lung-protective ventilation attenuates the inflammatory response. The aim was to study the effect of a lung protective ventilator regime on arterial and organ-specific venous blood as well as on trans-organ differences in cf-DNA levels in a porcine post-operative sepsis model. Method One group of anaesthetised, domestic-breed, 9-12 weeks old, pigs were ventilated with protective ventilation (V(T)6 mL x kg(- 1), PEEP 10 cmH(2)O)n = 20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (V(T)10 mL x kg(- 1), PEEP 5 cm H2O)n = 10. Blood samples were taken from four sources: artery, hepatic vein, portal vein and, jugular bulb. A continuous endotoxin infusion at 0.25 mu g x kg(- 1)x h(- 1)for 5 h was started following 2 h of laparotomy, which simulated a surgical procedure. Inflammatory cytokines and cf-DNA in plasma were analysed and trans-organ differences calculated. Results The protective ventilation group had lower levels of cf-DNA in arterial (p = 0.02) and hepatic venous blood (p = 0.03) compared with the controls. Transhepatic differences in cf-DNA were lower in the protective group, compared with the controls (p = 0.03). No differences between the groups were noted as regards the transcerebral, transsplanchnic or the transpulmonary cf-DNA differences. Conclusions Protective ventilation suppresses arterial levels of cf-DNA. The liver seems to be a net contributor to the systemic cf-DNA levels, but this effect is attenuated by protective ventilation
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