Реферат
The increase in life expectancy has also been accompanied by an increase in the use of medication to treat chronic diseases. Polypharmacy is associated with medication-related problems such as the increase in the anticholinergic burden. Older people are more susceptible to anticholinergic effects on the central nervous system and this, in turn, may be related to cognitive impairment. In this paper, we develop an updated anticholinergic burden scale, the CRIDECO Anticholinergic Load Scale (CALS) via a systematic review of the literature and compare it with the currently most used Anticholinergic Burden Scale (ACB). Our new scale includes 217 different drugs with anticholinergic properties, 129 more than the ACB. Given the effect that anticholinergic medications have on cognitive performance, we then used both scales to investigate the relationship between anticholinergic burden and cognitive impairment in adult Spanish subjects with subjective memory complaint. In our population, we observed an association between cognitive impairment and the anticholinergic burden when measured by the new CALS, but not when the ACB was applied. The use of a more comprehensive and upgraded scale will allow better discrimination of the risk associated with the use of anticholinergic medications on cognitive impairment. CALS can help raise awareness among clinicians of the problems associated with the use of medications, or combinations of them, with large anticholinergic effect, and promote a better personalized pharmacological approach for each patient.
Реферат
BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. METHODS: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. FINDINGS: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. INTERPRETATION: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2. FUNDING: The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.