Avoidance in nonepileptic attack disorder:A systematic review and meta-analyses

Background Avoidance is the active process of trying to escape from or not experience situations, places, thoughts, or feelings. This can be done through behavioral or cognitive strategies, or more broadly, a combination of both, utilized in an attempt to disengage from private experiences referred to as experiential avoidance (EA). Avoidance is considered important in the development and maintenance of nonepileptic attack disorder (NEAD). This review aimed to understand avoidance in NEAD and evaluate its role as a contributory factor. Methods Fourteen articles were identified by searching Cumulative Index to Nursing and Allied Health (CINAHL), MEDLINE Complete, PsycINFO, and EMBASE and were combined in a narrative synthesis. Six of these articles were included in a meta-analysis comparing levels of EA for individuals with NEAD and healthy controls (HC), and four were included in a meta-analysis comparing EA in NEAD to epilepsy comparisons (EC). Conclusions Experiential avoidance appears to be a strategy that is used by a high proportion of the population with NEAD. The group with NEAD utilized significantly more avoidance compared with both the HC and EC. However, further research is needed to understand the extent and types of avoidance that are relevant

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice