Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis

Background Prognosis for women with abdominal aortic aneurysm might be worse than the prognosis for men. We aimed to systematically quantify the differences in outcomes between men and women being assessed for repair of intact abdominal aortic aneurysm using data from study periods after the year 2000. Methods In these systematic reviews and meta-analysis, we identified studies (randomised, cohort, or cross-sectional) by searching MEDLINE, Embase, CENTRAL, and grey literature published between Jan 1, 2005, and Sept 2, 2016, for two systematic reviews and Jan 1, 2009, and Sept 2, 2016, for one systematic review. Studies were included if they were of both men and women, with data presented for each sex separately, with abdominal aortic aneurysms being assessed for aneurysm repair by either endovascular repair (EVAR) or open repair. We conducted three reviews based on whether studies reported the proportion morphologically suitable (within manufacturers' instructions for use) for EVAR (EVAR suitability review), non-intervention rates (non-intervention review), and 30-day mortality (operative mortality review) after intact aneurysm repair. Studies had to include at least 20 women (for the EVAR suitability review), 20 women (for the non-intervention review), and 50 women (for the operative mortality review). Studies were excluded if they were review articles, editorials, letters, or case reports. For the operative review, studies were also excluded if they only provided hazard ratios or only reported in-hospital mortality. We assessed the quality of the studies using the Newcastle–Ottawa scoring system, and contacted authors for the provision of additional data if needed. We combined results across studies by random-effects meta-analysis. This study is registered with PROSPERO, number CRD42016043227. Findings Five studies assessed the morphological eligibility for EVAR (1507 men, 400 women). The overall pooled proportion of women eligible (34%) for EVAR was lower than it was in men (54%; odds ratio [OR] 0·44, 95% CI 0·32–0·62). Four single-centre studies reported non-intervention rates (1365 men, 247 women). The overall pooled non-intervention rates were higher in women (34%) than men (19%; OR 2·27, 95% CI 1·21–4·23). The review of 30-day mortality included nine studies (52 018 men, 11 076 women). The overall pooled estimate for EVAR was higher in women (2·3%) than in men (1·4%; OR 1·67, 95% CI 1·38–2·04). The overall estimate for open repair also was higher in women (5·4%) than in men (2·8%; OR 1·76, 95% CI 1·35–2·30). Interpretation Compared with men, a smaller proportion of women are eligible for EVAR, a higher proportion of women are not offered intervention, and operative mortality is much higher in women for both EVAR and open repair. The management of abdominal aortic aneurysm in women needs improvement.This project was funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project number 14/179/01). Work done at the University of Cambridge was additionally funded by the Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194), and the National Institute for Health Research; Cambridge Biomedical Research Centre)

Equal pay by gender and by nationality: a comparative analysis of Switzerland's unequal equal pay policy regimes across time

What explains the adoption of two different policies on equal pay by gender (EPG) and by nationality (EPN) in Switzerland? And why is the liberal, litigation-based, equal pay policy regime set up by the Gender Equality Act of 1996 much less effective than the neocorporatist ‘accompanying measures' to the Bilateral European Union-Switzerland Agreement on Free Movement of Persons adopted in 1999 to ensure equal pay for workers of different national origins? The formation of two different policy regimes cannot be explained by different levels of political will. Equally, different ‘varieties of capitalism' cannot explain the setup of the two different equal pay policy regimes within the very same country. Instead, our qualitative comparative analysis across time suggests that the differences can be best explained by a particular constellation of attributes, namely the use of different policy frames—i.e. ‘anti-discrimination' in the EPG and ‘unfair competition' in the EPN case—and the different setting of interest politics epitomised by the opposite stances adopted by Switzerland's employer associations in the two case

Corrigendum to 'Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections' [European Journal of Vascular & Endovascular Surgery 59/3 (2020) 339-384]

peer reviewe

Association of ultra-rare coding variants with genetic generalized epilepsy: A case\u2013control whole exome sequencing study

Objective: We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set out to compare the association of genes independently with familial and sporadic GGE. Methods: We performed a case\u2013control whole exome sequencing study in unrelated individuals of European descent diagnosed with GGE (previously recruited and sequenced through multiple international collaborations) and ancestry-matched controls. The association of ultra-rare variants (URVs; in 18 834 protein-coding genes) with epilepsy was examined in 1928 individuals with GGE (vs. 8578 controls), then separately in 945 individuals with familial GGE (vs. 8626 controls), and finally in 1005 individuals with sporadic GGE (vs. 8621 controls). We additionally examined the association of URVs with familial and sporadic GGE in two gene sets important for inhibitory signaling (19 genes encoding \u3b3-aminobutyric acid type A [GABAA] receptors, 113 genes representing the GABAergic pathway). Results: GABRG2 was associated with GGE (p = 1.8  7 10 125), approaching study-wide significance in familial GGE (p = 3.0  7 10 126), whereas no gene approached a significant association with sporadic GGE. Deleterious URVs in the most intolerant subgenic regions in genes encoding GABAA receptors were associated with familial GGE (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 1.9\u20137.8, false discovery rate [FDR]-adjusted p =.0024), whereas their association with sporadic GGE had marginally lower odds (OR = 3.1, 95% CI = 1.3\u20136.7, FDR-adjusted p =.022). URVs in GABAergic pathway genes were associated with familial GGE (OR = 1.8, 95% CI = 1.3\u20132.5, FDR-adjusted p =.0024) but not with sporadic GGE (OR = 1.3, 95% CI =.9\u20131.9, FDR-adjusted p =.19). Significance: URVs in GABRG2 are likely an important risk factor for familial GGE. The association of gene sets of GABAergic signaling with familial GGE is more prominent than with sporadic GGE

Draft Genome Sequencing of Giardia intestinalis Assemblage B Isolate GS: Is Human Giardiasis Caused by Two Different Species?

Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16× coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species

Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox–Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient–parent trios that were generally prescreened for rare metabolic disorders. In the current sample, our rare variant transmission disequilibrium test did not identify individual genes with significantly distorted transmission over expectation after correcting for the multiple tests. While the rare variant transmission disequilibrium test did not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population