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

Editor's choice - Incidence of stroke following thoracic endovascular aortic repair for descending aortic aneurysm: a systematic review of the literature with meta-analysis.

OBJECTIVE: Stroke is an increasingly recognised complication following thoracic endovascular aortic repair (TEVAR). The aim of this study was to systematically synthesise the published data on perioperative stroke incidence during TEVAR for patients with descending thoracic aneurysmal disease and to assess the impact of left subclavian artery (LSA) coverage on stroke incidence. METHODS: A systematic review of English and German articles on perioperative (in-hospital or 30 day) stroke incidence following TEVAR for descending aortic aneurysm was performed, including studies with ≥50 cases, using MEDLINE and EMBASE (2005-2015). The pooled prevalence of perioperative stroke with 95% CI was estimated using random effect analysis. Heterogeneity was examined using I(2) statistic. RESULTS: Of 215 studies identified, 10 were considered suitable for inclusion. The included studies enrolled a total of 2594 persons (61% male) between 1997 and 2014 with a mean weighted age of 71.8 (95% CI 71.1-73.6) years. The pooled prevalence for stroke was 4.1% (95% CI 2.9-5.5) with moderate heterogeneity between studies (I(2) = 49.8%, p = .04). Five studies reported stroke incidences stratified by the management of the LSA, that is uncovered versus covered and revascularised versus covered and not-revascularised. In cases where the LSA remained uncovered, the pooled stroke incidence was 3.2% (95% CI 1.0-6.5). There was, however, an indication that stroke incidence increased following LSA coverage, to 5.3% (95% CI 2.6-8.6) in those with a revascularisation and 8.0% (95% CI 4.1-12.9) in those without revascularisation. CONCLUSION: Stroke incidence is an important morbidity after TEVAR, and probably increases if the LSA is covered during the procedure, particularly in those without revascularisation

Editor's Choice – Sex Specific Differences in the Management of Descending Thoracic Aortic Aneurysms: Systematic Review with Meta-Analysis

Objectives: To assess sex-specific differences in 30-day mortality, length of hospital stay and adverse neurological events following repair of intact degenerative descending thoracic aortic aneurysms, by either endovascular (TEVAR) or open repair. Data Sources: Medline, Embase and CENTRAL databases searched from 2005-2019 using ProQuest Dialog™. Review methods: The reviews were registered in PROSPERO (CRD42017020026) and performed according to PRISMA guidelines. The primary outcome was 30-day mortality with secondary outcomes of length of hospital stay and adverse neurological events. Forest plots with random effects meta-analysis to provide odds ratios (OR) were used for primary assessment. Results: For TEVAR, a total of seven studies were identified including 2758 women and 4674 men; of these six were eligible for the primary outcome of 30-day mortality including 1756 women and 2619 men. There were 94/1756 deaths in women and 82/2619 deaths in men, yielding a pooled 30-day mortality of 5% (95% c.i. 3 to 7) in women and 3% (95% c.i. 2 to 4) in men (OR 1.75 [95%CI 1.29; 2.38]). Length of hospital stay was longer in women, with standardised mean difference 0.3 days [95%CI 0.14; 0.47] (6 studies): meta-regression analysis did not identify the slightly older age of women as significant factor in these differences. Stroke rate was not different between the sexes. For open repair only a single study, with national coverage, was identified that reported 30-day mortality, which was similar in men and women. Conclusion: In the management of intact degenerative descending thoracic aortic aneurysms, 30-day mortality following TEVAR appears to be much higher in women than men with no reasons for this difference identified. For open repair however, there is a lack of contemporary evidence due to insufficient recent data

Women assessed for intact abdominal aortic aneurysm repair fare worse than men: systematic reviews of morphological suitability for endovascular repair, non-intervention rates and operative mortality

Objective: To systematically quantify the differences in outcomes between men and women being assessed for repair of intact abdominal aortic aneurysm (AAA) in contemporary data (2000 or later). Methods: Three systematic reviews were undertaken, according to PRISMA guidelines of studies reporting separately for men and women the proportion morphologically suitable (within Manufacturers’ Instructions for Use) for endovascular repair (EVAR), non-intervention rates, and 30-day mortality after intact aneurysm repair. The minimum numbers for studies in each review were based on inclusion of 20, 20 and 50 women, respectively. Studies (randomised, cohort or cross-sectional) were identified by searching MEDLINE, Embase, CENTRAL and other sources until 2nd September 2016 and quality assessed using the Newcastle–Ottawa scoring system. Results were combined across studies by random-effects meta-analysis. The reviews are registered in PROSPERO: CRD42016043227. Results: Five studies evaluated the morphological eligibility for EVAR (1507 men, 400 women). The overall proportion of women eligible for EVAR was much lower than in men, 34% versus 54%, odds ratio 0.44 [95%CI 0.32,0.62]. Four single centre studies reported non-intervention rates (1365 men, 247 women). The overall non-intervention rates were higher in women than men, 34% versus 19%, odds ratio 2.27 [95%CI 1.21,4.23]. The review of 30-day mortality included nine studies (52018 men, 10076 women). The overall estimate for EVAR was higher in women than men: 2.3% versus 1.4%, odds ratio 1.67 [95%CI 1.38,2.04]. The overall estimate for open repair also was higher in women: 5.4% versus 2.8% in men, odds ratio 1.76 [95%CI 1.35,2.30]. Interpretation: A smaller proportion of women are eligible for EVAR, a higher proportion of women are not offered intervention, and operative mortality was much higher in women for both EVAR and open repair. The management of AAA in women needs improvement

Hospital trends of admissions and procedures for acute leg ischaemia in England, 2000-2011.

INTRODUCTION Acute leg ischaemia (ALI) is a common vascular emergency for which new minimally invasive treatment options were introduced in the 1990s. The aim of this study was to determine recent hospital trends for ALI in England and to assess whether the introduction of the new treatment modalities had affected management. METHODS Routine hospital data covering ALI were provided by Hospital Episode Statistics for the years 2000 to 2011 and mortality data were obtained from the Office for National Statistics. All data were age standardised, reported per 100,000 of the population, and stratified by age band (60-74 years and ≥75 years) and sex. RESULTS Hospital admissions have risen significantly from 60.3 to 94.3 per 100,000 of the population, with an average annual increase of 6.2% since 2003 (p<0.001). The rise was greater in the older age group (from 79.9 to 134.4 vs 49.3 to 73.0) and yet procedures for ALI have shown a significant decrease since 2000 from 14.3 to 12.4 per 100,000 (p=0.013), independent of age and sex. Open embolectomy of the femoral artery remains the most common procedure and the proportion of endovascular interventions showed only a small increase. Only a few deaths were attributed to ALI (range: 95-150 deaths per year). CONCLUSIONS Hospital workload for ALI has increased, particularly since 2003, but this trend does not appear to have translated into increased endovascular or surgical activity