Background To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health ...Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio OR, 1.14; P = 4 × 10−9 ) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10−8 ). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP . Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10−7 ) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10−6 ). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.
Summary Background The outcome of patients with ruptured abdominal aortic aneurysm (rAAA) varies by country. Study of practice differences might allow the formulation of pathways to improve care. ...Methods We compared data from the Hospital Episode Statistics for England and the Nationwide Inpatient Sample for the USA for patients admitted to hospital with rAAA from 2005 to 2010. Primary outcomes were in-hospital mortality, mortality after intervention, and decision to follow non-corrective treatment. In-hospital mortality and the rate of non-corrective treatment were analysed by binary logistic regression for each health-care system, after adjustment for age, sex, year, and Charlson comorbidity index. Findings The study included 11 799 patients with rAAA in England and 23 838 patients with rAAA in the USA. In-hospital mortality was lower in the USA than in England (53·05% 95% CI 51·26–54·85 vs 65·90%; p<0·0001). Intervention (open or endovascular repair) was offered to a greater proportion of cases in the USA than in England (19 174 80·43% vs 6897 58·45%; p<0·0001) and endovascular repair was more common in the USA than in England (4003 20·88% vs 589 8·54%; p<0·0001). Postintervention mortality was similar in both countries (41·77% for England and 41·65% for USA). These observations persisted in age-matched and sex-matched comparisons. In both countries, reduced mortality was associated with increased use of endovascular repair, increased hospital caseload (volume) for rAAA, high hospital bed capacity, hospitals with teaching status, and admission on a weekday. Interpretation In-hospital survival from rAAA, intervention rates, and uptake of endovascular repair are lower in England than in the USA. In England and the USA, the lowest mortality for rAAA was seen in teaching hospitals with larger bed capacities and doing a greater proportion of cases with endovascular repair. These common factors suggest strategies for improving outcomes for patients with rAAA. Funding None.
Diabetes confers a two times excess risk of cardiovascular disease, yet predicting individual risk remains challenging. The effect of total microvascular disease burden on cardiovascular disease risk ...among individuals with diabetes is unknown.
A population-based cohort of patients with type 2 diabetes from the UK Clinical Practice Research Datalink was studied (n=49 027). We used multivariable Cox models to estimate hazard ratios (HRs) for the primary outcome (the time to first major cardiovascular event, which was a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischaemic stroke) associated with cumulative burden of retinopathy, nephropathy, and peripheral neuropathy among individuals with no history of cardiovascular disease at baseline.
During a median follow-up of 5·5 years, 2822 (5·8%) individuals experienced a primary outcome. After adjustment for established risk factors, significant associations were observed for the primary outcome individually for retinopathy (HR 1·39, 95% CI 1·09-1·76), peripheral neuropathy (1·40, 1·19-1·66), and nephropathy (1·35, 1·15-1·58). For individuals with one, two, or three microvascular disease states versus none, the multivariable-adjusted HRs for the primary outcome were 1·32 (95% CI 1·16-1·50), 1·62 (1·42-1·85), and 1·99 (1·70-2·34), respectively. For the primary outcome, measures of risk discrimination showed significant improvement when microvascular disease burden was added to models. In the overall cohort, the net reclassification index for USA and UK guideline risk strata were 0·036 (95% CI 0·017-0·055, p<0·0001) and 0·038 (0·013-0·060, p<0·0001), respectively.
The cumulative burden of microvascular disease significantly affects the risk of future cardiovascular disease among individuals with type 2 diabetes. Given the prevalence of diabetes globally, further work to understand the mechanisms behind this association and strategies to mitigate this excess risk are warranted.
Circulation Foundation.
Objective Thoracic endovascular aortic repair (TEVAR) of various pathologies has been associated with peri-interventional neurologic complication rates of up to 15%. The objective of this study was ...to determine the influence of the management of the left subclavian artery (LSA) on neurologic complications and to define subgroups that might benefit from LSA revascularization. Methods The Medtronic Thoracic Endovascular Registry (MOTHER; Medtronic, Santa Rosa, Calif), consists of data from five sponsored trials and one institutional series incorporating 1010 patients undergoing TEVAR from 2002 to 2010. Perioperative stroke and spinal cord injury (SCI) rates were described according to the management of the LSA and presenting pathology. Multivariate analysis was performed to determine factors associated with perioperative neurologic complications. Results Of 1002 patients included in the analysis, stroke occurred in 48 (4.8%), and SCI developed in 42 (4.2%) ≤30 days of surgery. The stroke rate was 2.2% in patients with no coverage of the LSA vs 9.1% with coverage alone and 5.1% in patients who underwent LSA revascularization before coverage ( P < .001). This relationship was strongest in the aneurysm group. Coverage of the LSA without revascularization was independently associated with stroke (odds ratio OR, 3.5; 95% confidence interval CI, 1.7-7.1), specifically in the posterior territory (OR, 11.7; 95% CI, 2.5-54.6), as was previous cerebrovascular accident (OR, 7.1; 95% CI, 2.2-23.1; P = .001), whereas a covered LSA was not associated with an increased risk of SCI. Conclusions Coverage of the LSA without revascularization is an important modifiable risk factor for stroke in patients undergoing TEVAR for a thoracic aortic aneurysm. Prior revascularization appears to protect against posterior circulation territory stroke.
Background Endovascular treatments of Stanford type B aortic dissection may help to promote aortic remodeling and reduce the incidence of aortic-related complications. The aim of this study was to ...review published literature describing aortic remodeling after endovascular treatment of aortic dissection. Methods A systematic review of the literature was performed which was compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The type of aortic morphology measurements made and the methods used to make them were characterized. The endpoints of interest were the change in these measurements over time. Results After initial screening, 77 articles were identified; 16 of which met the inclusion criteria. Few studies used three-dimensional reconstruction software and none had validated their measurement protocol. True lumen (TL) and false lumen (FL) diameters, areas, and in some cases volumes were measured. Studies assessed the aorta at a variety of different levels and over different periods of follow-up. Acute dissection patients displayed more consistent degree of remodeling (thoracic FL thrombosis in 80% to 90%) than chronic dissection patients (38% to 91%). Less remodeling was seen below the diaphragm in both groups. Conclusions Aortic remodeling after treatment for dissection is described in a highly heterogeneous manner. Despite this there appears to be a greater degree of complete FL resolution in patients with acute dissection than chronic. Factors such as length of aortic coverage and timing of treatment may explain the variation seen in the chronic dissection group. Consensus-based reporting standards are required to synthesize evidence and inform clinical decisions regarding patient selection and operative timing.
Background Procedural mortality is of paramount importance for patients undergoing elective abdominal aortic aneurysm (AAA) repair. Previous comparative studies have demonstrated international ...differences in the care of ruptured AAA. This study compared the use of endovascular aneurysm repair (EVAR) and in-hospital mortality for elective AAA repair in England and the United States. Methods The English Hospital Episode Statistics and the U.S. Nationwide Inpatient Sample (NIS) were interrogated for elective AAA repair from 2005 to 2010. In-hospital mortality and the use of EVAR were analyzed separately for each health care system, after within-country risk adjustment for age, gender, year, and an accepted national comorbidity index. Results The study included 21,272 patients with AAA in England, of whom 86.61% were male, with median (interquartile range) age of 74 (69-79) years. There were 196,113 AAA patients in the United States, of whom 76.14% were male, with median (interquartile range) age of 73 (67-78) years. In-hospital mortality was greater in England (4.09% vs 1.96 %; P < .01) and EVAR less common (37.33% vs 64.36%; P < .01). These observations persisted in age- and gender-matched comparison. In both countries, lower mortality and greater use of EVAR were seen in centers performing greater numbers of AAA repairs per annum. In England, lower mortality and greater use of EVAR were seen in teaching hospitals with larger bed capacity. Conclusions In-hospital survival and the uptake of EVAR are lower in England than in the United States. In both countries, mortality was lowest in high-caseload centers performing a greater proportion of cases with endovascular repair. These common factors suggest strategies for improving outcomes for patients requiring elective AAA repair.
Introduction Popliteal entrapment syndrome (PES) is a rare but important cause of intermittent claudication in young people. Controversy exists about optimal strategies for diagnosis and management, ...particularly for variants such as functional popliteal entrapment. The aim of this review was to systematically catalog the published English-language literature on PES and to determine if evidence-based guidelines for management could be formulated. Methods An electronic search using the MEDLINE, EMBASE, Cochrane Library, AMED, and CINAHL databases was performed to identify articles about PES published from 1947 to December 2010. The systematic review conformed to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement standards. Prospective studies and retrospective case series with more than five patients with arterial, venous, nerve, and combined neurovascular entrapment were analyzed on a study-by-study narrative basis. Results The search identified 291 articles, and 44 were included. Of these, 30 studies were on popliteal artery entrapment syndrome (PAES). No relationship was found between duration of symptoms and the presence of irreversible arterial injury. Each study used a median of three diagnostic tests (range, 1-6). Arteriography was used in 28 of 30 studies to diagnose PAES, with an estimated mean sensitivity of 97% (range, 85%-100%). Twenty-three studies described arterial reconstructive procedures, with a median failure rate of 27.5% (range, 0%-83%). The proportion of patients asymptomatic after surgery was reported in only 12 of 30 studies, with a median value of 77% (range, 70%-100%). Conclusions A large volume of predominantly retrospective clinical data exists on PES. A subset of studies describe a significant failure rate after surgery, but study quality is insufficient to derive robust conclusions allowing recommendation of any one particular diagnostic modality or operative procedure over another. Improvements in management of this condition are unlikely to result from publication of further retrospective case series, and clinicians should concentrate on prospectively collected data with predefined inclusion criteria, outcome measures, follow-up protocols, and transparent standardized reporting criteria.
This review analyzed the incidence, mechanisms, and risk factors of aortic-related reintervention after endovascular repair of chronic dissections. The systematic review identified 28 studies ...describing 1,249 patients at median 27 months follow-up (range, 10.3 to 64.4). There were six reinterventions, 0.7 ruptures, and 1.2 surgical conversions per 100 patient-years of follow-up. Stent-related reinterventions were more frequent than nonstent related (80.2% vs 19.8%). Distal false lumen perfusion was the most common complication (40.5%). No individual risk factor—treatment timing, disease extent, covered aorta length, or remodelling—was associated with reintervention. Further investigation based on consistent reporting standards is required.
Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and ...allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links ( AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu ), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts.
Background Critical limb ischemia carries a significant risk of morbidity and mortality. The development of scores to predict risk can aid clinical decision making. The Bypass versus Angioplasty in ...Severe Ischaemia of the Leg (BASIL) trial investigators developed a model to predict death, which has not been previously validated. Methods Data were collected in a prospectively maintained database on all patients who underwent angioplasty or arterial bypass for peripheral artery disease in a university hospital between January 2008 and June 2010. The main outcome measures were all-cause mortality and amputation-free survival at 3, 6, 12, and 24 months after the index intervention. The BASIL survival predictor, Finland National Vascular (FINNVASC) registry, and Edifoligide for the Prevention of Infrainguinal Vein Graft Failure (PREVENT) models were applied and receiver-operating characteristic (ROC) curve analysis was used to evaluate their predictive power. Results Data on 342 patients were collected. Patients with isolated iliac disease or claudication were excluded. The 6-, 12-, and 24-month all-cause mortality rates were 11.6%, 17.9%, and 26.8%, respectively. The area under the ROC curve (95% confidence interval) using the BASIL score to predict mortality at 6, 12, and 24 months was 0.700 (0.60-0.80; P < .001), 0.651 (0.56-0.74; P < .003), and 0.681 (0.59-0.74; P < .001), respectively. ROC curve analysis indicated that the performance of the BASIL score in this cohort was comparable to other validated predictive scores. Conclusions The BASIL survival prediction model can moderately predict short-term and medium-term mortality in patients with limb ischemia and may be a useful adjunct to decision making in everyday clinical practice.
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