Search

Background: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea in Europe. Despite increased focus, its incidence and severity are increasing in many European countries., Aim: We developed a series of consensus statements to identify unmet clinical needs in the recognition and management of CDI., Methods: A consortium of European experts prepared a series of 29 statements representing their collective views on the diagnosis and management of CDI in Europe. The statements were grouped into the following six broad themes: diagnosis; definitions of severity; treatment failure, recurrence and its consequences; infection prevention and control interventions; education and antimicrobial stewardship; and National CDI clinical guidance and policy. These statements were reviewed using questionnaires by 1047 clinicians involved in managing CDI, who indicated their level of agreement with each statement., Findings: Levels of agreement exceeded the 66% threshold for consensus for 27 out of 29 statements (93.1%), indicating strong support. Variance between countries and specialties was analysed and showed strong alignment with the overall consensus scores., Conclusion: Based on the consensus scores of the respondent group, recommendations are suggested for the further development of CDI services in order to reduce transmission and recurrence and to ensure that appropriate diagnosis and treatment strategies are applied across all healthcare settings., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Data on the outcome of young patients after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are scarce. Data on 2,209 consecutive patients aged≤50 years who underwent CABG or PCI were retrospectively collected from 15 European institutions. PCI and CABG had similar 30-day mortality rates (0.8% vs 1.4%, p=0.27), late survival (at 5 years, 97.8% vs 94.9%, p=0.082), and freedom from stroke (at 5 years, 98.0% and 98.0%, p=0.731). PCI was associated with significantly lower freedom from major adverse cardiac and cerebrovascular events (at 5 years, 73.9% vs 85.0%, p<0.0001), repeat revascularization (at 5 years, 77.6% vs 92.5%, p<0.0001), and myocardial infarction (at 5 years, 89.9% vs 96.6%, p<0.0001) compared with CABG. These findings were confirmed in propensity score-adjusted and matched analyses. Freedom from major adverse cardiac and cerebrovascular events after PCI was particularly low in diabetics (at 5 years, 58.0% vs 75.9%, p<0.0001) and in patients with multivessel disease (at 5 years, 63.6% vs 85.1%, p<0.0001). PCI in patients with ST elevation myocardial infarction was associated with significantly better 5-year survival (97.5% vs 88.8%, p=0.001), which was driven by its lower 30-day mortality rate (1.5% vs 6.0%, p=0.017). In conclusion, patients aged≤50 years have an excellent immediate outcome after either PCI or CABG with similar long-term survival when used according to the current clinical practice. PCI was associated with significantly lower freedom from myocardial infarction and repeat revascularization., (Copyright © 2014 Elsevier Inc. All rights reserved.)

3% of the population develops saccular intracranial aneurysms (sIAs), a complex trait, with a sporadic and a familial form. Subarachnoid hemorrhage from sIA (sIA-SAH) is a devastating form of stroke. Certain rare genetic variants are enriched in the Finns, a population isolate with a small founder population and bottleneck events. As the sIA-SAH incidence in Finland is >2× increased, such variants may associate with sIA in the Finnish population. We tested 9.4 million variants for association in 760 Finnish sIA patients (enriched for familial sIA), and in 2,513 matched controls with case-control status and with the number of sIAs. The most promising loci (p<5E-6) were replicated in 858 Finnish sIA patients and 4,048 controls. The frequencies and effect sizes of the replicated variants were compared to a continental European population using 717 Dutch cases and 3,004 controls. We discovered four new high-risk loci with low frequency lead variants. Three were associated with the case-control status: 2q23.3 (MAF 2.1%, OR 1.89, p 1.42×10-9); 5q31.3 (MAF 2.7%, OR 1.66, p 3.17×10-8); 6q24.2 (MAF 2.6%, OR 1.87, p 1.87×10-11) and one with the number of sIAs: 7p22.1 (MAF 3.3%, RR 1.59, p 6.08×-9). Two of the associations (5q31.3, 6q24.2) replicated in the Dutch sample. The 7p22.1 locus was strongly differentiated; the lead variant was more frequent in Finland (4.6%) than in the Netherlands (0.3%). Additionally, we replicated a previously inconclusive locus on 2q33.1 in all samples tested (OR 1.27, p 1.87×10-12). The five loci explain 2.1% of the sIA heritability in Finland, and may relate to, but not explain, the increased incidence of sIA-SAH in Finland. This study illustrates the utility of population isolates, familial enrichment, dense genotype imputation and alternate phenotyping in search for variants associated with complex diseases.

This study was planned to identify the determinants of outcome after coronary artery bypass (CABG) in young patients. Data on 592 patients aged ≤50 years who underwent CABG from 9 European institutions were collected retrospectively. Twenty-eight percent of patients received at least 2 arterial grafts. Clopidogrel was used at discharge in 16.2% and statins in 67.2% of patients. Freedom from major adverse cardiac and cerebrovascular events at 1, 3, and 5 years was 93.8%, 90.1%, and 85.0%; survival rate was 98.3%, 96.3%, and 94.9%; freedom from myocardial infarction was 96.3%, 95.1%, and 92.5%; and freedom from repeat revascularization was 96.3%, 95.1%, and 92.5%, respectively. Neither types of grafts nor medication at discharge had any impact on the late outcome. Age <40 years (relative risk [RR] 2.19, 95% confidence interval [CI] 1.17 to 4.11), diabetes (RR 1.71, 95% CI 1.02 to 2.88), estimated glomerular filtration rate <60 ml/min/1.73 m(2) (RR 2.44, 95% CI 1.26 to 4.72), non-ST-elevation myocardial infarction/ST-elevation myocardial infarction (RR 2.12, 95% CI 1.27 to 3.55), emergency procedure (RR 2.34, 95% CI 1.13 to 4.88), and left ventricular ejection fraction <30% (RR 3.18, 95% CI 1.41 to 7.16) were independent predictors of major adverse cardiac and cerebrovascular events. Patients with left ventricular ejection fraction <30% had a particularly poor survival rate (at 5 years 67.7% vs 96.1%; adjusted analysis RR 14.01, 95% CI 5.16 to 38.03). Poor left ventricular function, myocardial infarction, diabetes, renal failure, and age <40 years are major determinants of late outcome after CABG in young patients. In conclusion, data from this real-world registry indicate that multiple arterial grafts and statin treatment are largely underutilized in these patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The global prevalence of obesity has increased significantly in recent decades, mainly due to excess calorie intake and increasingly sedentary lifestyle. Here, we test the association between obesity measured by body mass index (BMI) and one of the best-known genetic variants showing strong selective pressure: the functional variant in the cis-regulatory element of the lactase gene. We tested this variant since it is presumed to provide nutritional advantage in specific physical and cultural environments. We genetically defined lactase persistence (LP) in 31 720 individuals from eight European population-based studies and one family study by genotyping or imputing the European LP variant (rs4988235). We performed a meta-analysis by pooling the beta-coefficient estimates of the relationship between rs4988235 and BMI from the nine studies and found that the carriers of the allele responsible for LP among Europeans showed higher BMI (P = 7.9 x 10(-5)). Since this locus has been shown to be prone to population stratification, we paid special attention to reveal any population substructure which might be responsible for the association signal. The best evidence of exclusion of stratification came from the Dutch family sample which is robust for stratification. In this study, we highlight issues in model selection in the genome-wide association studies and problems in imputation of these special genomic regions.